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Angiolipoma of Stomach: A Case Report


Angiolipoma of Stomach: A Case Report

 *Jahan JA,1 Akhter S,2  Kamal M,3 Karim SS4

 Abstract

Angiolipoma is a variant of benign lipomatous tumors and generally found in subcutaneous tissues. The tumor is rarely found in gastrointestinal tract. We present a case of a 55-year-old male who presented with melena. Endoscopy of upper gastrointestinal tract showed a polypoid mass, while abdominal CT scan suggested a submucosal lipoma. After partial gastrectomy,  histological examination of the tumor revealed an encapsulated nodule composed of mature fatty tissue, fibrous tissue and small blood vessels, and accordingly the lesion was diagnosed as angiolipoma.

  [Journal of Histopathology and Cytopathology, 2018 Jan; 2 (1):63-67]

Key words:  Angiolipoma, Stomach

 

  1. *Dr. Jasmine Akhter Jahan, Resident,  Department of  Pathology, Bangabandhu Sheikh Mujib Medical University, Dhaka. drjasmine30@gmail.com
  2. Shabnam Akhter, Associate Professor, Department of  Pathology, Bangabandhu Sheikh Mujib Medical University, Dhaka.
  3. Professor Mohammed Kamal, Professor, Department of Pathology, Bangabandhu Sheikh Mujib Medical University, Dhaka.
  4. Syed Sirajul Karim, Department of Surgery, Bangabandhu Sheikh Mujib Medical University, Dhaka.

 

* For correspondence.

 Introduction

Angiolipoma is one of the benign adipocytic tumors that usually occur in subcutaneous tissues.1  The tumor is composed of adipose tissue and proliferating blood vessels. It is commonly found in subcutaneous tissues of the trunk and extremities.2  Although endoscopic and radiologic examination may provide helpful information, the final diagnosis of angiolipoma relies on histopathological features of excised specimen.3

Case report

A 55-year-old male patient was admitted in a private hospital in  Dhaka with the complaints of gastric mass, melena and generalized weakness. His symptoms had begun 20 days back and he experienced bloody stool with foul smell, which had lasted for seven days. Initially he visited an outside hospital, where he was diagnosed as a severely anaemic patient. His laboratory test results were as follows: hemoglobin level 7.8 g/dl, red blood cell count  2.78 × 1012/L, white blood cell count 13× 109/L, neutrophil count 74% and erythrocyte sedimentation rate (ESR) 82 mm in first hour. He was admitted in that hospital for blood transfusion because of his severe anemia and 2 units of fresh whole blood were transfused. Further investigation including complete metabolic panel, liver function tests, serum ferritin,  urinalysis and stool culture were all found within normal limit. Ultrasound of whole abdomen was also performed, which showed fatty infiltration in the liver (Grade-1). Endoscopy of upper gastro-intestinal tract revealed a polypoid mass in the gastric antrum with smooth surface and evidence of recent bleeding (Fig. 1).

The esophagus and duodenum appeared normal. Biopsy of the lesion showed massive necrosis and fibrinous exudate. After the blood transfusions when the patient became hemodynamically stable, he was discharged on request. Later the patient got admitted into Bangabandhu Sheikh Mujib Medical University with melena, cough and fever for definitive treatment. On arrival his abdomen was soft and non-distended. The patient’s past medical history was occasional dyspepsia for one year which was relieved by antacids. The family history was unremarkable. Repeat laboratory tests showed haemoglobin level of 11.6 g/dl, red blood cell count of 4.15 × 1012/L, white blood cell count of 9.0× 109/L,  neutrophil count of 67% and erythrocyte sedimentation rate (ESR) of 60 mm in 1st hour. A complete biochemical panel, serum albumin, fasting blood sugar, complete urine analysis, chest X-ray, electrocardiography (ECG) and echocardiography were all normal. An abdominal CT scan with contrast showed a well defined almost rounded fat density area measuring about 4.1 cm x 3.9 cm in the lumen of pyloric and antral part of stomach appeared to be arising from posterior wall, suggestive of submucosal lipoma at pyloric and antral part of stomach (Fig. 2). Tiny calcification is seen in hepatic parenchyma. Accordingly the patient was operated. A large antral growth was found and distal partial gastrectomy with gastrojejunostomy was performed. The patient recovered from surgery without complication. The specimen was sent to the department of pathology where gross examination showed a 5 × 5 × 3 cm polypoid tumor on the lesser curvature and posterior surface in the antrum  (Fig. 3). Three lymph nodes ranging from 02 mm to 04 mm were identified. Histologic examination revealed a tumor composed of lobules of fatty tissue with intervening fibrous tissue and small thin walled blood vessels  (Fig. 4 and 5). Mucosal ulceration was present. Lymph nodes showed reactive changes with no evidence of tumor. The final pathologic diagnosis was angiolipoma of the stomach. During follow-up, this patient showed no recurrence.

