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jhc-2019-jul-v-3-n-2-coexistence-hossain-mi

Case Report

Coexistence of Primary Tuberculosis and Metastatic Ductal Carcinoma in Axillary Lymphnode: Report of a Rare Case

* Hossain MI,1 Sadaf A,2 Sultana N,3 Khan AS4

 

  1. * Mohammad Ismail Hossain. Lecturer, Department of Pathology, Chattogram Medical College, Chattogram, Bangladesh.ismail. tushar@gmail.com
  2. Anika Sadaf, MD (Pathology) Phase B Student. Department of Pathology, Chattogram Medical College, Chattogram, Bangladesh.
  3. Nahid Sultana, Senior Consultant, Obstetrics & Gynaecology, Chandpur 250 bed General Hospital, Chandpur, Bangladesh.
  4. Professor Dr. AKM Shahabuddin Khan, Ex Professor, Department of Pathology, Cumilla Medical College, Cumilla, Bangladesh. Chief Consultant, Cytosite (Histopathology Laboratory), Chandanpura, Chattogram.

 *For correspondence

 Abstract

Concomitant breast cancer metastasis and tubercular lymphadenitis in axillary lymph node is an extremely rare occurrence. Co-existence of two pathologies in one organ always poses a diagnostic and therapeutic challenge. Here, we report a case of 47-years old female presented with lump in the right breast. Fine-needle aspiration cytology (FNAC) from breast and axillary lymph node revealed ductal carcinoma with axillary metastasis. The patient underwent total mastectomy with axillary lymph node dissection and microscopy showed concomitant presence of metastatic tumor and tubercular lymphadenitis in axillary nodes. Majority of previously reported cases were breast cancer with axillary lymphadenopathy having tubercular foci, while our patient had a metastatic carcinoma and tubercular granulomatous foci in the same lymph node with the absence of tubercular foci elsewhere. The case is being reported for its rarity. It also indicates that FNAC can fail to detect mixed lesions unless multiple punctures from many sites are performed.

 [Journal of Histopathology and Cytopathology, 2019 Jul; 3 (2):162-166]

 Key Words: Ductal carcinoma, Tuberculosis, Metastasis, Axillary lymph node, Coexistence

 Introduction

The synchronous occurrence of tuberculosis and carcinoma is unusual. Coexistence of tuberculosis and metastatic carcinoma in axillary lymph nodes, without pulmonary or mammary tuberculosis is even rarer.1 It is always adiagnostic and therapeutic challenge that simultaneous presence of two diseases in one organ. Though carcinoma of the breast and tuberculosis (TB) both are common in developing countries, their coexistence is uncommon.2 Warthinfirst described two cases of coexistence of TB and carcinoma of mammary glands in axillary node in 1899.3 Kaplan et al. examined the frequency of the coexistence between different cancer types and TB in a retrospective study and reported that the prevalence of TB was 19 per 10,000 cases of breast cancers.4 Here we report a rare case of metastatic duct cell carcinoma of breast in axillary lymph nodes harboring tubercular lymphadenitis that was incidentally discovered during the histological examination, wherein no evidence of tuberculosis was found elsewhere.

 Case Report

A 46-years old multiparous woman presented at out-patient department of Chattogram Medical College Hospital with the history of painlesslump in her right breast for about last one and halfmonths. On examination, a fixed and hard nodule measuring 3 cm in diameter was palpable in the lower outer quadrant of right breast.The overlying skin, areola and nipple were apparently normal. Multiple right axillary nodes, ranging from 0.5 to 2 cm in diameter were also palpable with mild tenderness. No palpable lump was detected in contralateral breast & axillaand no cervicalor inguinal lymphadenopathy. There was no past history/family history of tuberculosis, malignancy or any other chronicmedical illness.She was taking combined oral pills for contraception for about 20 years.

The ultrasonographyrevealed a nodule of 46x39x32 mm in the lower outer quadrant of the right breast, associated with a group of axillary lymph nodes the largest one measuring 22×15 mm.

Routine hematological & biochemical tests were within normal limit except a hemoglobin level of 9.2 g/dl with raised ESR and chest X-ray showed unremarkable change. Fine needleaspiration cytology (FNAC) from right breast lump revealed highly cellular smears showing atypical ductal cells in clusters and dispersed singly. The cells had moderately pleomorphic nuclei, coarsely granular chromatin and 1–2 prominent nucleoli. FNAC from the largest axillary node revealed tumor metastasis. A diagnosis of ductal carcinoma with axillary metastasis was given on cytology. A right modified radical mastectomy performedandthe specimens were sent to Cytosite (A private cyto-histopathological laboratory) for histopathological diagnosis. Specimen showed a firm to hard, whitish about 40×35 mm nodular lump in the breast. On axillary dissection, eight lymph nodes were isolated larger one measured 20 mm in diameter. Cut surface ofmost of the nodes were adherent and gray-white in colour (Figure 1).

The histological examination revealed a tumor composed of neoplastic ductal cells arranged in cords, nests and tubules invading into the stroma. These cells had moderate amount of cytoplasm with moderate nuclear pleomorphism and 1-2 prominent nucleoli. Mitotic count was less than ten/10 high power fields. Surgical resection margins were free of tumor, where the base was tumor-free. Lymphovascular tumor emboli were also evident with no perineural involvement.

Out of eight nodes three showed tumor metastases and two of the lymph nodes showed epithelioid cell granulomas with Langhans type giant cells and central caseaous necrosis (Figure 3, 4, 5).

Immunohistochemical (IHC) examination revealed overexpression of estrogen & progesterone receptor and negativity for Her-2/neu in the breast lesion. With these findings, diagnosis of “invasive ductal carcinoma, grade II (Nottingham modification of Bloom Richardson grade) with concomitant regional nodal metastasis done and caseating granuloma” found, so “AJCC staging II”was made. Since preoperatively tuberculosis was not suspected and no other clinical feature of TB was found, mantoux test, culture, serology or polymerase chain reaction were not performed. Due to unavailability modified Ziehl–Nielsen staining on axillary tissue and CD68 immunostain for epithelioidhistiocytes not done.

 Discussion

TB remains a major public health problem worldwide. According to the Global Tuberculosis Report 2018, it affected 10 million people in 2017 and is responsible for 1.2–1.4 million deaths globally in HIV-negative patients. It is caused by Mycobacterium tuberculosis and most often affects the lungs. About 23% of the world’s population (1.7 billion people) has latent tuberculosis, with a risk of reactivation of 5–15%.5 Tubercular lymphadenitis is the most common form of extra pulmonary tuberculosis. But isolated axillary tubercular lymphadenitis without any evidence of clinical disease in any other organ is extremely uncommon in adults. Axillary tubercular lymphadenitis can be accounted for by either retrograde spread from the mediastinal nodes or hematogenous spread from a subclinical focus.

