Journal of Histopathology and Cytopathology

Official Organ of Bangladesh Academy of Pathology

Vol 6, No 2, July 2022

Front Cover


Editorial Board


Reporting Papillary Lesions of the Breast on Core Biopsies
Baqui MN
Page 71

Original Contributions
p16 Expression Pattern in Different Morphological Variants of Cervical Adenocarcinoma in Bangladeshi Women
Khatun S, Akhter S, Kamal M, Islam N,, Sultana S, Yusuf F
Page 72-80

Relationship between AMACR (Alpha Methyl Acyl CoA Racemase/P504S) Staining Intensity and Histopathological Gleason Grading of Prostatic Adenocarcinoma
Haque S, Aymon NN, Ferdous JN, Islam Z, Ripa SP, Dey S, Mudi N
Page 81-87

The Milan System for Reporting Salivary Gland Cytopathology with Histologic follow – up: A 10-year Multi-institutional Study in India
Mondal SK, Bhattacharya S, Biswas S, Sinha MG
Page 88-96

Case Reports
Gliomatosis Peritonei Combined with Mature Cystic Teratoma: A Case Report
Rahman DA, Begum A
Page 97-101

Renal Papillary Adenoma, an Incidental Finding in the Background of Chronic Calculous Pyelonephritis: A Case Report
Habib S, Sermin N
Page 102-108

Information for contributors
Page 109

JHC 2022 Jan Vol 6 N 1

Journal of Histopathology and Cytopathology

Official Organ of Bangladesh Academy of Pathology

Vol 6, No 1, January 2022

Front Cover

Editorial Board


Correspondence and Price

Sl No Article Title Page
1 Reporting Standardization in Pathology
Papry A
  Original Contributions  
2 Role of Nerve Bundle Morphometry in Diagnosis of Hirschsprung Disease
Islam T, Banu SG,Dey BP,Rahman MM, Rahman P,Shabnam US, Shiraj-Um-Mahmuda S

3 Detection of Epstein Barr Virus in Nasopharyngeal Carcinoma in Bangladeshi Patients: A Molecular and Pathological Study
Islam F, Kamal M, Habib S

4 Identification of Atypical Epithelial Proliferation in Fallopian Tube in Association with Ovarian Serous Carcinoma
Sultana S, Akhter S, Rahman DA,  Islam N,  Mehjabin M,  Khatun S,  Yusuf F

5 Cytological Patterns of Cervical Papanicolaou Smear at Tertiary Hospital– A Retrospective Study
Ansari M,   Khan AH,  Hossain S, Chowdhury MS,  Khanom F

6 Expression of P63 and AMACR in Benign and Malignant Lesions of Prostate
Haque S, Islam N, Kabir E, Shilpi HR, Begum S, Sharmin L, Jahan N

Case Reports
7 Multilocular Cystic Nephroma: A Case Report in an Adult Patient
Islam F, Begum A, Kamal M

8 Primary Adenoid Cystic Carcinoma of the Ovary: A Rare Case Report
Rahman MZ, Mahmud R, Siddiqui SR, Das NC

9 Co-existent Caecal Adenocarcinoma and Tuberculosis: A Rare Case Report
Rahman DA, Rabby JE, Saadat MA

10 Information for Contributors

Journal of Histopathology and Cytopathology 2020, July

Journal of Histopathology and Cytopathology

Official Organ of Bangladesh Academy of Pathology

Vol 4, No 2, July 2020

Front Cover PDF

Index/Contents PDF

Inside Back cover PDF


Sl No Article Title Page no
1 Histopathological Findings in Fatal COVID-19 Infections
Talukder SI
  Original Contributions  
2 Intratumoral and Peritumoral Angiogenic and Lymphangiogenic Microvessel Density in Invasive Breast Carcinoma and their Correlation with Lymph Node Metastasis
Mehjabin M,Asaduzzaman, Chakravarty S,Hassan MI, Munmun UK,Islam N,Talukder AS, Kamal M
3 Immunohistochemical Analysis and Molecular Subtyping of Breast Cancer
Sharmin S,  Ambiya AS,  Hussain M, Rima FAPDF
4 Diagnosis of Hirschsprung Disease by Frozen Section Biopsy Using Routine Hematoxylin-Eosin (HE) Stain: A Year’s Study
Banu SG, Islam T
5 Histomorphology of Gastroesophageal Junction Lesions (GEJ) and their Malignant Potential in Gastroesophageal Reflux Disease (GERD): A Study of 145 Cases in a Tertiary Level Hospital in Bangladesh
Zabin SG, Dewan RK, Jinnah SA, Jeba R, Sultana T, Rahman LY, Khan ZB
6 E-Cadherin Expression in Transitional Cell Carcinoma of the Urinary Bladder and its Correlation with Histopathological Grade and Tumour Stage
Quruni MO, Saha MK, Afrin SS, Hossain MS, Shaheen N, Dewan RK
7 Extracellular Matrix Metalloproteinase Inducer (EMMPRIN/CD147) Expression and its Correlation with Progression of Oral Squamous Cell Carcinoma
Saha MK,Quruni MO, Afrin SS, Hossain MS,Mahmud  F,  Mahmud SA, Jinnah MA, Dewan MR
Review Article
8 The Many Faces of Focal Segmental Glomerulosclerosis: A Review
  Case Reports  
9 Primary Malignant Melanoma of the Breast: A Case Report
Sadaf A, Hossain MI, Sultana N, Khan AS
10 Information for Contributors


Information for Contributors

Information for Contributors


General Information

The Journal of Histopathology and Cytopathology (JHC) aims in our understanding of the pathophysiological and pathogenetic mechanisms of human disease by publishing original papers, review articles, case reports and short communications related to basic and translational fields in pathology. It serves as bridges between basic biomedical science and clinical medicine with particular emphasis on, but is not restricted to, tissue based studies only. It is published twice a year as the Journal Committee of the Bangladesh Academy of Pathology.

Manuscript Preparation.

Manuscripts should be prepared in MS Word format in accordance with The Uniform Requirements for Manuscripts Submitted to Biomedical Journals

(see http://www.icmje.org). All pages of the manuscript should be double-spaced and numbered consecutively beginning with the Title page.  Each of the following sections should begin on separate pages: Title,  Name and affiliation of authors, Abstract and Keywords, Text, Acknowledgements, References, individual Tables and legends.  Reformatting of the accepted papers may be needed according to the Journal specifications.

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The title page should include (i) type of publication (original, review, case report etc.) (ii) the complete title of the article (iii) authors’ name in abbreviation  (iv) list of authors including full name, highest degree, signature, designation and institutional affiliation and (v) name, mailing address, email and telephone/mobile number of author responsible for correspondence.


It should begin with full title of the article. Do not write authors name in the abstract page. The abstracts should not be more than 200 words. The abstract should state the purpose of the study or investigations, basic procedures, main findings and principal conclusion. Three to ten keywords may be provided below the abstract using terms from the Medical Subject Headings (Index Medicus, NLM, USA). Abbreviations and citations should be avoided.


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References should conform to the style of the Journal.

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Journals: van Riel D, Leijten LM, Kochs G, Osterhaus AD, Kuiken T: Decrease of Virus Receptors during Highly Pathogenic H5N1 Virus Infection in Humans and Other Mammals. Am J Pathol 2013, 183:1382-1389

 Electronic Journals: Moher D, Liberati A, Tetzlaff J, Altman DG, The PRISMA Group: Preferred Reporting Items for Systematic Reviews and Meta-Analyses: The PRISMA Statement. PLoS Med 2009, 6:e1000097. http://dx.doi.org/10.1371/journal.pmed.1000097

 Books: Frosch MP: Central Nervous System. Robbins Basic Pathology, 9th Edition. Edited by Kumar V, Abbas AK, Aster JC. Philadelphia, PA, Saunders, 2012, pp. 811-850

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On receipt, manuscripts are assessed by the Editor-in-Chief, to one Associate Editor. The Reviewers’ and Associate Editor’s views are used by the Editor-in-Chief (or a Senior Editor) in reaching a decision, usually within three weeks of submission.

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Following the title page(s), the next page should carry an unstructured prose abstract of 300 words or less. It should clearly convey the purposes of the study, and the main procedures, findings and conclusions. It should be understandable without reference to the rest of the paper, and contain no citation to references in the reference list. Only standard abbreviations as listed below are permitted.

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 Manuscript structure

Research articles are divided into sections with the headings: Abstract, Introduction, Methods, Results and Discussion. Long articles may need subheadings (especially within the Results and Discussion) to clarify their content. The sections should not be numbered. Other types of articles, such as reviews and commentaries, still need a title and abstract and should adhere as closely as possible to these guidelines.

Epidermal Nevus with Epidermolytic Hyperkeratosis: A Case Report

Epidermal Nevus with Epidermolytic Hyperkeratosis: A Case Report


*Fatima K,1 Banu SG,2 Kamal M3


  1. *Dr. Kaniz Fatima, Resident, Phase-B, Department of Pathology, Bangabandhu Sheikh Mujib Medical University (BSMMU).joty2005.kfz@gmail.com
  2. Sultana Gulshana Banu, Associate Professor, Department of Pathology, Bangabandhu Sheikh Mujib Medical University (BSMMU).
  3. Mohammed Kamal, Professor, Department of Pathology, Bangabandhu Sheikh Mujib Medical University (BSMMU).