 

 

 

 

 

 

 

Fig 1.  Endoscopic appearance of the gastric polypoid mass.

 

 

 

 

 

 

Fig 2.   CT scan of abdomen showing gastric mass with low intensity in the centre (arrow)

 

 

 

 

 

Fig 3. Specimen of stomach showing mass with yellow fatty core (P) and normal mucosa (M).

 

 

 

 

 

Fig 4.  Histological section of stomach showing angiolipoma (T) and normal mucosa (M) (H&E x120)

 

 

 

 

 

 

Fig 5.   Histological section  showing adepocytes (A), blood vessels (BV) and fibrous tissue (F) (Masson Trichrome x220)

Discussion

Angiolipoma is a benign adipocytic tumour, usually arising in subcutaneous tissue. It is composed of adipose tissue and proliferating blood vessels.2 Most common site of angiolipoma are the extremities. It also involves subcutaneous tissue of trunk. Angiolipomas usually appear in the late teens or early twenties and has a male predominance.1

Angiolipoma was first defined in 1912  by Bowen (cited by Howard).4 The histopathological features of angiolipomas were differentiated from those of lipomas by Howard (1960).5 Clinically angiolipomas usually present with multiple subcutaneous, tender, small nodules in arms and trunk. They are most often less than 2 cm in diameter.1,6 Cytogenetic analysis detected chromosomal aberrations, such as rearrangements of 12q14-15, rearrangements of 6p21-22, or deletions of 13q12-14 and 13q22. The gene involved in 12q14-15 is HMG A2 and in 6p21-22 is HMG A1.7 These aberrant expressions suggest that the pathogenesis of angiolipomas may be different from other lipomas. The tumor in some cases show familial incidence, which is rare (5% of all cases) and have autosomal dominant inheritance.1,8

Grossly, the tumour is well defined, encapsulated and have cut surface which is yellowish to reddish according to the prevalence of fat or vascular component. Morphologically, it is comprised of mature adipose tissue with an interspersed vascular proliferation.1,2  Occasional fibrin thrombi are seen. The tumor can be classified as lipomatous or angiomatous type. This classification is based on the ratio of presence of adipose tissue or vascular tissue (8). The tumor is typically diagnosed with hemotoxylin & eosin stain. The immunohistochemical examination is rarely needed. Angiolipoma shows focal to diffuse positivity for S100 protein in the adipocytes. Also endothelial markers e.g. CD34 and CD31 are positive in the vascular component.2

Angiolipoma in the gastrointestinal tract is very rare and  seen mostly in the colon.9, 10  Twenty two cases of angiolipoma involving the gastrointestinal tract have been reported in the literature up to 2013. Among them, four cases were in the stomach. The antrum is the common site for gastric angiolipoma. Other involved areas are oesophagus, duodenum, small intestine, colon and rectum.9, 2

Patients with angiolipoma in the gastrointestinal tract are usually asymptomatic. Some may present with indigestion, abdominal discomfort, abdominal pain, GI bleeding and anaemia, symptoms of intussusceptions or obstruction with increasing size of the tumor .2, 9, 10 Submucosal polypoid mass lesion is typically found in upper GI endoscopy. Histologically, angiolipoma in the stomach is composed of mature fatty tissue and proliferating blood vessels. Fibrin thrombus is rarely seen in gastric angiolipoma and other nonsubcutaneous angiolipomas, in contrast to cutaneous angiolipomas.2, 10

Diagnosis of angiolipomas in the gastrointestinal tract can be made by radiological examination via barium radiograph, abdominal ultrasound, abdominal computed tomography (CT) or magnetic resonance imaging (MRI) before polypectomy or resection. A filling-defect in lumen by barium enema and a hyperechoic lesion on transabdominal ultrasound. Abdominal computed tomography (CT) image may show variable findings depending on tissue components of the lesion. This has an appearance from high-density mass due to lipomatous component to heterogeneous lesion with mixed fatty and soft tissue density.2, 9 The final diagnosis is confirmed by histopathological examination.2,8,9