An alternative explanation for the co-occurrence of TB and metastasis could be activation of a silent Mycobacterium tuberculosis infection due to immunocompromised state in cancer patients.6 Tubercle bacillus can exist in a state of microbial latency within the macrophage of the granulomas for the lifetime. Factors that disturb host immunity can allow the tubercle bacillus to cause endogenous reinfection.7

In general, TB is diagnosed by clinical history, erythrocyte sedimentation rate, chest X-ray, Ziehl–Nielsen staining, polymerase chain reaction (PCR)based detection of acid fast bacilli (AFB) and others. But a significant proportion of cases of extra-pulmonary TB may be negative for chest X-rays or regular stains for AFB.8

The clinical features of breast carcinoma may reveal nodules and ulcerations,appearance of lymphadenopathies lead us to suspect a metastatic tumor. It is the histological examination that enabled making the differential diagnosis.9 Ina few cases diagnosis have been made through preoperative investigations like cytology or core biopsy. PET-CT as we know is the imaging of choice in certain cancers like lung cancer, its role in breast cancer is limited.8

Breast cancer patientsalso may suffer reactivation of TB during their treatment. It not only disturb the treatment protocol but also the clinical and radiologic findings confuse the follow up process since a malignant and a tubercular lesion may be indistinguishable.7 Axillary lymph node metastasis is the most important factor in the staging of ductal carcinoma and the number of metastatic axillary nodes alter the stage. As tuberculosis also produces nodal enlargement, this can mimic or complicate the staging of malignant disease.6 Therefore, pathologists and lab technicians should also be aware and vigilant in ruling out possible differentials such as metastasis, tuberculosis, fat necrosis, actinomycosis, suture granuloma accordingly.10

 Conclusion

Simultaneous presence of axillary tubercular lymphadenitis and metastatic carcinoma is a significant but rare event that can confuse and complicate the diagnosis, grading, staging and most importantly, the treatment of the disease. It is important for the physician in endemic countries like ours to consider the possibility of a granulomatous disease masquerading as axillary metastasis in order to correctly address both diseases.

 

 References

  1. Pandey M, Abraham EK, Chandramohan K and Rajan B. Tuberculosis and metastatic carcinoma coexistence in axillary lymph node: A case report. World Journal of Surgical Oncology; 2003;1(3):1-3.
  2. Tulasia NR, Rajub PC, Damodaranb V and Radhikab TS. A spectrum of co-existent tuberculosis and carcinoma in the breast and axillary lymph nodes: Report of five cases.The Breast; 2006;15:437–439.
  3. Caroppo D, Russo D, Merollam F, Ilardi G, Caro MD, Lorenzo PD, Varricchio S, Mascolo M and Staibano S. A rare case of coexistence of metastasis from head and neck squamous cell carcinoma and tuberculosis within a neck lymph node. Diagnostic Pathology; 2015;10(197):1-3.
  4. Kaplan MH, Armstrong D, Rosen P. Tuberculosis complicating neoplastic disease:A review of 201 Cases. Cancer 1974;;33:850-858
  5. Almeida S, Valentim M, Neto C, Cerol M, Boticário M, Santos MI, Gameiro A. Extrapulmonary Tuberculosis Presenting as a Suspected Case of Metastatic Breast Cancer. European Journal of Case Reports in Internal Medicine 2019. DOI:10.12890/2019_001062
  6. Pujani M, Khan S, Hassan MJ, Jetley S and Raina PK. Coexistence of metastatic breast carcinoma and primary tuberculosis in axillary lymph nodes: A report of a rare case; Breast Disease. 2015;35:195–198.
  7. Baslaim MM, Al-Ghamdi MA, Al-Numani TS, Ashour AS and Al-Amoudi SA. Tuberculosis in 7 breast cancer cases: Diagnostic and therapeutic challenges. J Mycobac Dis; 2013;3(3):1-4.
  8. Mukhopadhyay T, Nandi M, Bhattacharya S, and Khan EM. Contralateral contiguous tuberculous lymphadenitis in a case of right breast carcinoma – Diagnostic dilemma. J Can Res Ther.2015;11:102-6.
  9. Ouedraogo AS, Bambara HA, Ademayali FAH, Ramde WN, Sawadogo RJ, Savadogo I, Ouattara S, Barry1 H, Lamien AS, Lompo OM. Anatomo-clinical case: coexistence of tuberculosis with axillary lymph node metastasis in breast carcinoma. Open Journal of Pathology; 2018;8:132-138.
  10. Lee CH. and Sharif SJ. Primary breast tuberculosis (TB) in a patient with known invasive breast carcinoma: A case report. Med J Malaysia.2016;71(3):149-151.
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jhc-2019-v-3-n-2-Is-histopathological-kabir-an

Review Article

Is Histopathological  Examination Essential  for the Diagnosis of Psoriasiform Dermatitis?

*Kabir AN,1 Rahman MM 2

  1. *Dr. AKM Nurul Kabir, Associate Professor, Department of Pathology, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh. kabir56@gmail.com
  2. Mohammad Mosiur Rahman,  Assistant Professor, Department of Pathology, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh

 *For correspondence

Abstract

Psoriasiform dermatitis encompasses a wide range of diseases, some of which show both clinical and histological overlap. Psoriasis is generally thought to be a genetic disease that is triggered by environmental factors. Psoriasis is characterized by an abnormally excessive and rapid growth of the epidermal layer of the skin.  Abnormal production and an over abundance of skin cells result from the sequence of pathological events in psoriasis, can be shown as a higher Ki-67 index compared with normal appearing, non-lesional skin. Morphometric analysis  of  histological features can also give a quantitative dimension  to histopathology  in diagnosis of psoriasis and in differentiating from other psoriasiform dermatitis. Psoriasis is also regarded as a T-cell mediated disorder, mainly CD4+ (helper/inducer) lymphocytes along with CD8+ subsets are known to occur.  The patient often prove to be a diagnostic dilemma for both dermatologists and pathologists alike. However, clinical features when considered alone may not be reliable, as they vary with both disease duration and treatment.  Though to give a precise diagnosis one relies on clinical correlation, histopathology is essential as it is possible to assign specific diagnosis in most cases with a logical and systematic histopathological approach. Morphometry along with the help of Ki-67 & Cyclin D1 and other immunostains of keratinocytes, and immunophenotyping of T-cell infiltrate, a definitive diagnosis can be made.