Epidermal nevus has various histological patterns. Epidermal nevus having features of epidermolytic hyperkeratosis is a rare condition. This lesion is clinically indistinguishable from other epidermal nevi but shows characteristic histological features. Diagnosis of this entity is important management. Epidermolytic hyperkeratosis is an autosomal dominant disease. Offspring of these patients may have generalized epidermolytic hyperkeratosis. Here we present a case of 12 years old boy with Epidermal nevus with epidermolytic hyperkeratosis, which is a rare entity.

[Journal of Histopathology and Cytopathology, 2020 Jan; 4 (1):65-69]

 Keywords: Epidermal nevus, Epidermolytic hyperkeratosis, Generalized epidermolytic hyperkeratosis, Line of Blaschko.


Epidermal nevus comprises a heterogenous group of diseases. It is a congenital non-inflammatory cutaneous hamartoma. It may occur sporadically or as a part of several syndromes. The condition affects 1 in 1000 people in the world.1 Histologically, epidermal nevi are composed of keratinocytes, apocrine glands, eccrine glands, sebaceous glands or other components of pilosebaceous unit. Epidermal nevi are traditionally asymptomatic. Small number of cases of epidermal nevi show histologic features of epidermolysis hyperkeratosis. Epidermolytic hyperkeratosis has been observed in variety of benign and malignant skin condition or hereditary disorders. Epidermal nevus with epidermolysis hyperkeratosis has a significant clinical importance. This patient carries the risk of parenting a child of gerneralizedepidermolytichyperkeratosis.2 We report a case of epidermal nevus showing epidermolytic hyperkeratosis in a 12 year old boy for the rarity of the entity.

 Case report

A 12 year old boy of a non-consanguineous parentage, presented with non-pruritic, dark coloured elevated skin eruptions since birth. The lesion was first observed over the dorsum of right foot. After that lesions gradually appeared in front of leg and thigh, lower abdomen and flexor aspect of both forearm. Lesions were not related with any seasonal variation. Patient had a normal birth history and developmental milestones. Right sided extremities were more involved than left side.Examination revealed numerous hyperpigmented warty papules distributed in both extremities and lower abdomen (Figure. 1 and 2).  Hair, nails and oral mucosa were normal. Other system examination revealed no abnormality. No laboratory investigation was done.

Clinically it was diagnosised as Linear verrucous epidermal nevus. For histopathological examination 3 mm punch biopsy was taken from right foot. Histological examination revealed hyperkeratosis, acanthosis, papillomatosis, elongated rete ridges. The dermis revealed mild perivascular infiltration of chronic inflammatory cells.Some foci also revealed perinuclear vacuolization of the keratinocytes in spinous and granular layers, and increased number of keratohyalin granules in the stratum granulosum (Figure 3, 4 and 5).  So, histologically it was diagnosed as epidermal nevus with epidermolytic hyperkeratosis.


Epidermal nevus is hamartoma of skin, occurs due to over growth of epidermis. It arises from embryonic ectoderm as a result of mosaic postzygotic mutations. Lesions are present at birth in about half of the patients or may develop early in childhood. Depending on the affected component of the epidermis epidermal nevus can be divided into two types: keratinocytic or non organoidand organoid type.3 Keratinocytic epidermal nevus is the most common type of epidermal nevus. It occurs due to overgrowth of keratinocytes. Different varients of keratinocytic epidermal nevus are seen, such as linear epidermal nevus, hard nevus of Unna, soft epidermal nevus and nevus verrucosus etc.1 On the other hand organoid type shows predominantly another component of skin.4 Epidermal nevus occurs as a result of activated genetic mutation in FGFR-3, HRAS or PIK3CA genes. FOXN1 is highly expressed in these lesions.1 Most common pattern of keratinocytic nevus is linear epidermal nevus. The lesions are verrucous, skin-coloured dirty gray or brown coloured papule, which coalesce to form serpiginious plaques. They follow the line of Blaschko. These lines are thought to be representative pathways of epidermal cell migration and proliferation during development of fetus.5

Linear epidermal nevus may be either localized or systematized. In localized type, only one linear lesion is present and lesion is confined to one side of the body. Common sites are head, trunk and extremities. In systematized type there are many parallel linear lesions are seen. They may be unilateral or bilateral.

Localized and more commonly systematized linear epidermal nevus may be associated with skeletal deformity and CNS deficiency.6 Rarely squamous cell carcinoma or basal cell carcinoma may arise in epidermal nevus.7

Epidermal nevus may occur as a part of epidermal nevus syndrome and may be associated with internal manifestation. These syndromes have characteristic cutaneous findings and at times relevantly specific internal findings.1  The six different types of epidermal nevus syndromes are nevus sebaceous, CHILD (congenital hemidysplasia with ichthyosiform erythroderma and limb defects) syndrome, nevus comedonicus, Becker’s nevus, Proteus syndrome, phacomatosispigmentokeratotica.

Histologically epidermis of epidermal nevus is hyperplastic. There is variable hyperkeratosis, papillomatosis and acanthosis with elongation of rete ridges. Upto 62% of biopsy specimens have these pattern and these are called non-epidermolytic epidermal nevus. About 16% of epidermal nevi show features of epidermolytic hyperkeratosis. Other histologic patterns are psoriatic type, acrokeratosisverruciformis like type and a Darier’s disease like type.1 Epidermolytic hyperkeratosis is more common in systematized type than localized type. This reaction pattern of skin was first described by Ackerman in 1970.7It occurs due to defective keratin genes (KRT-1 and KRT-2), which causes excessive and abnormal keratinization. The salient histologic features are- compact hyperkeratosis, perinuclear vacuolization of the cells in stratum malpighii, irregular cellular boundaries and increased numbers of large irregular keratohyaline granules. Epidermolytic hyperkeratosis is seen in other conditions, such as- bullous congenital icthyosiformerythroderma, icthyosisbullosa of Siemens, Vorner’spalmoplanterkeratoderma, melanocytic nevus, epidermolyticacanthoma, basal cell carcinoma and squamous cell carcinoma etc.

Main clinical differential diagnosis of epidermal nevus areepidermodysplasiaverruciformis, inflammatory linear verrucous epidermal nevus, linear psoriasis and lichenstriatus.Epidermodysplasiaverruciformis is a genetic disease characterized by HPV infection. This is usually associated with HPV 5 or 8, less commonly 3, 4, 5.1 Histologically this lesion is characterized by acanthosis, hyperkeratosis, large cells with blue-gray cytoplasm, often with dysplastic change and irregular granular layer with rare perinuclear halo. Inflammatory linear verrucous epidermal nevus (ILVEN) is a type of epidermal nevus. These lesions are also distributed in linear pattern, but they are erythematous and itchy. Histologically ILVEN is characterized by some specific features, which are absent in epidermal nevus. These are- areas of depressed orthokeratosis with underlyinghypergranulosis, alternating areas of slightly raised parakeratosis with underlying hypogranulosis.8 In linear psoriasis, the lesions may be pink to red papules or silvery scales. Typical histologic findings are regular elongation of rete ridges, thin suprapaillary plates, hypo or agranulosis, Munro microabcess and spongiform pustules of Kogoj, which are absent in epidermal nevus. In lichen striatus, the lesions are erythematous papules arranged in linear pattern following lines of Blaschko. But histologically it differs from epidermal nevus by presence of vacuolar alteration of basal layer and band like lymphocytic infiltrate.7 Treatment modalities of epidermal nevus are topical cream, cryotherapy, laser and dermabrasion. But management is difficult, because the lesions  recur unless treatment extend into dermis.


Epidermal nevus with epidermolytic hyperkeratosis is a rare condition. As this is a mosaic genetic disorder of suprabasal keratin, it can be transmitted to offspring and produce generalized epidermolytic hyperkeratosis. So genetic counseling is essential for these patients.


  1. James W, Berger T, Elston D, Neuhaus I. Andrew’s Diseases of the Skin. 12th ed. Philadelphia: ELSEVIER. 2016. pp 625-26
  2. Guite Z, Pamei D, Gunto H, Das K. Epidermolytic hyperkeratosis in verrucous epidermal nevus. Journal of medical society. 2014; 28(1): 47-8.
  3. Pollozhani N, Damevska K, Silvija D, Adjievska N, Gocev G. Epidermolytic hyperkeratosis: clue for diagnosis. Global Dermatology.  2017; 4(1): 1-3.
  4. Ngan V (2003). All about the skin. Retrieved from DermNet NZ website.  https://www.dermanet.org.nz
  5. Kouzak SS, Mendes MS, Costa IM. Cutaneous mosaicisms: concepts, patterns and classifications. An Bras Dermatol. 2013;88(4):507-517.
  6. Edler D. in Lever’s Histopathology of the Skin. 10th Philadelphia: LIPPINCOTT WILLIAMS & WILKINS; 2009. pp: 791-92
  7. Das A, Podder I, Das A, Ghosh A, Shome K. Epidermolyticblaschkoidverrucous epidermal nevus: Report of two cases. Indian J DermatopatholDiagnDermatol. 2015; 2:46-8.
  8. Meibodi NT, Nahidi Y, Jaridi Z. Epidermolytic hyperkeratosis in inflammatory linear verrucous epidermal nevus. Indian J Dermatol. 2011; 56:309-12.