The pre-operative diagnostic accuracy for gastric angiolipomas is quite low. So the correct diagnosis is usually made intraoperatively and confirmed by histopathology.9 The treatment options depend on the type of the lesion. It varies from polypectomy of small pedunculated lesions to surgical excision of large mass. After complete excision, the tumor typically does not recur.2

The angiolipoma in our case presented with melena and anaemia requiring whole blood  transfusion. Endoscopy revealed polypoid mass with recent bleeding. As the lesion was submucosal, endoscopic biopsy failed to diagnose the tumour. A well circumscribed submucosal lipoma was identified on abdominal CT scan. After distal partial gastrectomy, final diagnosis  of gastric angiolipoma was made by histopathological examination by its typical morphological features.

Conclusion

Angiolipoma is a benign tumor, commonly occurring in subcutaneous tissue but rare in gastrointestinal tract. It is important to remember that submucosal polypoid lesions in GI tract with or without symptoms can be an angiolipoma, although it is quite rare.

 References

  1. Christopher DM, Fletcher C, Bridge JA, Hogendoorn PCW, Mertens F. WHO classification of Tumours of Soft Tissue and Bone. 4th ed.: IARC Press; 2013.
  2. Liu YJ, Karamchandani DM. Gastric Angiolipoma, a rare entity. Arch Pathol Lab Med. 2017; 141: 862-866.
  3. Chen YY and Soon MS. Preoperative diagnosis of colonic angiolipoma. World J Gastroenterol, 2005; 11(32): 5087-5089.
  4. Hang Y. and Zhu CQ. Angiolipoma of the colon. Journal of Digestive Diseases, 2014; 15: 154-157.
  5. Howard WR, Elson MC, Helwig B. Arch Dermatol, 1960; 82(6):924-931.
  6. Rogy MA, Mirza D, Berlakovich G, Winkelbauer F, Rauhs R. Submucous large-bowel lipomas: presentation and management. An 18-year study. Eur J Surg, 1991; 157(1): 51-55.
  7. Rosai J. Rosai and Ackerman’s Surgical Pathology. 10th ed.: Elsevier; 2011.
  8. Kacar S, Kuran S, Temucin T, Odemis B, Karadeniz N, Sasmaz N. Rectal angiolipoma: A case report and review of literature. World Journal of Gastroenterology, 2007; 13(9): 1460-1465.
  9. Wang L, Chen P, Zong L, Wang GY, Wang H. Colon angiolipoma with intussusception: a case report and literature review. World Journal of Surgical Oncology. 2013; 11: p. 69.
  10. Nam YH, Park SC, Kim HJ, Lee SW, Kim J, Choi DH, et al. Angiolipoma of the stomach presenting with anaemia. Przeglad Gastroenterologiczny. 2014; 9(6): 371-374.

 

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Rising Trend of Adenocarcinoma of Cervix: A Global Perspective


Rising Trend of Adenocarcinoma of Cervix: A Global Perspective

*Akhter S,1 Khatun S2

 Abstract

Worldwide incidence of invasive cervical cancer including squamous cell carcinoma has been decreasing for the last 40 years, but incidence of adenocarcinoma of cervix shows a steady increase. This increase is mostly reported from the developed countries with organised cancer screening system and cancer registries. Human papillomavirus (HPV) has been established as the most important etiological factor for cervical cancers including adenocarcinoma. This review article discussed the epidemiological data from several articles including meta-analyses and international projects to give an overview of the increasing incidence of cervical adenocarcinoma throughout the world. The article then delved into the epidemiological studies that provided data regarding association of HPV with adenocarcinoma of cervix. It is evident from these studies that HPV types 16, 18 and 45 are responsible for more than 90% of adenocarcinoma of cervix. Differences in type specific HPV prevalence among countries might be the reason for the variation in the incidences of adenocarcinoma of cervix from region to region. The rising trend in the incidence of cervical adenocarcinoma can be explained as a cohort effect related to increased exposure to prevalent HPV infection in younger women, and also to less effective performance of cytology screening methods in detecting glandular lesions of cervix. In this context, the currently available prophylactic vaccines against HPV should come in the frontier to prevent occurrences of invasive cervical cancer including adenocarcinoma worldwide.