 [Journal of Histopathology and Cytopathology, 2019 Jul; 3 (2):151-161]

Key words: Psoriasis, Psoriasiform dermatitis, Morphometry, Ki-67, CD4+, CD8+

 Introduction

Psoriasiform  dermatitis  encompasses a wide range of inflammatory dermatoses, some of which show both clinical and histological overlap.  The term psoriasiform means  that  the lesion either clinically or histopathologically mimic  psoriasis and this group includes: psoriasis- the prototype of psoriasiform dermatitis,1 and others as  seborrheic dermatitis,  pityriasis rubra pilaris (PRP), allergic dermatitis, atopic dermatitis , nummular dermatitis,  lichen simplex chronicus (LSC), prurigo nodularis,  pityriasis rosea (PR), inflammatory linear verrucous  epidermal nevus (ILVEN) and mycosis fungoides (MF). Besides, clinical features in one patient may differ at different times and the diagnosis get obscured.3 As there is varied clinical presentation, a definitive histopathological  diagnosis is essential in the treatment of such inflammatory dermatoses.1 It is a challenging  task even to experienced pathologists to give a precise diagnosis every time and one relies also on clinical correlation. However, a stepwise systematic histopathological approach enables one to reach at a specific diagnosis in most cases.2

The morphometry parameters such as length of rete ridges, the length of dermal papillae and the ratio of length/average width of rete redges are statistically significant in the differentiating  psoriasis from psoriasiform dermatitis and can be used in addition to routine histopathology.3 As the prototype of psoriasiform dermatitis, psoriasis is a hyperproliferative skin disorder with increased epidermal turnover rate and mitotic index, proliferation markers Ki-67 & Cyclin D1 immunostain of keratinocytes can be added as diagnostic tools  to differentiate from other non- psoriasiform dermatitis.4  Expression levels of pRb and p53 were found to be higher in the psoriasis group in a study,  compared with the normal epidermis.5  Psoriasis is an autoimmune skin disease and regarded to be T- cell mediated disorder. CD4+ T-cells are important in initiating and maintaining the pathogenic process of psoriasis but cross-primed CD8+ T-cells are the main effector cells. Mixtures of CD4+ T cells and CD8+ T-cells are found in papillary dermis and epidermis of psoriatic lesion.  Psoriasiform lesions on the other hand show a high proportion of CD4+ T-cells in dermis.  Immunophenotyping of T-cell infiltrate in the lesion can be done in differentiating the cases.6

 

History of Psoriasis

History of psoriasis begins in Ancient Greece, when psoriasis, leprosy, and other inflammatory skin disorders were believed to be the same condition and the Greeks termed the skin diseases as  psora, lepra and lichen. Psora referred to itch, and lepra from lopos & lepo (the epidermis & to scale respectively). Hippocrates (460-377 BC) used the word lopoi to describe the dry, scaly, disfiguring disorders.  The Old Testament also lumped together many cutaneous   disorders, including leprosy and psoriasis, by the biblical term tsaraat or zaraath. Lepers were considered divinely punished, and cruelty was imposed upon those who were suffered from psoriasis and leprosy alike. Roman medical writer Celsus (25BC-45AD) first described papulosquamous diseases, suggesting as psoriasis one of these. Galen (133-200) first used the term psoriasis, but his description was likely represented seborrheic dermatitis. Gilbert (1797-1866) and Hebra finally distinguished the clinical picture of psoriasis from that of leprosy.7

 Epidemiology

Although psoriasis occurs worldwide, it is a common chronic inflammatory skin disorders affecting 1.5-2% population in the western countries and 1.3% in general population.6 The prevalence of psoriasis is low in certain ethnic groups such as the Japanese.8

Psoriasis can present at any age and has been reported at birth and in older people of advanced age. A bimodal age of onset has been recognized in several large studies. The mean age of onset for the first presentation of psoriasis can range from 15 to 20 years of age, with a second peak occurring at 55–60 years. Henseler and Christophers studied a series of 2147 patients and also reported as two clinical presentations of psoriasis, type I and II. Type 1 begins on or before age 40 years; Type II begins after the age of 40 years. Type I disease accounts for more than 75% of cases. Patients with early onset, tended to have more relatives affected and more severe disease than patients who have type II psoriasis. In addition, strong associations have been reported with human leukocyte antigen (HLA)-Cw6 in patients with early onset of psoriasis. The course and progress of psoriasis is unpredictable. In one study, 39% of patients reported complete remission of disease at the age between one and 54 years. Higher figures have been reported in Japan.8 A family history of the disease is common. Approximately 30% of patients have a first-degree relative with psoriasis, and the risk of psoriasis increases with the number of affected relatives a patient has.9

 Lifestyle and Morbidity

There is a link between cigarette smoking and psoriasis severity. There is sufficient evidence that aggravation of psoriasis is associated with alcohol consumption. Various recent studies report association of diabetes and other cardiovascular diseases to the severe form of psoriasis.10 Recent research suggests that patients with psoriasis have a systemic inflamma­tory state, putting them at increased risk of cardiovascular complications, including metabolic syndrome, peripheral vascular disease, stroke, myocardial infarction, and cardiac death.11  Psoriasis is increasingly being recognized as a disease that not only affects the skin but also has multi-systemic implications. Increasing epidemiological evidence suggests that patients with psoriasis may be more obese compared with the general population. Although the exact mechanism underlying the epidemiological association between psoriasis and obesity is uncertain, researchers have theorized that adipocyte elaboration of pro-inflammatory cytokines may exacerbate psoriasis.12 Many, but not all, studies have shown a positive association between metabolic syndrome and cardiovascular disease (CVD) and psoriasis, especially for (young) patients with moderate to severe disease. A recent study showed that Glyc A, which is a novel biomarker for systemic inflammation  was associated with psoriasis.13  Nearly 60% of psoriasis patients and 40% of psoriatic arthritis patients report their disease as a large problem in their everyday life. Psychosocial limitations of both diseases include enduring low self-esteem, feeling physically unattractive or sexually undesirable and avoiding social activities.14

Etiology

Etiology of psoriasis remains unknown,  even though, it is believed to be multifactorial with numerous key components including genetic susceptibility, environmental triggers in combination with skin barrier disruption and immune dysfunction.15 Various data suggest that infection is an important trigger for psoriasis. Streptococcal throat infection can initiate and exacerbate chronic psoriasis.15 Another research has shown that the composition of the cutaneous microbiota is related to many dermatological diseases including  psoriasis, atopic dermatitis, and acne vulgaris.16

Genetic Factors

Epidemiological studies have demonstrated that psoriasis has an important genetic component, where the role of environmental triggers (e.g., stress, mechanical trauma and streptococcal infections) is well documented.  Familial recurrence is also documented and disease concordance is higher in monozygotic than dizygotic twins. So, psoriasis is widely regarded as a multifactorial disorder caused by the interaction between inherited susceptibility alleles and environmental risk factors.17 The molecular genetic basis of psoriasis is complex, however, there are evidence that multiple genes are involved. Seven major psoriasis susceptibility loci have been reported and   a major susceptibility locus for psoriasis is at 6p21, referred to as PSORS1 and is overrepresented in all populations tested.  An association between psoriasis and other loci has also been reported on chromosomes 1p (PSORS7), 1q (PSORS4), 3q (PSORS5), 4q (PSORS3), 17q (PSORS2), and 19p (PSORS6). The strength of associations between such genes and susceptibility to psoriasis, apart from PSORS1, is variable, may relate, in part, to heterogeneity among different populations.8