Papillary Thyroid Carcinoma Arising within Mature Ovarian Teratoma: A Case Report

Papillary Thyroid Carcinoma Arising within Mature Ovarian Teratoma: A Case Report

Sadaf A, 1 Hossain MI,2  Sultana  N,3 Nasreen S,4 Rahman Z5


  1. *Dr. Anika Sadaf, MD. (Pathology) Phase B, Resident, Department of Pathology, Chittagong Medical College, Chattogram, Bangladesh, 4203. anikasadaf261189@gmail.com.
  2. Mohammad Ismail Hossain. Lecturer, Department of Pathology, Chittagong Medical College, Chattogram, Bangladesh, 4203.
  3. Nahid Sultana. Senior Consultant, Obstetrics & Gynaecology. 250 Bedded General Hospital,Chandpur, Bangladesh, 3600.
  4. Sayeeda Nasreen. Assistant Professor, Department of Pathology, Chittagong Medical College, Chattogram, Bangladesh, 4203.
  5. Zillur Rahman. Professor, Department of Pathology, Chittagong Medical College, Chattogram, Bangladesh, 4203.

 *For correspondence


Mature cystic teratoma is the commonest ovarian germ cell tumor. Though malignant transformation is uncommon, papillary thyroid carcinoma has rarely been described as associated with ovarian teratomas. We report a case of a 34-years old multiparous woman who presented with acute abdominal pain and an ovarian mass. After salphingo-oophorectomy, the patient was diagnosed as papillary thyroid carcinoma that arose within a mature cystic ovarian teratoma. To our knowledge, this is the first reported case of papillary thyroid carcinoma arising within a mature ovarian teratoma in this tertiary health care center in Chattogram. We recommend long term follow up to see any metastatic possibility.

 [Journal of Histopathology and Cytopathology, 2020 Jan; 4 (1):60-64]

Keywords: Mature cystic teratoma, papillary thyroid carcinoma, struma ovarii.


Among the ovarian germ cell tumors Mature Cystic Teratoma (MCT) is the most common and comprises 10–20% of all ovarian tumors. However, malignant transformation of MCT is not common and the incidence is 1–3%.1 Squamous Cell Carcinoma (SCC) is the commonest type, found in 80% of cases.2 Papillary thyroid carcinoma (PTC) within teratoma is one of the rarest types with ranges varying from 0.1% and 0.2%, and usually diagnosed postoperatively.3 The synchronous development of malignant struma ovarii and primary thyroid carcinoma is extremely rare, though a handful of cases were reported.4 So, presence of thyroid tissue in teratoma, should proceed with further work up to confirm the diagnosis and to explore the possibility of a malignant lesion in the mass- either primary or metastasis.5 Here we present a case of a patient with a PTC arising within a ovarian MCT.

Case Presentation
34-year-old multiparous woman who had abdominal pain, distention and irregular menstrual bleeding for approximately for 6 months, presented to the emergency service of Chittagong Medical College Hospital in May 2019 with the complaints of a sharp pain in lower abdomen, with accompanying vomitting. There was no previous medical or surgical history.

On abdominal examination, a tender mass adjacent to the left side of the umbilicus were detected. Manual examination of the vagina revealed tenderness and mass in left adnexal region. Paps smear was done with no abnormality detected. Haemogram and biochemical test results were normal except a hemoglobin level of 9.2 gm/dl. CA-125 was within normal limit and β-HCG was normal. Ultrasonography of the lower abdomen revealed a complex solid cystic mass measuring 82x62x55 mm, with mixed echotexture, compatible with dermoid cyst.

At laparotomy, a cystic mass of approximately 9x7cm size, with a white, smooth glistening surface, originating from the left ovary was observed. Opposite ovary was apparently normal and no adhesion or intra-abdominal deposit was observed. Left sided salphingo-oophorectomy was performed preserving the uterus and right ovary and sent to Department of Pathology, Chittagong Medical College, Chattogram for histopathological evaluation. On gross pathological examination, a cystic mass of 9 cm in diameter (fig-1) with 3cm fallopian tube were noted. On cross section, hair, sebum & fatty materials were come out and some thick greenish fluid was drained and some solid structure was observed on its wall (fig-2).

Microscopic examination revealed mature teratomatous component represented by skin with associated adnexal structures, muscles, fat, benign glands lined by mucin containing columnar epithelium (fig-3,4) and thyroid tissue, within the thyroid tissue foci papillary thyroid carcinoma (fig-5,6) was found. Lining cells had oval nuclei showing nuclear overlapping, grooving and intranuclear cytoplasmic inclusions. Follicles also contained amorphous eosinophilic thick colloid. The fallopian tube was unremarkable. Immunohistochemical (IHC) examination revealed positivity for TTF-1 (fig-8,9). With these findings, diagnosis of a “mature cystic teratoma with malignant transformation to papillary thyroid carcinoma” was made. Postoperatively plasma levels of T3, T4, TSH and thyroglobulin of the patient were normal. A normal parenchymal vasculature was identified by postoperative ultrasonography of the thyroid gland.


Mature cystic teratomas are also known as dermoid cysts, because they are mostly cystic, skin & skin appendages are the most common structures. Thyroid tissue is present in 10% of the all cases.6 Teratomas containing more than 50% of thyroid tissues are called struma ovarii, often presented as monodermal teratoma.7 Malignant transformation of MCT is rare; however, several types of malignancy can develop from any one of three germ-cell layers. Squamous cell carcinoma, derived from ectoderm is the commonest type; less common malignancies include soft tissue sarcomas, adenocarcinomas, malignant melanomas, basal cell carcinomas, carcinoid tumors, and thyroid carcinomas.2 Among thyroid carcinomas the most common histological type is the papillary carcinoma (44%), other types are follicular carcinoma (30%) and follicular variant of papillary carcinoma (26%).3

 The malignant change of an initially benign cystic teratoma is detected in patients between 40 and 60 years of age, older than its benign counterpart. Although the cancer occurs at any age, most patients are postmenopausal.1 The tumor may present as pelvic discomfort, with a pelvic mass on abdominal imaging (USG, CT, MRI) or during laparotomy for any other reason. Preoperative definitive diagnosis of stroma ovarii or papillary thyroid carcinoma is not possible. The only possibility of preoperative diagnosis is by radioactive iodine scan (not done routinely).8 Various case reports have been published over the past few years regarding the histological diagnoses and treatment options. The diagnoses of thyroid carcinomas arising in teratomas should be made following the guidelines for diagnosing carcinomas in thyroid gland. Disease is treatable with good out come in most cases. Only 7% and 14% of patients with papillary carcinoma and typical follicular carcinoma, respectively died of disease. Due to rarity of disease no consensus on treatment has been made, however treatment options include oophorectomy, additional thyroidectomy, radioactive iodine and long term follow up with serum thyroglobulin measurement.9

In order to determine metastatic disease, in MCT cases undergoing malignant transformation, follow up of thyroglobulin (Tg) levels is recommended. The only source of circulating Tg is the thyroid tissue and ovarian teratomas containing thyroid tissue, which is a very rare condition. However, high Tg level in benign thyroid diseases hamper determination of it as a convenient tumour marker in MCT, who did not undergo thyroidectomy and who contain thyroid tissue with malignant transformation. On the other hand, the high levels of anti-thyroglobulin antibody (anti-Tg Ab) may cause Tg levels to be erroneously low. For this reason, the follow-up of Tg levels is favourable for patients, who underwent thyroidectomy only and for patients left with no or very little thyroid tissue. In order to evaluate Tg levels correctly, follow-up of Tg levels together with anti-Tg Ab levels is advisable as persisting high levels of anti-Tg Ab indicate a persistent disease.3 In our case, Plasma T3, T4, TSH and Tg level were normal and normal parenchymal vasculature was identified by ultrasonography of the thyroid gland. Anti-Tg Ab level can’t be performed due to patient’s refusal. Logani et al., 2001 was commented the absence of normal thyroid tissue and features of teratoma, in favour of a metastatic lesion originating from thyroid gland.10 In the presented case, histologic evidence of mature teratoma, normal thyroid tissue along foci of papillary thyroid carcinoma, and positive immunohistochemical stain for thyroid transcription factor-1(TTF-1) indicates primary thyroid carcinoma arising within MCT.


Whether further therapy with total thyroidectomy and radioiodine ablation may be beneficial is unknown. The rarity of MCT cases undergoing PTC transformation impedes the establishment of a protocol for treatment and follow-up. We recommend that a long-term follow-up of these cases is needed to know more about the prognosis and to see any local recurrence or metastasis.