[Journal of Histopathology and Cytopathology, 2018 Jan; 2 (1):56-62]

 Key words: Cervical cancer, Adenocarcinoma, Incidence, Human papillomavirus

 

  1. *Dr. Shabnam Akhter, Associate Professor of Pathology, Bangabandhu Sheikh Mujib Medical University, Dhaka. akhtershabnam66@gmail.com
  2. Shahana Khatun, Assistant Professor of Pathology, MH Samorita Hospital and Medical College, Dhaka

*For correspondence

 

Introduction

Worldwide incidence of invasive cervical cancer has been decreasing over the last 40 years owing to organised as well as opportunistic practices of cytology screening mostly in the developed countries.  Majority of cervical cancers are squamous cell carcinomas (SCC), while adenocarcinomas (ADC) are small in number. There is no doubt that cytology screening programs have lead to increased detection and early management of precursor lesions of cervical carcinoma. However, despite the decline in overall incidence of cervical cancer, several studies have reported increasing incidence of cervical ADC in comparison to SCC, particularly among younger women and mostly in the developed countries since the 1970’s.1-6

When German virologist Harold zur Hausen and his team, after their extensive works from 1972 to 1984, revealed their revolutionary discovery that human papillomavirus (HPV), notably HPV 16 and HPV 18, are causative agents of cervical cancer, subsequent researches related to cervical cancer were directed towards HPV. Several years later, Bosch et al. (1995)7 reported from their international survey that 93% of cervical cancers contained HPV DNA. They also found that the prevalence of HPV did not show variation between histologic subtypes of cervical cancer (SCC, ADC and adenosquamous carcinomas). By 1999, Walboomers et al.8 published their seminal studyfindings that the prevalence of HPV in cervical cancers was 99.7% worldwide, thus proclaiming that infection with high-risk HPV was central to the pathogenesis of almost all cervical cancers.

With this background this review article will give an overview of the changing trend of cervical ADC from the data provided by epidemiological studies. The studies are mostly from the developed countries of North America and Europe, while few international works have also included data from underdeveloped countries of Asia, Africa and South America.3,9 In the latter half of the article, the etiological aspect of cervical ADC will be discussed, that will include the role of HPV and other risk factors identified so far.

 Rising trend of adenocarcinoma of cervix

Peters et al.1 reported in 1986 about increase in the proportional incidence of ADC of the cervix during 1972-1982 among white women aged less than 35 years in Los Angeles County, California. The authors’ thought that this was due to use of oral contraceptives before the age of 20 years. Being intrigued by such observation, Schwartz and Weiss2 followed the rates of invasive cervical cancer by age, time period and histologic types between 1973 and 1982 among 8,647 women identified by the SEER (The Surveillance, Epidemiology, and End Results) program registries. They found that the incidence of ADC of the cervix in women under the age of 35 years had increased more than twofold between 1973 and 1982. They speculated that other potential risk factors related to sexual behaviour were also to be considered, as for example, in young women early age at first intercourse or increased number of sexual partners concurred with the early use of oral contraceptives.

Vizcaino et al. (1998)3 conducted a study with International Agency for Research on Cancer (IARC) to find out the time trends in the incidence of cervical ADC, particularly in young women. They collected incidence data on ADC and adenosquamous cell carcinoma during the period 1973-1991 from 60 population-based cancer registries of 32 defined populations in 25 countries. Their analyses focused three aspects of the incidence trend: age, calendar period of diagnosis and birth cohort. The final results reported a significant increase in incidence among women born after 1930 in the United States (white and Hispanic women), Canada, Australia, United Kingdom, Denmark, Sweden, Slovakia and Slovenia. Increasing trend was also observed in Bombay (Mumbai, India), in Japan (Osaka) and among Chinese women in Singapore. The analyses also showed that besides age, the increasing incidence was found related to year of birth, with each successive cohort showing higher risk at a given age compared with their precedent cohorts. However, a decreasing trend was also observed in Finland, France and Italy, and no significant changes in incidence were found in several other countries. The authors concluded that part of the increase might be due to an increasing prevalence of HPV infection and partly to increased detection of atypical glandular lesions by cytology screening.3

Later, Smith et al. (2000)4 used the SEER (The Surveillance, Epidemiology, and End Results) database to identify all cases of cervical cancer registered from 1973 to 1996 with the objective to find out the trends in the age-adjusted incidence of ADC of the uterine cervix relative to SCC in the United States. Their results showed that over 24 years the age-adjusted incidence rates decreased for all invasive cervical cancers by 36.9% and for SCC by 41.9%, but increased for ADC by 29.1%. The percentage of SCC relative to all cervical cancer had decreased from 76.21% (between 1973 and 1977) to 70.17% (between 1993 and 1996). On the other hand, percentage of ADC had increased from 12.4% (1973-1977) to 24.2% (1993-1996). The findings were all in favour of the fact that the absolute frequency as well as the relative frequency of ADC showing a rising trend.4