 Mechanism

Psoriasis is characterized by an abnormally excessive and rapid growth of the epidermal layer of the skin. Abnormal production of skin cells and an overabundance of skin cells result from the sequence of pathological events in psoriasis.  Skin cells are replaced every 7 days in psoriasis rather than the usual about 53 days.18 Exclusive cellular “responsibility” for the induc­tion and maintenance of psoriatic plaques has not been clearly defined. Increased proliferation of keratinocytes and endothelial cells in conjunction with APC/T cell/monocyte/macrophage inflammation leads to the distinct epidermal and vascular hyperplasia that is characteristic of lesional psoriatic skin.15  CD8+ T cells seem to be dominant in the epidermis whereas the CD4 + T cells predominant subset in the dermis.  Activated CD4+ T cells produce a variety of  cytokines  including interleukin-2 (IL-2), TNFα and γINF.  TNFα stimulating keratinocytes may produce  IL -8, a potent T- lymphocyte and neutrophil chemoattractant  and may involved in the formation of Munro microabscess. γINF is believed to play in important role in the initiation of psoriatic lesion.18 In individuals with a genetic predisposition, external stimuli such as trauma (known as Koebner phenomenon), infections, stress, drugs, and alcohol can all trigger an initial episode of psoriasis. This initial trigger activates the innate immune system (Figure 1). Complexes of the antimicrobial peptide LL-37 and host DNA/RNA, both released by keratinocytes after common epidermal damage, activate plasmacytoid dendritic cells (pDCs) to produce large amounts of type I IFNs (α/β).  Subsequently, type I IFNs trigger maturation and differentiation of dermal dendritic cells (dDCs), and these dDCs then stimulate autoreactive T cells. Thereby, psoriatic autoimmune T cells are biased to produce Th1 and Th17/Th22 cells and which induce TNFα,/INFγ and IL-17/IL-22 production respectively. These mediators act on keratinocytes, leading to the activation and proliferation. In addition, type I IFNs directly upregulate IL-22 receptor (IL-22R) on keratinocytes, increasing their responsiveness to IL-22, and inhibits terminal differentiation and induces hyperproliferation of keratinocytes leading to epidermal hyperplasia, resulting psoriasis.19  In psoriasis , along with epidermal changes there is markedly increased dermal vascularity. The dermal vascular changes have been evaluated and shown to be due to change from arterial-type vessels to venules. The vascular changes may also precede the epidermal alterations, as shown in some studies.20

Clinical Features

Psoriasis is a papulosquamous disease with variable morphology, distribution, severity and course. Papulosquamous diseases are characterized by scaling papules and plaques.8  There are five clinical subtypes of psoriasis: vulgaris (plaque), guttate, pustular, inverse, and erythrodermic. The most common variant of psoriasis is plaque psoriasis, which includes approximately 85%–90% of psoriatic patients.15 The lesions are typically distributed symmetrically on the extensor surfaces of elbows, knees, and lumbosacral area and scalp. Psoriasis may also develop at the site of trauma, known as Koebner’s phenomenon.  Guttate psoriasis has drop-shaped lesions.  Inverse psoriasis forms red patches in skin folds. Pustular psoriasis presents as small non-infectious pus-filled blisters. Erythrodermic psoriasis involves widespread inflammation and exfoliation of the skin over most of the body surface. Psoriatic nail disease affects fingernails more commonly than toenails with small pits in the nail plate.8

Clinical Diagnosis

Psoriasis is a clinical diagnosis, and a skin biopsy is usually not necessary for a classic presentation of the disease.9 Diagnosis of psoriasis is usually based on the appearance of the skin. The characteristic lesions are sharply demarcated, scaly, erythematous plaques, papules, or patches on skin that may be pruritic and/or painful. They may be ovoid, round or irregular and often distributed symmetrically.9 Auspitz sign, named after Heinrich Auspitz, where there is pinpoint bleeding on removal of scales from the lesions of psoriasis. The test by which Auspitz sign is elicited by light tangential scratching with the edge of glass slide is called as Grattage test can be used  as clinical tool.21

Microscopic Diagnosis

Histopathology is considered as a “gold standard” for the diagnosis of most dermatological conditions including psoriasis.21 Common histological features in  psoriasis vulgaris are  hyperkeratosis, parakeratosis,  psoriasiform hyperplasia (Figure 2),  Munro microabscess / spongioform pustule of Kogoj,   thin suprapapillary plate, hypogranulosis, dilated capillaries in papillary dermis and dermal inflammation.1  However, other than  Munro microabscess, spongioform pustule of Kogoj and dilated tortuous capillaries in papillary dermis,  the remaining features , such as  parakeratosis,  psoriasiform hyperplasia can be seen  also in chronic eczematous dermatitis, such as atopic dermatitis, nummular dermatitis or allergic contact dermatitis and appear to be “psoriasiform”.18  However, following a systematic approach one can reach at conclusive diagnosis.

 

Tirumalae described a detail  microscopic description for definitive diagnosis as follows.2

 Scanning magnification

Examination of microscopic sections under scanning magnification forms the first step. The presence of evenly elongated, thin rete ridges with equally long dermal papillae can seen in one condition i.e., psoriasis. All other diseases exhibit an uneven psoriasiform pattern, where rete ridges are of uneven of lengths and thickness with thick supra-papillary plates as in PRP (Figure 3).

 Stratum corneum

The normal basket-weave pattern is lost in most cases and it is common to find parakeratosis. Parakeratosis can be present in small mounds or may be broad and confluent.  Mounds of parakeratosis can be present throughout the epidermis in conditions like psoriasis and dermatophytosis, in seborrheic dermatitis confined to the infundibular ostia or seen in both locations in PRP.  The classic “checkerboard” pattern i.e., parakeratosis staggered in both vertical and horizontal fronts is seen in PRP. Confluent parakeratosis is seen in dermatophytosis, syphilis, pityriasis lichenoides chronica (PLC) and most importantly, in MF. A sharply defined thick zone of parakeratosis alternating with orthokeratosis and mild papillomatosis are features of ILVEN.

Epidermis

Diminished or absent granular layer is seen in classic psoriasis, but is not a constant feature. Significant amounts of plasma in the scale crust goes against a diagnosis of psoriasis, and  large amounts of plasma and a rapidly proliferating epidermis are hostile to fungi. The finding of spongiotic vesicles in a psoriasiform dermatitis are seen in allergic contact/nummular dermatitis and seborrheic dermatitis. Spongiotic psoriasiform pattern is also encountered in patch-stage of MF.

 Changes in Papillary Dermis

Psoriasis is characterized by thin supra-papillary plates and elongated dermal papillae with dilated, tortuous capillaries. The presence of extravasated erythrocytes is a sign of acuteness and is seen in eruptive psoriasis and PR. Vertical streaks of collagen with uneven psoriasiform acanthosis and compact orthokeratosis is diagnostic of LSC. However, changes of LSC can be superimposed on any chronic, itchy dermatitis including psoriasis. In contrast, thin haphazard, wiry bundles of collagen are seen in the papillary dermis in PLC and MF.

 Nature of Infiltrate

Most of the psoriasiform dermatoses are dominated by lymphocytes in the dermis. When eosinophils are present among them, it indicates allergic/contact dermatitis or a drug eruption.  However, eosinophils are not a pre-requisite for diagnosis of either of these conditions. Histiocytes and plasma cells in a psoriasiform dermatitis with scale crusts give hints for secondary syphilis. Superficial and deep infiltrates are seen in syphilis and lichen striatus (LS).  In LS, there is a psoriasiform lichenoid pattern with deep infiltrates of lymphocytes along the adnexae, especially around the eccrine glands.