  1. Rim SY, Kim SM, Choi HS. Malignant transformation of ovarian mature cystic teratoma. Int J Gynecol Cancer. 2006; 16:140–44.
  2. Pineyro MM, Pereda J, Schou P, Santos DL, Peña SDI, Caserta B,Pisabarro R. Papillary thyroid microcarcinoma arising within a mature ovarian teratoma: case report and review of the literature. Clinical Medicine Insights: Endocrinology and Diabetes. 2017; 10: 1–3.
  3. Cokmez H,Gulbahar A, Yigit S, Aydin C. Oncocytic and tall columnar type papillary thyroid carcinoma arising on a mature cystic teratoma: A case report and literature review. J Pak Med Assoc. 2019; 69:116-19.
  4. Tzelepis EG, Barengolts E, Garzon S, Shulan J, Eisenberg Y. Unusual case of malignant strumaovarii and cervical thyroid cancer preceded by ovarian teratoma: case report and review of the literature. Hindawi: Case Reports in Endocrinology. 2019 Mar 17; 1-7.
  5. Yeasmin S. A case of papillary thyroid cancer and extraovarian pelvic Teratoma.Journal of the Endocrine Society. 2019; 3(1). available at:https://doi.org/10.1210/js.2019-SUN-603.
  6. Bedir R,Yılmaz R. Coexistence of papillary thyroid cancer and hashimoto’sthyroiditis developing within an ovarian mature cystic teratoma. Journal of Mid-life Health. 2019 April 10; 10: 45-47.
  7. ParulskaES, Pioch A, Chyrek EC, Wolinski K, Jurczyszyn DJ, Jedynska MJ, Majewski P, Zabel M,Ruchala M. The role of immunohistochemical examination in diagnosis of papillary thyroid cancer in strumaovarii. Folia Histochemica Et Cytobiologica. 2019;57(1):35–42.
  8. Naeem M, Iqbal M, Imran MB,Tabassum R. Malignant strumaovarii: a rare case report. European Journal of Medical Case Reports. 2017; 2(1): 30-32.
  9. Haider A, Hussain M, Hassan U, Loya A. Papillary thyroid carcinoma arising in ovarian teratomas: A report of three cases. Journal of Islamabad Medical & Dental College (JIMDC). 2015 Sep 27; 4(2): 88-90.
  10. Logani S, Baloch ZW, Snyder PJ, Weinstein R, LiVolsi VA. Cystic ovarian metastasis from papillary thyroid carcinoma: A case report. Mary Ann Liebert, Inc. 2001; 11(11): 1073-1075.


Histopathological Diagnosis of Rhinofacial Entomophthoramycosis in a 16-Year-Old Girl: A Case Report

Histopathological Diagnosis of Rhinofacial Entomophthoramycosis in a 16-Year-Old Girl: A Case Report

*Asaduzzaman,1 Khandkar T,2 Rahman DA3 


  1. *Dr. Asaduzzaman, Assistant Professor of Histopathology, Sheikh HasinaNational Institute of Burn and Plastic Surgery, Dhaka, Bangladesh. dr.asad37@gmail.com
  2. Tahmina Khandkar, Assistant Registrar, Paediatric Nephrology, National Institute of Kidney Diseases and Urology, Shere-E-Bangla Nagar, Dhaka
  3. DM Arifur Rahman, Assistant Professor, Department of Pathology, TMSS Medical College, Bogura

 *For correspondence


Rhinoentomophthoramycosis is an uncommon and severely disfiguring disease. It mainly involves the mucosa of the nares, nasal passages, nasal sinuses, nasopharynx, mouth and spreads to adjacent tissues causing disfigurement of face. Histopathological examinations and mycological cultures are the gold standard for confirmation of entomophthoramycosis. We report a case of a 16-year-old girl who presented with swelling and ulcer of face. Clinical presentation along with typical histopathologic findings were diagnostic in this case.

 [Journal of Histopathology and Cytopathology, 2020 Jan; 4 (1):55-59]

 Keywords: Entomophthoramycosis, zygomycosis, fungal infection of face, fungal granuloma, splendore-Hoeppli reaction


Rhinoentomophthoramycosis is not so common in Bangladesh as well as other parts of the world. It is a grossly disfiguring disease. The medically important class zygomycetes are in two orders, the Mucorales and the Entomophthorales. Rhinofacialentomophthoralesmainly affects the mucosa of the nares, nasal passages, nasal sinuses, nasopharynx, mouth, and spreads to adjacent tissues causing disfigurement of the face. It occurs predominantly in immunocompetent individuals and live as saprophytes in soil and decaying plant matter.1 Rhinofacialconidiobolomycosis affects the subcutaneous tissues of the face, especially the paranasal sinuses as well as the deeper organs.2 We report the case of a teen-aged female who presented to us with facial swelling and ulcer and was diagnosed by histopathology.

 Case Report

An immunocompetent16-year-old girl from Chittagong presented to the outpatient department of Sheikh Hasina National Institute of Burn and Plastic Surgery with a one year history of progressive nasal and maxillofacial swelling. Swelling of face started from the nasal bridge and gradually spread into the left side of the face. For the facial swelling she had received multiple treatments, including glucocorticoids and antibiotics. But for the last one month she developed multiple ulcers with purulent discharge over the swelling. The physical examination reveals an ulcer over upper part of left cheek and swelling over bridge of nose. Adjacent area revealed erythema, edema, and tenderness over the nasal dorsum and forehead, extending to the soft tissue around left eyes (Fig. 1). Initially she has undergone biochemical and radiological investigations.

Laboratory investigations included a haemoglobin of 11.6 gm/dl, total leucocyte count 12.36×109/L with a differential count within normal range, and platelet count was 400.1x 109/L. Other biochemical tests were within normal limit. Serology for hepatitis B surface antigen and human immunodeficiency virus 1 and 2 were negative. MRI of face revealed diffuse soft tissue thickening involving the paranasal sinuses, skin and subcutaneous tissue in left side of face extending into the left zygomatoco-temporal region.  Direct naso-endoscopic examination revels left sided middle meatus. Septum and lateral wall of nose were congested. Middle meatus was adherent to the lateral wall of nose. At right side, crest of nose, middle meatus was distorted, nasal septum was absent/dehiscent on posterior part. There was no growth on nasopharynx. Biopsy specimens were obtained from multiple sites, including the forehead and the nose. The gross specimen consisted of two skin covered piece of tissue; largest one measured 4x3x1.5 cm and smaller one measures 1.5×0.8×0.5 cm. Skin surface showed multiple ulcers. The cut surface was solid and tan gray. Histopathological examination showed a chronic granulomatous inflammation (Fig. 2) with broad nonseptate branching hyphae surrounding amorphous eosinophilic substance, the Splendore-Hoeppli reaction (Fig. 3). Marked lympho-plasmacytic cell infiltrate with tissue eosinophilia and foreign body type of giant cells containing fungal elements were present. Periodic acid Schiff and Gomori-Methenamine-Silverstain highlighted the fungal elements and the surrounding amorphous eosinophilic material (Fig. 4 and 5). She was diagnosed as a case of Rhinofacialentomophthoramycosis. The patient was then on systemic antifungal therapy.


Rhinofacialentomophthoramycosis is an uncommon fungal infection; it mostly occurs in the tropical and subtropical regions of different parts of the world. G. Bras reported the first case of a Jamaican native in 1965. It is predominantly a chronic mucocutaneous and subcutaneous infection. The name Entomophthorales was coined from the Greek word “Entomon” meaning insect implicating their pathogenic nature in insects. Formerly, the two orders, namely Mucorales and Entomophthorales, were classified in the phylum Zygomycota. Hibbett et al. suggested a comprehensive phylogenetic classification of the kingdom Fungi, and the phylum Zygomycota was eliminated as a result of polyphyletic characteristics.3 Therefore, the taxa belonging to Zygomycota were distributed among the phylum Glomeromycota and four subphyla of uncertain placement (incertaesedis). Entomophthorales and Mucorales as well as two other orders (Kickxellales and Zoopagales) were raised to the rank of subphyla and renamed as EntomophthoromycotinaMucoromycotinaKickxellomycotina,and Zoopagomycotina.4 Entomophthoromycotina encompasses twogenera that cause human infection, Basidiolus and Conidiolus.

Humans suffering from rhinoentomophthoromycosis get infected by the attachment of conidia of Ccoronatus to nasal/sinusoidal mucosa. Initially, the disease presents like sinusitis.5 A nodule at the nostrils indicates expansion into the subcutaneous fat.6 The infection spreads within the subcutaneous fatty layers of the nasal bridge, eyelids, cheek, and upper lip. Swellings are firm, indolent, and, initially, often reddened and warm, while later they are often itchy.7 Mucosal swellings rarely affect laryngeal structures or cause dyspnoea. Ulcerations of skin or mucosa may occurs, as we found in our case. Skin-adherent structures, eye motility, and vision usually remain unaffected; and bones, vessels, muscle, and lymph nodes are rarely involved. The course of the disease is usually benign.8

The diagnosis is based on a combination of mycologic and histopathological tests, and clinical presentation.Histological examinations and mycological cultures are the gold standard for confirmation of entomophthoromycosis. Biopsy of skin lesions is preferred for diagnosis than pus, as the chances of positive identification with potassium hydroxide preparation and culture are better with tissue specimens.9 Entomophthoromycosis can be easily differentiated from other fungi by their characteristic hyphal morphology. The hyphae are broad, aseptate, or sparsely septate, with right-angle branching.10 The histological inflammatory reaction shows infiltration with lymphocytes, plasma cells, epithelioid cells, multinucleate giant cells, and histiocytes with an area of central necrosis that is surrounded by eosinophilic infiltration. This phenomenon is called Splendore–Hoeppli phenomenon.10 Our patient had all these typical features. PAS stain and GomoriMethenamine-Silver (GMS) stains are useful to demonstrate the fungal hyphae. Examination under fluorescent microscopy using fluorescent dye (Blankophor) wet mount preparation increases the sensitivity of diagnosis.11 Definitive diagnosis requires culture, polymerase chain reaction testing, and immunohistochemistry.