Subsequently Bray et al. (2005)5 carried out a study to examine the secular trends in the incidence of ADC of cervix in women ages <75 in 13 European countries using an age-period-cohort- model. The study reported that age-adjusted ADC incidence rates had increased throughout Europe, the rate of increase ranging from around 0.5% per year in Denmark, Sweden, and Switzerland to ≤3% in Finland, Slovakia and Slovenia. The increases were calculated first to affect generations born in the early 1930s through the mid-1940s, with risk rising in women born in the mid-1960s relative to those born 20 years earlier.5

Bulk et al. (2005)6 of Netherlands did a population-based study on the incidence of invasive cervical cancer to evaluate trends in relation to age at time of diagnosis. The cases were collected from the Netherlands Cancer Registry for all women with invasive cervical cancer between 1989 and 1998. The results depicted that in this 10-year period, the incidence of SCC had decreased substantially from 7.1/100,000 to 6.1/100,000, and the incidence of ADC overall remained static, but it had increased in women aged 15-29 and in women aged 30-44.6

 Etiological factors related to adenocarcinoma of cervix

ADC of cervix, like SCC, has been reported to be associated with high-risk HPV infection, which is considered to play the central role in cervical carcinogenesis.7-9 So, the etiological factors will be discussed in two parts, the first will be about the association of HPV in ADC of cervix, and the second part will encounter the postulated risk factors other than HPV infection.

 HPV and adenocarcinoma of cervix

With regard to increasing incidence of cervical ADC, Andersson et al. (2000)10 tried to find out the presence of HPV in diagnosed cases of ADC of cervix during 1986-1996, the cases identified through Swedish Cancer Registry. HPV was identified in 71% cases of ADC; in the HPV-positive cases, HPV18 was present in 52% and HPV16 in 33%. They also reported that the prevalence of HPV in ADC differed with age; women <40 years were HPV-positive in 89% of cases, while women ≥60 years were HPV-positive in 43% cases.

Clifford et al. (2003)11 carried out a meta-analysis and reported HPV18 to be the most frequent type (37.7%) in ADC followed by HPV 16 (31.3%) and HPV 45 (5-7%), whereas HPV 16 was the dominant type in SCC of cervix. On the other hand, the population-based study by An et al. (2005)12 in Korea revealed that HPV16 was the most frequent type followed by HPV 18, while overall HPV prevalence in the cervical ADC among Korean women was 90%.

To find out the extent to which HPV and cofactors may be responsible for the increasing trend of cervical ADC, Castellsague et al. (2006)13 examined eight case-control studies during 1985-1997 from eight different countries with differences in the incidence of cervical cancer. Countries were from North Africa, South America and Southeast Asia. They found HPV to be the main risk factor, prevalence ranging from 86% in Paraguay to 100% in Algeria. HPV16 and HPV18 were the most dominant HPV types, together being present in 82% of the cases.

International Collaboration of Epidemiological Studies of Cervical Cancer (2006)14 conducted a collaborative reanalysis from 12 epidemiological studies. Their analyses revealed that HPV16 was the commonest type in both SCC and ADC of cervix. However, HPV16 was more common in SCC (56% versus 40%) whereas HPV18 was more common in ADC (35% versus 16%). Similarly, Smith et al. (2007)15 published their meta-analysis update on HPV type distribution covering six continents where they reported that HPV positivity overall was a little more in SCC (90%) than in ADC (85%), HPV16 was less frequent in ADC (33%) and more frequent in SCC (55%), and HPV18 was the dominant type in ADC (37%) compared with SCC (13%). They also found that HPV 16/18 proportion was higher in Europe, North America and Ocenia (74-77%) than in Africa, Asia and South/Central America (65-70%).