 Morphometry

Morphometric analysis of histological features can give a quantitative dimension to histopathology. The results of morphometry parameters such as length of rete pegs, the length of dermal papillae and the ratio of length/average width of rete pegs  can help in achieving the accurate diagnoses of psoriasis and psoriasiform dermatitis. In one study using eye-piece micrometer with the light microscope without special software and found statistically significant results in differentiating psoriasis from psoriasiform dermatitis. The mean length of rete pegs was 1.74 times greater in psoriasis when compared to psoriasiform dermatitis. The ratio of average length and width of rete pegs was considered representative of shape of rete pegs. The higher ratio of length over average width of rete pegs confirms the histopathological finding of slender long rete pegs, which favors the diagnosis of psoriasis.

The dermal vascular changes have been evaluated in different studies by electron microscopy and shown to be due to change from arterial-type vessels to venules. The vascular changes may also precede the epidermal alterations, as shown in some studies. Morphometric parameters of papillary dermal vessels in psoriasis and to compare these with psoriasiform lesions can also be used. Morphometric evaluation of dermal vasculature in psoriasis has shown increased endothelial and luminal volume of vessels compared to control subjects. On light microscopic evaluation of CD34 immunostained sections, biopsies from psoriasis showed much greater microvascular staining in the papillary dermis in comparison to psoriasiform dermatitis.20

 Role of Immunohistochemistry

  Ki-67 and Cyclin D1 Immunostaining

As Psoriasis is a hyperproliferative skin disorder with increased epidermal turnover rate and mitotic index,  proliferation markers Ki-67 (Figure 4) and Cyclin D1 immunostaining  can be used to differentiate psoriasis from non-psoraisis psoriasiform dermatitis( NPPD ) (Figure 5). In a study Ki-67 and Cyclin D1 positive cells were counted per mm2 of suprabasal and total epidermal area by Sezer. et al. 4

Psoriatic lesions have been shown to reveal a higher Ki-67 index compared with normal appearing, non-lesional skin.  In psoriasis group, suprabasal Ki-67 positive cells were more than 75% of the total epidermal Ki-67 positive cells in the epidermis (including basal and suprabasal cell population) in psoriasis group, whereas this ratio was lower than 75% (cut-off value) in NPPD group. The suprabasal/total epidermal count ratio for Cyclin D1 immunostaining was higher in the psoriasis group compared with the NPPD group, but a cut-off value to distinguish between these two was not detected, suggesting that Ki-67 is a more sensitive marker than Cyclin D1 in terms of the presence of a cut-off value and could be a useful tool for dermatopathologists to differentiate psoriasis from other psoriasiform dermatitis.4

 pRb and p53 Immunostaining

Expression levels of pRb and p53 were found to be higher in the psoriasis group  in a study,  compared with the normal epidermis.  The phosphorylation of pRb is associated with cyclin D1, cyclin E and P16.  pRb phosphorylation in psoriasis is incresed by the activity of cyclin D1 and Cyclin E and showed a higher expression of pRb than that of normal epidermal expressions.  Total basal layer cell counts for p53 expression were found to be significantly higher in psorisis group compared with the normal group.5 It is postulated that increased expression of p53 in psoriatic skin is a physiological reaction indicating the attempt  to counteract the proliferation and to repair DNA errors, and is most often expressed as an increased number of mitoses.22

 CD4+ and CD8+ cell distribution

Psoriasis also known as a skin disorder with immunological factors playing an important role in its pathogenesis, and lymphocytic infiltrates, mainly CD4+ and CD8+ cells provide a major contribution in the initiation and maintenance of the lesion. Psoriasis is an autoimmune skin disease characterized by T-cell mediated hyperproliferation of keratinocytes. It is regarded as a T-cell mediated disorder, mainly CD4+ (helper/inducer) lymphocytes along with CD8+ (suppressor/cytotoxic) subsets are known to be associated. T-lymphocytes in psoriatic lesion are in an activated state with expression of HLA-DR and IL-2 receptor. Mixtures of CD4+ T-cells and CD 8+ T-cells are present in papillary dermis and epidermis of psoriatic lesion. T-cell also plays a role in the pathogenesis of psoriasiform lesions, and reported a high proportion of CD4+ T-cells in the dermis on immunohistochemical analysis.6

A comparative study was done by Rana. et al to see the infiltration of CD4+ and CD8+  cells in psoriasis and psoriasiform lesions. The inflammation in the epidermis was present in about half of psoriasis cases and predominant cells were polymorphs. In the upper dermis, inflammation was evident in all cases with predominant cells were lymphocytes. Inflammation in the lower (reticular) dermis was present with mostly lymphocytes.

In psoriasiform lesions the inflammation was present in the epidermis in only few cases showing mixtures of polymorphs and lymphocytes. Within the upper dermis, all cases showed inflammation with predominant of lymphocytes. Few cases showed inflammation in the lower dermis with lymphocytes as majority of the cells. Immunohistochemical staining was done to see the distribution of CD4+ and CD8+ cells.  the distribution of CD4 positive cells was seen in psoriasis patients.  In the epidermis of psoriasis cases only one fifth were positive for CD4+ cells. In the upper dermis, CD4+ cells were present in 92% cases.  In the lower dermis about half of cases were positive for CD4+ cells.

D 8+ positive cells on the other hand were seen in the epidermis in 40% cases.  In the upper dermis, all the cases showed CD8+ positive cells.  In the lower dermis, CD8+ positive cells were found in large number of cases.

An immunophenotyping of the inflammation of psoriasiform lesions showing, CD4+ cells as predominant cells in the upper dermis. In lower dermis area showed 16% cases having CD4+ cells.

Various studies have shown that CD4+ cells are less frequent in psoriatic epidermis. In epidermis CD8+ cells were seen in 40% cases, and 8% in psoriasiform lesions. The difference was statistically significant.  In the upper dermis, one study has shown the mixtures of CD4+ and CD8+ T-cells in psoriasis, whereas psoriasiform group showed that CD4+ cells in abundance.

The difference in amount and pattern of CD4+ and CD8+ T-cells in the various compartments is helpful in differentiating between psoriasis and psoriasiform lesions especially in cases with borderline morphology.6

 Conclusion

Psoriasis, the prototype of psoriasiform dermatitis, is a genetically determined, inflammatory, and proliferative disease of the skin characterized by dull red, sharply demarcated scaly plaques. The two clinical signs, Auspitzs sign and the Grattage test have been described as pathognomonic of psoriasis when biopsy is not done.  However, these signs are present only in untreated patients. Psoriasis has many different clinical differentials as other psoriasiform lesions. Besides, the same patient can present at different times with a different clinical presentation.  Since satisfactory management of the condition requires both symptomatic and specific therapy, it is essential to reach a definitive diagnosis. The recurrent nature and prognosis of psoriasis differs from that of psoriasiform dermatitis, thus, further highlighting the importance of reaching the correct diagnosis. Clinical features, considered alone, may not be reliable. Histopathology is regarded as a gold standard for the diagnosis of most dermatological conditions including psoriasis and constitutes definite hard evidence, which can be preserved for future review.  Though to give a precise diagnosis one relies on clinical correlation, histopathology is essential as it is possible to assign specific diagnosis in most cases with a logical and systematic histopathological approach.  In selected cases morphometry, Ki-67 & Cyklin D1, pRb and p53 immunostaining of keratinocytes can be added when needed. The pattern of T-cell infiltrate by immunophenotyping can give an additional diagnostic clue.