Treatment for endomophthoromycosis ismedical and surgical. Systemic antifungal therapy and or surgical debridement is the primary choice in most cases. Several antifungal agents are used for the treatment of endomophthoromycosis such as itraconazole and amphotericin B.12


The entomophthoromycosis is a severe fungal disease that can affect both immunocompetent and immunocompromised individuals. Despite the clinical features, the disease requires biopsy for diagnosis, as histological examinations and mycological cultures are the gold standard for confirmation of entomophthoramycosis.This disease have a favorable prognosis if early treatments can be ensured.


  1. Manning RJ, Waters SD, Callaghan AA. Saprotrophy of Conidiobolus and Basidiobolus in leaf litter. Mycol Res. 2007; 111: 1437–1449.
  2. Prabhu RM, Patel R. Mucormycosis and entomophthoramycosis: A review of the clinical manifestations, diagnosis and treatment. ClinMicrobiol Infect 2004;10 Suppl 1:31-47.
  3. Hibbett DS, Binder M, Bischoff JF, Blackwell M, Cannon PF, Eriksson OE, et al. A higher-level phylogenetic classification of the fungi. Mycol Res 2007;111:509-47.
  4. Kwon-Chung KJ. Taxonomy of fungi causing mucormycosis and entomophthoramycosis (zygomycosis) and nomenclature of the disease: Molecular mycologic perspectives. Clin Infect Dis 2012;54Suppl 1:S8-15.
  5. Choon SE, Kang J, Neafie RC, Ragsdale B, Klassen-Fischer M, Carlson JA. Conidiobolomycosis in a young Malaysian woman showing chronic localized fibrosingleukocytoclasticvasculitis: a case report and meta-analysis focusing on clinicopathologic and therapeutic correlations with outcome. Am J Dermatopathol. 2012; 34: 511–522.
  6. Choon SE, Kang J, Neafie RC, Ragsdale B, Klassen-Fischer M, Carlson JA. Conidiobolomycosis in a young Malaysian woman showing chronic localized fibrosingleukocytoclasticvasculitis: a case report and meta-analysis focusing on clinicopathologic and therapeutic correlations with outcome. Am J Dermatopathol. 2012; 34: 511–522.
  7. Martinson FD. Chronic Phycomycosis of the Upper Respiratory Tract: RhinophycomycosisEntomophthorae. Am J Trop Med Hyg. 1971; 20: 449–455.
  8. Ribes JA, Vanover-Sams CL, Baker DJ. Zygomycetes in Human Disease. ClinMicrobiol Infect. 2000; 13: 236–301.
  9. Chowdhary A, Randhawa HS, Khan ZU, Ahmad S, Khanna G, Gupta R, et al.Rhinoentomophthoromycosis due to Conidioboluscoronatus. A case report and an overview of the disease in India. Med Mycol 2010;48:870-9.
  10. El-Shabrawi MH, Arnaout H, Madkour L, Kamal NM. Entomophthoromycosis: A challenging emerging disease. Mycoses 2014;57Suppl 3:132-7.
  11. Kumar Verma R, Shivaprakash MR, Shanker A, Panda NK. Subcutaneous zygomycosis of the cervicotemporal region: Due to Basidiobolusranarum. Med Mycol Case Rep 2012;1:59-62.
  12. Prabhu RM, Patel R. Mucormycosis and entomophthoramycosis: A review of the clinical manifestations, diagnosis and treatment. ClinMicrobiol Infect 2004;10Suppl 1:31-47.



C3 Glomerulopathy: Overview on a New Disease Entity

C3 Glomerulopathy: Overview on a New Disease Entity


*Rahman DA,1 Banu SG2


  1. *Dr. DM Arifur Rahman, Assistant Professor, Pathology, TMSS Medical College, Bogura. arifurrahmandm@gmail.com
  2. Sultana Gulshana Banu, Associate Professor, Pathology, Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka.

 *For correspondence


The diagnosis of membranoproliferative glomerulonephritis (MPGN) has recently undergone change from an electron microscopy-based classification scheme to one based largely on immunofluorescence findings. Recent advances in our understanding of the disease pathology of membranoproliferative glomerulonephritis has resulted in its re-classification as complement C3 mediated glomerulopathy (C3G) and immune complex-mediated glomerulonephritis (IC-GN). The new concept is based on its underlying pathogenesis, with a key pathogenetic role for the complement alternative pathway (AP), rather than on histomorphological characteristics. This overview summarizes the current state of knowledge about the C3 glomerulopathy.

 [Journal of Histopathology and Cytopathology, 2020 Jan; 4 (1):48-54]

 Keywords: C3 glomerulopathy, Dense deposit disease, C3 glomerulonephritis, Membranoproliferative glomerulonephritis


C3 glomerulopathy (C3G) is an emerging kidney disease caused by dysregulation of the alternative complement pathway.1,2,3 The characteristic pathology of this disease is glomerular depositions of dominant C3 with absent or weak immunoglobulins. Therefore, C3G is basically diagnosed by immunofluorescence (IF) and it can reveal various patterns of glomerular injuries by light microscopy(LM).4,5 Following the recent trend of pathogenesis-based reclassification of glomerular diseases, glomerulonephritis associated with alternative complement dysregulation is collectively referred to as C3G.6 Because laboratory detection of alternative complement dysregulation is still uncommon in current practice, predominant C3 deposition by IF is an initial finding that suggests C3G. However, glomerular diseases caused by mechanisms other than alternative complement dysregulation may occasionally satisfy “C3-dominant deposition with scanty immunoglobulins” as stated in the current consensus report.4 Clearly, pathogenesis based classification in glomerular diseases is an important prospect for appropriate therapies, but the entity of C3G still presents dilemmas in diagnostic practice by lack of clear definition and pathogenic basis. We review the current status of C3 glomerulopathy, histological, immunofluorescence findings and treatment

MPGN and C3 Glomerulopathy

Understanding the limitations of current MPGN classification requires a brief review of complement activation pathways. There are two main pathways of complement activation: the classic pathway, which is activated when IgG or IgM antibodies bind to antigens; and the alternative pathway, which does not require the presence of antibodies and can be auto activated by spontaneous cleavage of C3 to C3b, leading to the formation of C3 convertase. The electron microscopy-based classification can result in overlap between types I and III. Both types have been considered to be immune complex-mediated glomerulonephritis but, observations suggest that some cases of MPGN type I or MPGN type III are mediated by complement, not immune complexes.7,8,9

So, the historical classification required modification. It is not based on pathogenesis and there is significant overlapping, which is described earlier. In recent years, there have been great advances in our understanding of the pathogenesis of MPGN, particularly in the area of complement-mediated C3 glomerulopathies, including DDD and C3 glomerulonephritis. 4,10

It is proposed that MPGN be classified into two major groups: immunoglobulin (Ig)-mediated and complement-mediated (C3G). If immunoglobulins are present on IF studies, the evaluation should include a work-up for infections, autoimmune diseases, and monoclonal gammopathies, including cryoglobulins. It should be kept in mind that Ig-mediated MPGN also is associated with extensive C3 (and C4) deposition along the capillary walls via activation of the classic pathway of complement. On the other hand, if the IF studies show predominantly C3 and are negative or show no significant staining for Igs, an in-depth study of the AP is warranted. Ig-mediated MPGN is more likely to be present in adults whereas complement-mediated MPGN is more likely to be present in children and young adults. It is likely that C3G noted in children and young adults is due to genetic mutations in complement-regulating proteins, whereas it is acquired in adults as a result of development of autoantibodies to complement-regulating proteins. Initial evaluation of AP should include serum MAC levels, an alternative pathway functional assay, and hemolytic complement assays. If the initial screening is positive, it should be followed by genetic analysis for mutations and enzyme-linked immunosorbent assays for the presence of autoantibodies to complement-regulating proteins.11-14

The current approach, therefore, distinguishes those forms of MPGN with isolated C3 deposits (including DDD and C3GN) as alternative complement pathway-mediated C3G from those cases of MPGN that are mediated by the classical complement pathway with deposits of Ig and complement.

Clinical Presentation

Membranoproliferative glomerulonephritis or C3G are rare diseases with an estimated incidence of 1–2 per million per total population.15  Patients with C3G present with a variety of symptoms, ranging from a mild disease with asymptomatic microhaematuria and/or proteinuria to a severe disease with nephritic or nephrotic syndrome and renal impairment. Renal survival was worse if the GFR at diagnosis is <60 ml/min/1.73 m2.16

The kidney is the major target, possibly due to the morphological specificities of the glomerular capillaries, in particular the fenestrated endothelium, with exposure of the glomerular basement membrane to serum (complement). Although low levels of C3 are considered a hallmark feature of C3G, in one study low C3 levels were only detected in about 50 % of the patients. Therefore, a normal C3 level does not rule out C3G.17

Nasr et al., 2009 studied 32 paediatric and adult patient of dense deposit disease and Lu., et al 2012 studied 92 children and adult patient of dense deposit disease. Both of the studies reveal at presentation, almost all patients have proteinuria usually with haematuria. Nephrotic-range proteinuria is present in two thirds of the patients. Full nephrotic syndrome in 12% to 65% in different series conducted by Lu et al., 2006 and Servais et al., 2012. Persistently, low serum levels of C3 are found in most patients (approximately 80%). Servais et al have reported the clinical features in 56 patients with C3 glomerulopathy without dense deposits (C3GN) and compared them with 29 patients with DDD and 49 patients with immune complex MPGN type 1. The mean age at diagnosis for C3GN was 30, which was significantly higher than for DDD; 25% of patients were below16 years of age. Twenty-seven percent of patients with C3GN had nephrotic syndrome at presentation as compared with 38% of patients with DDD and 65% of patients with MPGN type I.18,19,20

 Light Microscopy

Light microscopic findings in C3 glomerulopathy can range from membranoproliferative lesions to mesangioproliferative or endocapillary proliferative lesions with or without presence of crescents. In rare instances, light microscopy might be normal. The electron dense osmophilic deposits as seen characteristically in DDD are found within the glomerular basement membrane, and as rounded deposits in the mesangium. In many cases, deposits are also seen in Bowman’s capsule and tubular basement membranes. C3 glomerulopathy, in which deposits do not completely fulfill criteria for dense deposits, are classified as C3GN. Electron microscopy in C3GN shows a complex pattern of mesangial increase and glomerular basement membrane thickening. Differing combinations of subendothelial, intramembranous, and subepithelial deposits are noted.21,22,23

DDD is defined by the presence of dense osmiophilic transformation of the GBM on EM, and on light microscopy, the morphology is variable. While it is clear that a membranoproliferative pattern of glomerular injury with increased lobulation, mesangial expansion, and capillary wall thickening with segmental double contours is common, a range of other patterns of glomerular involvement also occur. Walker et al., 2007 collected 69 cases of DDD from centers in North America, Europe, and Japan. They identified four distinct histologic patterns on light microscopy: membranoproliferative (25%), mesangial proliferative (45%), crescentic (18%), and acute proliferative and exudative (12%).21 In the Columbia series conducted by Nasr et al., 2009 which includes 32 cases of DDD, the frequencies were MPGN (44%), mesangial proliferative(28%), endocapillary proliferative (19%), and crescentic GN (9%). These reports emphasize that fewer than 50% of cases of DDD have MPGN morphology. Morphologically, most C3GN cases show either a mesangial proliferative or membranoproliferative pattern.18

The dense deposits are recognized on light microscopy by thickening of the GBMs by ribbon-like glassy intramembranous deposits. They stain strongly with eosin and appear somewhat refractile (hyaline). They are intensely periodic acid-Schiff (PAS) positive, and the trichrome stain shows them to be fuchsinophilic (red) although this reactivity varies among specimens.23

 Immunofluorescence findings

Immunofluorescence shows characteristic C3 fragment deposition in C3GN.16  But the deposition of C3 is not always isolated. According to the current consensus report, the term ‘‘isolated’’ was replaced by “dominant staining of C3 defined as at least two orders of C3 intensity greater than that of any other immune reactant.” 4

Nasr et al., 2009, Walker et al., 2007, West and McAdams, 1998 studied the immunofluorescence findings. The invariable finding in DDD and C3GN is the presence of C3 in the glomeruli. Intense staining for C3 is noted along the glomerular capillary walls and often in the glomerular mesangial regions. The C3 deposition is usually diffuse and global. The GBM staining may be continuous or discontinuous. The early components of complement, C1q and C4, are usually absent, although occasionally C1q is found.  Immunoglobulins are usually absent or show only focal and segmental staining. If they are present, they often stain much less intensely than C3 and they are usually of the IgM type with a segmental distribution; IgG and especially IgA are less common.18,21,24

Treatment and Prognosis

Modality of treatment of MPGN is difficult and its prognosis is also guarded. About 50% develop chronic renal failure within 10 years. There is a high incidence of recurrence in transplant recipients, particularly in dense-deposit disease. Treatments with steroids, immunosuppressive agents, and antiplatelet drugs have not been proved to be materially effective.25

 Eculizumab, the first available anticomplement therapy, blocks at the level of C5 and has revolutionized the treatment of complement-mediated diseases as well as C3 glomerulopathy.13 This agent is a humanized monoclonal antibody that binds with great affinity to C5 proteins, inhibiting cleaving into C5a and C5b and blocking production of the C5b-9 membrane attack complex. Reports of individual cases showed improvement after treatment, with reduced serum creatinine and proteinuria. Bomback et al 2012, reported that, after 1 year of therapy with eculizumab, there was reduction in active glomerular proliferation and neutrophil infiltration three of five patients, consistent with effective C5 blockade.26


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  22. Joh K, Aizawa S, Matsuyama N, Yamaguchi Y, Kitajima T, Sakai O, Mochizuki H, Usui N, Hamaguchi KI, Mitarai T. Morphologic variations of dense deposit disease: Light and electron microscopic, immunohistochemical and clinical findings in 10 patients. Pathology International. 1993; 43(10):552-65.
  23. Habib R, Gubler MC, Loirat C, Maiz HB, Levy M. Dense deposit disease: a variant of membranoproliferative glomerulonephritis. Kidney international. 1975; 7(4):204-15.
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  27. Röth A, Dührsen U. Treatment of paroxysmal nocturnal hemoglobinuria in the era of eculizumab. European journal of haematology. 2011; 87(6):473-9.

Comparison between Bethesda System and Conventional System for Standardization of Reporting Thyroid Cytopathology

Comparison between Bethesda System and Conventional System for Standardization of Reporting Thyroid Cytopathology

 *Saleheen S,1 Rahman DA,2 Chowdury MA,3 Haque MM,4 Habib S,5 Khan KH6


  1. * Saied Saleheen, Assistant Professor, Department of Pathology, Sheikh Hasina Medical College, Tangail. saleheen44@gmail.com
  2. DM. Arifur Rahman, Assistant Professor, Department of Pathology, TMSS Medical College, Gokul, Bogura,
  3. Mehdi Ashik Chowdury, Assistant Professor, Department of Pathology, Jahurul Islam Medical College, Bajitpur, Kishoreganj.
  4. Mohammad Mahbubul Hoque, Lecturer, Department of Pathology, Sheikh Sayera Khatun Medical College, Gopalganj.
  5. Saequa Habib, Associate Professor, Department of Pathology, Bangabandhu Sheikh Mujib Medical University, Dhaka.
  6. Kamrul Hasan Khan, Professor, Department of Pathology, Bangabandhu Sheikh Mujib Medical University, Dhaka.

 *For correspondence


Background: Fine-needle aspiration cytology (FNAC) is considered as an effective test to screen and diagnose patients with thyroid swelling for surgical management. But FNAC still suffers because of its inherent limitations as well as variability in its diagnostic terminology.The Bethesda System of Reporting Thyroid Cytopathology (TBSRTC) may improve the state. This study was to report the experience in using this reporting system to redistribute the cytological diagnoses made by conventional system and also to evaluate the specificity, sensitivity, accuracy and predictive values as a tool to compare both the methods based on the correlation between cytopathology and histopathology.

Methods: A total of 73 patients presenting with thyroid swelling were subjected to FNAC and reporting was done according to the conventional system and TBSRTC. The cytological diagnosis was correlated with the histopathological diagnosis. The sensitivity, specificity, predictive values were calculated considering cytology as screening test.

Results: In this study, TBSRTC was found superior because of higher sensitivity (91.66%) and specificity (97.77%) as compared to conventional system (80.76% and 87.23% respectively). Positive predictive value, negative predictive value and diagnostic accuracy of Bethesda system were 95.65%, 95.65% and 90.41% respectively which were also significantly higher as compared to those of conventional system (77.78%, 89.13% and 84.93% respectively).

Conclusions: TBSRTC may improve the efficacy of thyroid FNAC as a screening test.