Acknowledgement

The authors are grateful to Faisal Kabir Taj for his help in preparing the figure 1.

 References

  1. Jayalakshmy PL, Babitha AM, Sankar S, Nandakumar G. Histopathological spectrum of Psoriasiform dermatitis. Journal of Pathology of Nepal 2016; 6(12): 975 -980.
  2. Tirumalae R . PsoriasiformDermatoses: Microscopic Approach,Indian J Dermatol. 2013 58(4): 290–293. doi: 4103/0019-5154.113945.
  3. Shirish S. Chanadanwale, Narayanan K. Panicker, Sushmah P. Kulkarni, Komal R. Shah, Kumar H, Yugal K. Sharma1, Sukanya Pal, Morphometry analysis of psoriasis and psoriasiform dermatitis: A retrospective study of 50 cases.  Medical Journal of  D.Y. Patil University 2015; 8(1): 43-47.
  4. Sezer E, Böer-Auer A, Cetin E, Tokat F, Durmaz E, Sahin S and Ince U. Diagnostic utility of Ki-67 and Cyclin D1 immunostaining in differentiation of psoriasis vs. other psoriasiform dermatitis. Dermatol Pract Concept. 2015;5(3): 7-13. 2015;5(3):2ul; 5(3):doi: 5826/dpc.0503a02.
  5. Kim SA, Ryu Y W, Kown J I, Choe M S, Jung J W, Cho J W. Differential expression of cyclin D1, Ki‑67, pRb, and p53 in psoriatic skin lesions and normal skin. MolecularMedicine  Reports 2018;17: 735-742,   DOI: 10.3892/mmr.2017.8015.
  6. Rana S, Zeeba J S, Sujata J, Madhur K: A comparative study of psoriasis and psoriasiform lesion on basis of CD4 and CD8 cell infiltration. Our Dermatol Online. 2012; 3(4): 292-297.
  7. Cowden A., Van Voorhees A.S. (2008) Introduction: History of psoriasis and psoriasis therapy. In: Weinberg J.M. (eds) Treatment of Psoriasis. Milestones in Drug Therapy. Birkhäuser Basel, pp 1-2. DOIhttps: doi.org/10.1007/978-3-7643-7724-3_1.
  8. Langley R G B, Krueger G G, Griffiths C E M, Psoriasis: Epidemiology, Clinical Features, and Quality of Life. Ann Rheum Dis. 2005;64(Suppl II):ii18 23.doi: 10.1136/ard.2004.033217.
  9. Grace W. Kimmel and Mark Lebwohl. Psoriasis: Overview and Diagnosis.Bhutani T et al. (eds.), Evidence-Based Psoriasis, Upsoriasiformdermatitisates in Clinical Dermatology, https://doi.org/10.1007/978-3-319-90107-7_1.
  10. Khan ZA, Malik LM,  Jahangir M,  Prevalence of smoking, alcohol, and comorbid conditions in psoriasis. Journal of Pakistan Association of Dermatologists 2010; 20:212-216.
  11. Sako E, Famenini S, Jashin J Wu.  Trends in Type of Original Psoriasis Publications by Decade, 1960 to 2010.   Perm J 2016 Fall;20(4):15-060. http://dx.doi.org/10.7812/TPP/15-060.
  12. Armstrong AW, Harskamp CT, Armstrong EJ. The association between psoriasis and obesity: a systematic review and meta-analysis of observational studies. Nutrition and Diabetes (2012) 2, e54; doi:10.1038/nutd.2012.26..
  13. Samuel T. Hwang, Nijsten T and Elder J T. Recent Highlights in Psoriasis ResearchJournal of Investigative Dermatology 2017; 137(3):550 -556; doi:10.1016/j.jid.2016.11.007.
  14. Busse K, Liao W.Which Psoriasis Patients Develop Psoriatic Arthritis? Psoriasis Forum. 2010; 16(4): 17–25.
  15. Ayala-Fontánez N,  Soler D C, McCormick TS.   Current Knowledge on Psoriasis and Autoimmune Diseases.    Psoriasis: Targets and Therapy 2016;6: 7–32;.org/10.2147/PTT.S64950.
  16. Benhadou F, Mintoff D, Schnebert B, Thio H B. Psoriasis and Microbiota: A Systematic Review. Diseases 2018, 6, 47; doi:10.3390/diseases6020047.
  17. Capon F. The Genetic Basis of Psoriasis. Int J Mol Sci. 2017;18(12):2526. Published 2017 Nov 25. doi:10.3390/ijms18122526.
  18. Mobini N, Toussaint S, Kamino H: Noninfectious Erythematous, Papular, and Squamous diseases. In Lever’s Histopathology of the Skin, 10 th Edition. Edited by Elder DE, Elenitsas R, Johnson BL, Murphy GF, Xu X.  India, Woltrs Kluwer, 2009, pp 169-203.
  19. Flatz L, Conrad C. T-cell-mediated inflammation in psoriasis: pathogenesis and targeted therapy.Psoriasis: Targets and Therapy 2013; 3:1-10. org/10.2147/PTT.S26339.
  20. GuptaS,  KaurM,  Gupta R, SinghS, PantL, SinghP P.Dermal Vasculture in Psoriasis and Psoriasiform dermatitis: a  Morphometric study. Indian J Dermatol. 2011 Nov-Dec; 56(6): 647–649. doi: 10.4103/0019-5154.91820: 10.4103/0019-5154.91820
  21. Mehta S, Singal A, Bhattacharya SN. A  study of clinicohistopathological correlation in patients of  psoriasis and psoriasiform dermatitis. Indian J Dermatol Venereol Leprol 2009;75:100.
  22. Baran W, Szepietowski J. C, Szybejko-Machaj G. Expression of p53 protein in psoriasis. Acta Dermatoven APA 2005;14(3):79-83.
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jhc-2019-jul-v-3-n-2-histopathological-huq-n

Histopathological Pattern of Central Nervous System Infection: Experience of 61 cases at Referral Neuroscience Hospital in Bangladesh

 Huq N,1 Haque ME,2 Jahan N,3 Yusuf MA,4 Baqui MN,5 Rozhana S,6 Shirin S,7 Islam MN8

Abstract

Background: Central nervous system (CNS) infections presenting as space occupying lesions are not uncommon in a developing country like Bangladesh.
Objective: The purpose of the present study was to see the histomorphological pattern of CNS infections.
Methodology: This retrospective study was carried out in the Department of Neuropathology at National Institute of Neurosciences & Hospital (NINS&H), Dhaka, Bangladesh during the time period of June 2013 to March 2018 for a period of around five (05) years. All the patients biopsied in neurosurgical department and was reported as infectious lesions from the Department of Neuropathology of NINS&H were selected as study population.
Result: A total number of 2504 cases of surgical specimens were reported during the study period of which 61(2.4%) cases were infectious lesions. Among 61 infectious cases tubercular lesion, suppurative and fungal causes of infection were found in 33(54.1%) cases, 21(34.4%) cases and 7(11.5%) cases respectively. Majority of the study population was in less than 40 years of age group which was 48(80.0%) cases. Male was predominant than female which was 38(62.3%) cases and 23(37.7%) cases respectively.
Conclusion: In conclusion tubercular infection is the most common CNS infection followed by suppurative and fungal infection.