 [Journal of Histopathology and Cytopathology, 2020 Jan; 4 (1):38-47]

 Keywords: Comparison, Thyroid FNAC, Bethesda system (TBSRTC), Conventional system, Histopathology, Standardization


Fine Needle Aspiration Cytology (FNAC) is a quick, cost-effective and minimally invasive outpatient procedure used worldwide in the initial diagnosis of thyroid swellings. As it can distinguish between benign and malignant lesions quite effectively, it is the preoperative screening method of choice worldwide.1 Before the routine use of thyroid Fine Needle Aspiration (FNA), the percentage of surgically resected thyroid nodules that were malignant was 14%.2 With current thyroid FNA practice, the percentage of resected nodules that are malignant surpasses 50%.3

However, due to the lack of a standardized system of reporting, pathologists have been using different terminologies and diagnostic criteria, leading to confusion amongst clinicians in the interpretation of the cytopathology report and ultimately hindering a definitive clinical management.4 It has also hindered the sharing of clinically meaningful data among multiple institutions.5 To mitigate this confusion all the pathologists need to use the same diagnostic criteria and terminology.6

Various reporting formats of thyroid FNAs have been suggested in the literature since the 1970s when thyroid FNAs began to be the subject of publications, and new formats continued to emerge.7 Several classification schemes have been suggested by various authors based on personal/institutional experiences but there is general support for the utilization of a tiered classification system.5 With this background, the National Cancer Institute (NCI), Bethesda, Maryland, United States, published an atlas and guidelines using standardized nomenclature for the interpretation of thyroid FNAC known as The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC).4 It categorized the thyroid FNAC diagnoses into six groups with well-defined cancer risk and clear indications for further clinical management.8 It has also increased the interobserver reproducibility of cytopathological diagnoses of thyroid lesions.9-12

TBSRTC has been well received by both pathologists and clinicians and has been widely implemented by pathology laboratories in USA and in several European countries.13 Following publication of TBSRTC, the reporting system used in the United Kingdom since 2002, was updated by a working group of The Royal College of Pathologists and is now quite similar to TBSRTC.14 But TBSRTC still has to go a long way in getting acceptability in many countries of Asia and Africa.10

A good number of studies have been carried on in several countries in Asia (India, Pakistan, Iran, Korea and KSA) regarding usefulness of TBSRTC and it has been proved useful for management of patients with thyroid swelling in these countries.9,11,15-20 But this relatively recent six category scheme still needs to be validated by more prospective studies with histopathological correlation.16

In Bangladesh, there is no known reporting scheme using tiered classification system. The utility of thyroid cytopathology reporting according to TBSRTC in context of Bangladesh is also unexplored. Standardization of the reporting system by TBSRTC may result in improvement of the quality, homogenization and also reduce interobserver variability of thyroid cytopathology reports. In this context, this study was performed to assess the predictive values, sensitivity and specificity and accuracy of the TBSRTC in comparison with that of the conventional system used in the BSMMU, Dhaka, Bangladesh with histopathological correlation. The view was to observe the usefulness of Bethesda system for standardization of thyroid cytopathology reporting in the context of this country (Bangladesh).


This is a cross sectional study carried out at the Department of Pathology, Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka during the period from March 2015 to February 2017. A total of 73 patients presenting with thyroid swelling were included in this study, who has undergone FNA followed by the biopsy of the thyroid lesions. Patients presenting with thyroid swelling in any lobe of thyroid detected by clinical palpation (multinodular, solitary nodule, diffuse goiter etc) were included except those unwilling to be involved into the study.

All clinical information were recorded in a pre-designed proforma including demographic features, address and telephone contacts (for histological follow up). Results of all the routine investigations with special attention to ultrasonography of neck, serum T3, T4, and TSH levels and thyroid scintigraphy were noted where available.     

FNA of all patients was performed at the Department of Pathology, BSMMU.  Smears were stained with Papaniculaou (PAP) and Hematoxylin and Eosin (H&E) stains. Cytological findings were recorded and diagnoses were made according to both conventional and TBSRTC for each cases. For the TBSRTC reporting the Atlas10was used as manual (Table I). Reports were issued according to conventional method.

Koss’ Diagnostic Cytology and its histopathologic bases21 was followed conventionally as reference book in this department. The diagnoses made by conventional system are mostly based on its reference. The diagnoses were: Non-neoplastic lesions: Nodular goiters (NG) including cystic degeneration (CD), Lymphocytic thyroiditis (LT), Hashimoto thyroiditis (HT), Nodular goiter with co-existent thyroiditis, Multinodular goiter (MNG).

 Cellular follicular lesion (CFL): Cellular smears on cytology that included goiters with adenomatous changes, follicular adenomas and carcinomas, as well as the follicular variant of papillary carcinomas. In BSMMU suspicious cytology, atypia of undetermined significance and other gray zone cytology are also included within this diagnosis.

 Neoplastic lesions: Papillary thyroid carcinoma (PTC), suggestive of papillary carcinoma, medullary thyroid carcinoma (MTC) etc.

Biopsy specimens or histopathological reports of the patients undergoing surgery following the FNA interpretation under this study were collected. The histopathological findings were correlated with cytopathological findings and were recorded accordingly.

Descriptive analytical statistics was calculated. Thyroid FNA was considered as a ‘screening test’ and histopathology as gold standard. FNA benign was considered to be negative and the remaining categories were considered to be positive because they indicated significant risk of malignancy and led to a recommendation of surgery.8 Sensitivity, specificity, accuracy, the positive predictive value (PPV) and negative predictive value (NPV) were calculated from the available data by statistical formulae. In this study, Thyroid FNA has been considered as a screening method as TBSRTC is formed by NCI as a screening method to triage the patients effectively into groups that need surgery and the other that do not.5

For calculating statistical parameters nondiagnostic (ND) and AUS/FLUS cases were excluded as non-definitive diagnoses and categories, SFM and malignant were put together in most of the studies.15,16,22-24 In this study, the inadequate/ND cases were reaspirated and have been included rationally in other categories. Those which were still inadequate, had been excluded from statistical analysis.


Out of the 73 cases 62(84.9%) were female and 11(15%) were male. The age of the patients ranged from 16 to 70 years with average age around 40 years.

According to the conventional system forty five (61.64%) cases were diagnosed nodular goiter. Five (11.11%) of these lesions were found to be neoplastic (one benign and 4 malignant) on histopathology. Although all PTC and suggestive of PTC categories were found neoplastic and also malignant, 60% of the cellular follicular lesions (9 out of 15) were neoplastic (one benign and 8 malignant) and the rest were benign on final histological diagnosis.

The lesions when redistributed according to the Bethesda system: 46 (63%), 04 (5.4%), 03 (4.1%), 08 (10.95%), 12(16.4%) of the lesions were diagnosed as Cat-II, Cat-III, Cat-IV, Cat-V and Cat-VI respectively. The redistribution of the lesions after application of Bethesda system is shown in Table-II.

Out of 73 cases, 64 (22 neoplastic and 42 non-neoplastic) cytological diagnoses were concordant on both the conventional and Bethesda systems. One lesion was non-neoplastic on conventional but diagnosed neoplastic on Bethesda system while 04 neoplastic lesions by conventional system were categorized as non-neoplastic by Bethesda system. Three non-neoplastic and one neoplastic case according to conventional system were categorized as Cat- III (AUS) by Bethesda system. The CFL on conventional system were distributed by the Bethesda system into various categories that matched well (Table-III) with final histological diagnoses.

All the neoplastic lesions irrespective of benign and malignant neoplasm were considered positive for both the histological and cytological diagnoses, as they recommend for surgical excision. The concordances of the cytological diagnoses made by two methods with the final histological diagnoses are shown in Table IV.

Granulomatous thyroiditis: GT, Follicular adenoma: FA, Follicular carcinoma: FC, FVPTC: Follicular Variant of PTC, WDTUMP: Well differentiated tumor of uncertain malignant potential.

Diagnoses made according to TBSRTC shows increased overall concordance with hisotoathological diagnosis than that of the conventional system.

FNA interpretation by conventional method yielded significant false positive (6) and false negative (5) diagnoses. While analyzing the smears by the Bethesda system had decreased both the false positive (1) and false negative (2) interpretations. The sensitivity, specificity, accuracy and predictive values calculated for both the methods by using the statistical formulas are compared to each other in the Table V.

Sensitivity and positive predictive value (PPV) of the Bethesda system were found better (91.66% and 95.65% respectively) when compared to that the conventional system (80.76% and 77.78% respectively). The specificity and negative predictive values (NPV) were also found higher for Bethesda system (97.77% and 95.65%) in comparison to that of the conventional system (87.23% and 89.13% respectively). Diagnoses according to the Bethesda categories were 90.41% accurate where accuracy for the conventional system was 84.93%.


Reporting according to the conventional system included 41 (about 56.16%) patients into benign category, while category-II (Benign) in the Bethesda system included 44 (60.27%) patients. All (12) the suspicious for malignancy and malignant diagnoses on conventional system corresponded to category V and VI of Bethesda system. It reflects that there was actually no significant change in diagnosis of unequivocally benign and malignant cases according to the two systems of reporting.

15 (20.54%) CFL diagnosed by conventional system was the major field where the Bethesda system varied markedly. So, CFL was a “gray zone” diagnosis that included some benign (26.67%) and malignant (53.33%) cases.25 These cases when reclassified by the Bethesda system yielded more specific results with good histological correlation (Table IV). This difference can be explained by- i) Subjective underscoring of some neoplastic cytologies which are of SFM category in more objective Bethesda system and  ii) Assigning the follicular lesion diagnosis for some hyper cellular smears of goiter arranged in folded sheet appearance.