[Journal of Histopathology and Cytopathology, 2019 Jul; 3 (2):143-150]

Key words: CNS infection, Tuberculosis, Fungal infection

  1. *Dr. Naila Huq, Associate Professor, Department of Neuropathology, National Institute of Neurosciences & Hospital, Dhaka, Bangladesh. nailahuqpopy@gmail.com
  2. Mohammad Enamul Haque, Senior Consultant, Victoria Hospital, Narayanganj, Bangladesh. doctorenamk43@gmail.com
  3. Nasreen Jahan, Research assistant, National Institute of Neurosciences & Hospital, Dhaka, Bangladesh.dr.nasreen2014@gmail.com
  4. Md. Abdullah Yusuf, Assistant Professor, Department of Microbiology, National Institute of Neurosciences & Hospital, Dhaka, Bangladesh. ayusuf75@yahoo.com
  5. Nazmul Baqui, Senior Lecturer, Unit of Pathology, Faculty of Medicine, AIMST University, Kedah, Malaysia. doctornazmul@yahoo.com
  6. Sharmin Rozhana, Lecturer, Unit of Microbiology, Faculty of Medicine, AIMST University, Kedah, Malaysia. srozhana@gmail.com
  7. Sadia Shirin, Medical Officer, Department of Neuropathology, National Institute of Neurosciences & Hospital, Dhaka, Bangladesh. sadiashirin77@gmail.com
  8. Md. Nowfel Islam, Professor & Head, Department of Pathology, National Institute of Neurosciences & Hospital, Dhaka, Bangladesh. nowfel2008@gmail.com

 *For correspondence

 Introduction

Top of FormBottom of FormDiseases causing multiple ring enhancing lesions of the brain are infectious, neoplastic, inflammatory or vascular origin.1-3 Central nervous system (CNS) infections are important because of many emerging and reemerging pathogens. Now a day’s persons are at increased risk of CNS infection due to acquired immunodeficiency syndrome (AIDS). CNS becomes a watershed for Human Immunodeficiency Virus (HIV) infection.4 Infections are also common among the recipients of organ transplantation.2-5 Infections are caused by a wide variety of organisms including bacteria, fungi, parasite and virus. Environmental factors in tropical countries play a significant role in the pathogenesis of CNS fungal infections. Immunocompromised patients are commonly susceptible to fungal infection.5 But exposure to drug or contaminated devices can also cause CNS fungal infection in immunocompetent person. Even People of endemic region can get CNS infection following heavy exposure to fungi.4, 6

Radiology is not always helpful for the diagnosis of CNS infection. Some treatable infectious diseases can even mimic the MRI features of demyelinating disease like multiple sclerosis.3,7,5 Although neoplasms are the common considerations in the presence of enhancing lesions with perilesional edema and mass effect on neuroimaging; non-neoplastic conditions particularly, infectious lesions can have similar imaging characteristics.1

Histopathological diagnosis is essential in case of neoplasm for diagnosis, grading as well as treatment. But infectious lesions that could not be diagnosed by noninvasive procedure also need biopsy. Distinguishing non-neoplastic from neoplastic lesion is extremely important to relieve the patient from the potential side effect of chemotherapy and radiotherapy.3 On the other hand, though brain infections are rare but due to limited space and involvement of vital areas they are associated with high morbidity and mortality.2,8

As Bangladesh has conservative society; HIV infection is not so common. However, like other part of the world, Bangladesh deals with a considerable number of patients having organ transplantation. Moreover, it is one of the densely populated countries of the world. Communicable diseases impose heavy burden on health care system. Tuberculosis is an emerging global health problem. In a country with huge population burden, poor hygiene, malnutrition, less health awareness of people, tuberculosis as well as other infections with involvement of CNS is not rare. There are a very few study regarding the frequency or prevalence of CNS infection in Bangladesh. This study was focused on the frequency and distribution pattern of CNS infections in Bangladesh.

 Methods

The present retrospective study was based on the data collected from the Department of Neuropathology NINS&H, Dhaka, Bangladesh during the time period of June 2013 to March 2018 for a period of around five (05) years. In this study the data of the patients who were underwent CNS surgery and histopathologically diagnosed as infectious lesions were collected. Cases of meningitis were not included in this study as diagnosis of meningitis based only on CSF examination. All extra-cranial skin, soft tissue and bony infectious lesions were excluded from this study. Specimens were stained by routine Hematoxyline & Eosin (H&E) stain. Furthermore, Zeihl-Neelsen stain was performed in all cases of tuberculosis. Periodic Acid Schiff (PAS) stain was done in all cases of fungal infection. Statistical analyses were performed by Statistical Package for Social Science (SPSS) software, versions 22.0 (IBM SPSS Statistics for Windows, Version 22.0. Armonk, NY: IBM Corp.). Continuous data that were normally distributed were summarized in terms of the mean, standard deviation and minimum, maximum. Categorical or discrete data were summarized in terms of frequency and percentages.

 Result

A total number of 2504 cases of surgical CNS specimens were reported during the study period of which 61(2.4%) cases were infectious lesions. Only cases of infectious lesions were further analyzed. The age range of patients was 9 months to 85 years. The patients were stratified into 4 groups which were less than 20 years, 20 to 40 years, 40 to 60 years and more than 60 years. Most of the patients belong to 20 to 40 years age group which was 26(42.6%) cases followed by less than 20 years which was 23(37.7%) cases. CNS infection was very rare in more than 60 years of age; only two cases were found in this age group. However, male predominance with a male to female ratio of 1.7:1 was seen. Male was 38(62.3%) cases and female 23(37.7%) cases respectively (Table I).

In 61.0% cases of histologically diagnosed CNS infections radiological diagnosis were tumors. However in 39.0% cases radiological diagnosis was infection which correlates with the histological diagnosis. In 19 cases radiological diagnosis correlates with the histopathological diagnosis and all of them were tubercular lesion. Radiological diagnosis did not correlate with histopathological diagnosis in 32 cases. And radiology was not available in 10 cases.