The 06 false-positive FNA diagnoses in conventional system included cellular smears of histologically nodular goiters that were interpreted as CFLs. Four of these cases were interpreted benign (category-II) by Bethesda system and 01 case was designated category-IV (suspicious for Hurthle cell neoplasm) because of relative abundance of Hurthle cells showing pleomorphism. Five cases were false negative for conventional method, 04 of which were due to compromised cytology samples. The rest one case diagnosed conventionally as nodular goiter that was histologically follicular adenoma and Category-IV (SFM) in Bethesda system.

When compared with other studies using TBSRTC with histological follow up, sensitivity and NPV of the present study were consistent with most of the studies (Table VI). The specificity and PPV were higher than most of the other studies, which may be due to small sample size in this present study.


By dint of its higher sensitivity, specificity, predictive values and accuracy TBSRTC has been proved to be better than  conventional system for reporting thyroid cytopathology. So, it should be useful for standardization of thyroid cytopathology reporting. However, studies needed to explore its effect in reducing inter-observer variation of reporting thyroid cytopathology as well as its usefulness to the clinicians in decision making.


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  2. Hamberger B, Gharib H, Melton LJ, Goellner JR, Zinsmeister AR. Fine-needle aspiration biopsy of thyroid nodules: impact on thyroid practice and cost of care. The American journal of medicine. 1982 Sep 1;73(3):381-4.
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Histopathological Spectrum of Prostatic Lesions Evaluated in a Tertiary Hospital

Histopathological Spectrum of Prostatic Lesions Evaluated in a Tertiary Hospital

 *Sultana SS,1 Hossain S,2 Rahman A3


  1. *Dr. Sk Salowa Sultana, Assistant Professor, Department of Pathology, Ad-Din Women’s Medical College. salowasultana257@gmail.com
  2. Shahadat Hossain, Associate Professor, Department of Pathology, Ad-Din Women’s Medical College.
  3. Afiqur Rahman, Professor of Urology, Department of Urology, Ad-Din Women’s Medical College.

*For correspondence


Objective: To determine the age distribution of various prostatic lesions, to evaluate histopathological  pattern  of prostatic lesions  and  to analyze adenocarcinoma  of prostate according to Gleason  system.

Methods: This was a retrospective study comprising of 178 cases, carried out at the department of Pathology, Ad-din Women´s  Medical College Hospital during the  period of January 2017 to December 2019.

Results: Out of 178 cases, 159(89.32%) were diagnosed as benign lesion, nodular hyperplasia being the commonest one. Prostatic adenocarcinoma was found in 16(9%) cases, majority of which belonged to Gleasons score 7.

Conclusion: Histopathological examination of prostatic biopsy specimen is essential for diagnosis of benign and malignant lesions, to rule out the incidental carcinoma and HGPIN.

 [Journal of Histopathology and Cytopathology, 2020 Jan; 4 (1):33-37]

 Keywords: Nodular hyperplasia of prostate, prostatic carcinoma, HGPIN


The  prostate that weights up to 20 gm in normal adult depends for its subsequent growth and differentiation on androgenic hormones.1,2  Lesions of prostate are extremely common over the age of 50 years and important cause of morbidity and mortality in male in advance age. Pathological processes affecting this organ include inflammation, benign nodular enlargement and tumor.1 The clinical incidence of the diseases is only 8% during the 4th decade  but it reaches 50% in the 5th decade and 75% in the 8th decade.2 Benign prostatic  hyperplasia(BPH) and carcinoma are increasingly frequent with advancing age.3  BPH results from hyperplasia of both stromal and epithelial cells, gradually being enlarged, compress and narrow the urethral canal and often leads to urinary obstruction. Inflammation of prostate is known as prostatitis and divided into acute, chronic and granulomatous prostatitis. Prostatic carcinoma is one of the most common malignancies affecting men, also it is the sixth leading cause of cancer death in male.4 Among the prostatic malignancies 95% is adenocarcinoma. premalignant lesion of prostatic adenocarcinoma  is known as high grade intraepithelial neoplasia (HGPIN). The objective of this study was to determine the age distribution of various prostatic lesions, to evaluate histopathological  pattern  of prostatic lesions  and  to analyze adenocarcinoma  of prostate according to Gleason  system.


The study was conducted in the Department  of Pathology, Ad-din Women´s Medical College Hospital – a  tertiary level hospital of Dhaka, Bangladesh. The study period was from January 2017 to December 2019. The data were collected retrospectively from histopathology register. A  total of 178 TURP (Transurethral resection of prostate) were evaluated. The received specimen were fixed in 10% formalin and routine paraffin processing followed by hematoxylin and eosin staining was done and the slides were examined under light microscope. The specimens were ananlyzed as type of specimen, age of the patient, histopathological  pattern and final diagnosis. The tumour were classified according to 2016 WHO classification and histological grading was done using modified Gleason´s system. Data  were analyzed using tables, figures and percentage.


A total of 178 cases were included in our study, all of which (100%) were TURP specimen.  In the present study, most of the prostatic lesions were benign(89.32%) followed by malignant (9.6%) and HPIN (1.12%) and ratio of benign and malignant lesions is 1:9, approximately.

In the present study, benign lesions were mostly found (45%) in the age group of 61-70 years  and 34% in the age group of 51-60 years,  whereas malignant lesions were common  41% in the age group of 71-80 years and 29% in the age group of 61-70 years of age. In our study, benign lesions(159) were nodular hyperplasia of prostate 130(73.03%) and nodular hyperplasia of prostate with co-existing prostatitis 29(16.3%). Out of 29 cases of prostatitis, 24 cases were chronic non specific prostatitis, 2 cases were granulomatous prostatitis and 3 cases were acute prostatitis.  In our study, 2(1.12%) cases were diagnosed as HGPIN and 17(9.6%) cases were diagnosed as malignant. Most of the malignant cases 16(9%)  were prostatic adenocarcinoma and 1(0.56%) was metastatic adenocarcinoma. In this study, 41% cases of malignant belong to 71-80 years age group and 29% cases belong to 61-70 years age group. According to Gleason score, most commonly (81.25%) found grade was grade 7, in this study.


We enrolled a total of 178 cases in our study, all of which (100%) were TURP specimen. Bhatta S et al5 have found 88.54% specimen of TURP in their study. Screening procedure like trans-rectal ultrasound, prostate specific antigen (PSA) are still used, but biopsy remains the gold standard for final diagnosis.6 In the present study, most of the prostatic lesions were benign (89.32%) followed by malignant (9.6%) and HPIN (1.12%). These findings are similar to the studies done by Bhatta S et al,5 Bal et al,7 Jehoram  et al,8 and Bhat S et al.9 They found (89.58%), (87%), (93%) and (92.4%) cases of BPH in their study, respectively. In our study, ratio of benign and malignant lesions is 1:9, approximately.

In the present study, benign lesions were mostly found 45% in the age group of 61-70  years  and 34% in the age group of 51-60 years,  whereas malignant lesions were common  41% in the age group of 71-80 years and 29% in the age group of 61-70 years of age. These findings are in concordance with other studies.10,11,12

In our study, benign lesions(159) were nodular hyperplasia of prostate 130(73.03%) and nodular hyperplasia of prostate with co-existing prostatitis 29(16.3%). Out of 29 cases of prostatitis, 24 cases were chronic non specific prostatitis, 2 cases were granulomatous prostatitis and 3 cases were acute prostatitis.  Bhatta S et al found 24(25%) cases of prostatitis associated with nodular hyperplasia of prostate, out of which 22 cases were chronic non specific prostatis and two cases were acuteprostatis.5 Prostatic carcinoma is one of the most common malignancies affecting men. In our study, 2(1.12%) cases were diagnosed as HGPIN and 17(9.6%) cases were diagnosed as malignant. Most of the malignant cases 16(9%)  were prostatic adenocarcinoma and 1(0.56%) was metastatic adenocarcinoma. Bhatta S et. al5found 2.08% of HGPIN and 8.34% of prostatic carcinoma. Also Deshmukh BD et. al11 and Bhat S et. al9 found similar observation. In this study, 41% cases of malignant  belong to 71-80 years age group and 29% cases belong to 61-70 years age group. Bhat S et. al12  found 75% cases of malignancy diagnosed after 60 years. All the cases of prostatic adenocarcinoma were graded according to Gleason score which determine the tumour aggressiveness.In this study, most commonly 13(81.25%) found grade was grade 7. Albasri et al.13 found Gleasons score 5-7 as the commonest among 71 cases of prostatic adenocarcinoma. Bhat S et. al9 found 56.16% of adenocarcinoma with Gleason score 8-9.


Histopathological  examination of prostatic lesions is essential for diagnosis and management. Prostatic lesions are common in the age group of 60-70 years. All the specimen received were TURP. Benign prostatic hyperplasia (BPH) was predominant type among all the lesions. Majority of the malignant lesions were incidental diagnosis and most of the malignant lesions were prostatic adenocarcinoma. Emphasis should be  given to identify premalignant lesions.


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