 

Of the total 61 cases 33(54.1%) cases were tubercular, 21(34.4%) cases were suppurative and 7(11.5%) cases were fungal infection. AFB stain done in 30 cases of tuberculosis and result was negative. All cases of fungal infection were further stained by PAS stain and found positive.

 Discussion

CNS includes a wide variety of diseases ranging from suppurative, tubercular, fungal, parasitic and viral infection. For the diagnosis of these cases combined approach of clinical, radiological, CSF and histopathological examination are necessary. There is a scarcity of research works related to the pattern of CNS infections in Bangladesh. As National Institute of Neurosciences & Hospital (NINS&H) is a tertiary level referral hospital in Bangladesh, it deals with different neurological diseases having a well-developed neurosurgery department. Therefore, a great number of patients attend in this hospital.

CNS infection producing space occupying lesions are not uncommon in Bangladesh. About 2.4% of surgical specimens of this study belong to infectious lesions. The age range of the study population was 9 months to 85 years with highest percentage 42.6% cases between 2nd to 4th decades, followed by 37.7% cases in less than 20 years. CNS infection was very rare in more than 60 years of age; only two cases found in this group. The age distribution is consistent with most of the previous studies conducted in different parts of India.9,10,11 In our study 62.3% cases were male and the male to female ratio was 1.7:1. A male predominance seen in most of the reported studies indicating that male are more prone to these infections.9,10,11 This may be due to more exposure of the male of this age group to the environmental agents, vectors due to their outward activities.9 Some zoonotic infections like Neurobrucellosis occur due to occupational exposure.12 Moreover, in the developing countries male got priority over the female in getting treatment facilities.9 This observation matches with Bangladesh having the similar socioeconomic pattern.

We analyzed the anatomical location of the total 61 cases. It has been observed that most of the cases 49(80.0%) were cranial and 12(20.0%) cases were in spinal location. The percentage could be different if lesion like Pott’s disease would include in the study. Rosenblum5 has reported that 20.0% of brain abscess are not associated with predisposing bacterial infection; however, remaining results are from established pyogenic infection in extraneural site. Contiguous spread of infection can result from sinusitis, otitis, dental sepsis and pyogenic infection of face and scalp which causes intracerebral abscess or subdural empyema.5 Contamination of the CNS can occur in three routes. Arterial route is the main route of contamination and the disposition of intracerebral arterial division causes development of diseases in this way at the junction of white matter and gray matter or in the territory of perforating artery. Therefore, frontal or temporal region lesion is most common. Spinal anomalies predispose to intramedullary abscess but such infections are extremely rare5. Herpes simplex, Rabies, Varicella Zoster or a few viruses disseminated through neural route. Direct contamination can result from cranial or vertebral wound or following intracranial surgery. All these explanations suggest that cranial location is more common site of CNS infection particularly in case of acute bacterial infection which is similar to our study.5,8 Another study has been mentioned that infectious lesions in the brain stem are very rare.13

Among 61 cases radiology is not available in 10 cases which are histologically diagnosed as CNS infection. In the remaining, radiological diagnosis correlates with the histopathological diagnosis in 39.0% cases. However, in 61.0% cases radiological diagnosis are tumors. From biostatistical point of view it is not the indicator of sensitivity of radiology. As cases of CNS tumors were not included in the study, it would be a biased statement.

In radiology, neoplasm is the common consideration in enhancing lesions with perilesional edema and mass effect. But infectious lesion, occasionally demyelinating disease can share the similar imaging characteristic1,5. There are some limitations of early imaging and overlapping imaging appearance of many of the infections. Pyogenic abscess often show amino acid at spectroscopy.  Neurotuberculosis, neurosyphilis shows nodular meningeal enhancement with or without vasculitis which can also be seen in fungal infection. Some diseases like, neuro-cysticercosis, echinococcosis may have highly characteristic imaging pattern. But many other infections share common imaging findings. So, a high degree of suspicion is required to assume the diagnosis of CNS infection in radiology.1,14

Of the total 61 cases 54.1% cases are tubercular; 34.4% cases are suppurative and 11.5% fungal. As primary tuberculosis has high prevalence in Bangladesh, CNS tuberculosis might be the commonest presentation in this study. Garg RK3 et al also mentioned intracranial tuberculoma as frequently encountered brain lesion in tropical country. Bacteria are responsible for majority of suppurative infections of CNS and its covering.5 According to working criteria, cases of meningitis are not included in this study. Pyogenic abscess is the second common presentation (34.4% ). Our study is limited by non-availability of relevant microbiological analysis. So type of organism producing pyogenic abscess could not be determined from this study.

We found 7 cases of fungal infection. One of them was suffering from rheumatoid arthritis and receiving treatment with methotrexate. And another was a baby of 9 monthsage. Rest of the patients has no known history of immunodeficiency. Incase of fungal infection we found highest incidence of aspergillosis(4) followed by zygomycosis(2). Only one case of phaeohyphomycosis was found. A hospital based study of India also shows increased incidence of hyphal form like aspergillosis and Zygomycosis in non immunocompromised host.15The cryptococcus usually causes meningitis and rarely presentas cryptococcoma.16,17 Therefore, the cryptococcus is not found in this study.

CNS parasitoses include a great variety of protozoa and helminth.5,17 We did not find any case of neurocysticercosis, toxoplasmosis, echinococcosis, malaria, schistosomiasis and also rare amoebic infection of CNS. A study in India by Bhalla et al9 showed that these infections produce intracranial mass lesion in HIV positive patients. An HIV infected patient having CD4 cell count less than 200 cells/µL is at high risk for opportunistic brain infection. HIV infection is not so common in Bangladesh in comparison with other South Asian country like India or Thailand. As patients of HIV get treatment only in Infectious Disease Hospital (IDH) of Bangladesh, the data of those patients could not be included in this study. These infections may be less frequent in our environment or poor access of our people to the tertiary level hospital like NINS&H may result such outcome. As most of the affected people belong to lower socioeconomic condition the people may die before reaching the health care system. Another study in India showed that some of these infections of nervous system diagnosed mostly in autopsy specimen.5,18 A study in Hill tracts of Bangladesh; endemic for malaria showed significant cases of cerebral malaria in autopsy specimens.19 As facilities of autopsy are not available in our institute the study might be missing these infections.


Conclusion

Tubercular infection is the most common CNS infection followed by suppurative and fungal infection in biopsied specimen. Less than 40 years age group is the most vulnerable age group. High clinical suspicion, awareness of imaging pattern and microbiological approach can minimize the need for brain biopsy. Further large scale multi-institutional study including autopsy should be carried out.

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  12. Algahtani H, Shirah B, Abdulghani D, Farhan R, and Algahtani R,Occapational Neurobrucellosis Mimicking a Brain Tumor: A Case Report and Review of the Literature in Case Report in infectious Diseases ;Volume 2017, Article ID 1434051:1-5
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  14. Robert Y. Shih LTC, Kelly K. Koellar, MD Bacterial, Fungal and Parasitic Infections of the Central Nervous System: Radiologic-Pathologic correlation and Historical perspectives. Radiographics 2015;35(4)4:1141-1169
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