On behalf of the Retrospective International Survey and HPV Time Trends Study Group, Silvia de Sanjose (2010)16 completed an international project with the aim to provide distribution pattern of HPV genotypes in samples of invasive cervical cancer. Samples were collected covering 38 countries from Europe (10), North America (USA), central South America (10), Africa, Australia and Asia (12 including Bangladesh). From the analyses of data, they found that HPV types 16, 18 and 45 were the three most common types in each histological type of SCC, ADC and adenosquamous cell carcinoma of cervix. Both HPV18 and HPV45 were more common in ADC than in SCC. The other intriguing finding was that cancers related to HPV18 and HPV45 occurred at a much younger age (<50 years). The early presentation of invasive cancers in these cases indicates that these virus types possibly require a short time of progression to invasive cancer with a high integration rate into the host genome.

Afterwards, Pirog et al. (2014)17 did a worldwide analysis of HPV prevalence and genotypes in different histological subtypes of cervical ADC. They found that relatively narrow spectrum of high-risk HPV types, HPVs 16, 18 and 45 were present in the vast majority of ADC, together constituting 94.1% of HPV-positive cases. In contrast to the earlier meta-analyses by Clifford et al. (2003)11 and Smith et al. (2007)15, they found HPV16 to be the most frequent type (50.9%) followed by HPV18 (31.6%) and HPV 45 (11.6%) in HPV-positive ADC cases. Though the ratio of HPV16 to HPV18 in ADC varied from study to study, the percentage of combined HPV16 and HPV18-positive cases were found much uniform among studies (75.7-94.8% of cases) with an average of 89.8%.

To find out the HPV subtypes in cervical ADC in women of Bangladesh, Akhter et al. (unpublished data, presented as poster at the Annual meeting of USCAP 2017)18 studied 71 cases of cervical ADC. The results showed that, in contrast to western countries, HPV16 was the most frequent type (63.4%) followed by HPV18 in 16.9%. HPV DNA was detected in 100% cases. These data indicate a significant epidemiological difference in the type-specific prevalence of HPV between the developed and underdeveloped countries.

 Risk factors other than HPV infection

The other risk factors for ADC are more or less similar to those for cervical cancer in general, being related to factors that promote spread of HPV infection from person to person as any other sexually transmitted disease.

Several studies12,14,19-21 have worked with risk factors associated with cervical ADC in comparison to SCC. The notable risk factors other than HPV are described in the following sections.

  1. Lifetime number of sexual partners was reported to show strong association with both SCC and ADC, risk of cancer increasing with the increasing number of partners.12,14,19-21
  2. Earlier age at first intercourse was found to be associated with increased risk of both SCC and ADC of cervix, the association being stronger for SCC.12,14,19-21
  3. Longer duration of use of oral contraceptives was reported to be strongly related to risk for both SCC and ADC.12,14,19-22
  4. Smoking was considered a risk factor for SCC compared to never smokers whereas it was found not to be a risk for adenocarcinoma. 12,14,19-21
  5. High parity showed significant association with both SCC and ADC (three or more live births or full-time pregnancies versus none), the association being stronger for SCC. 12,14,19-21
  6. Herpes simplex virus type 2 (HSV-2) seropositivity was reported to be associated with a more than twofold increase in the risk of cervical ADC.12

 Conclusions

The review discussions have highlighted infection with high-risk HPV as the most important etiological factor for cervical ADC. In terms of type specific prevalence, HPVs 16, 18 and 45 are reported to be responsible for more than 90% of ADC of cervix. Differences in type specific HPV prevalence among countries may be responsible for the variation in the incidences of ADC of cervix from region to region. The rising trend in the incidence of cervical ADC can be explained as a cohort effect related to increased exposure to prevalent HPV infection in younger women, and also to less effective performance of cytology screening methods in detecting glandular lesions of cervix. In this context, the currently available prophylactic vaccines against HPV should come in the frontier to prevent occurrences of invasive cervical cancer including adenocarcinoma of cervix worldwide.

 References

  1. Peters RK, Chao A, Mack TM, et al. Increased frequency of adenocarcinoma of the uterine cervix in young women in Los Angeles County. JNCI 1986; 76:423-8.
  2. Schwartz SM and Weiss NS. Increased incidence of adenocarcinoma of the cervix in young women in the United States. American Journal of Epidemiology 1986;124(6): 1045-47.
  3. Vizcaino AP, Moreno V, Bosch FX, Munoz N, Barros-Dios XM and Parkin DM. IARC. International trends in the incidence of cervical cancer: I. Adenocarcinoma and adenosquamous cell carcinomas. International Journal of Cancer 1998; 75: 536-545.
  4. Smith HO,Tiffany MF, Qualls CR and Key CR. The rising incidence of adenocarcinoma relative to squamous cell carcinoma of the uterine cervix in the United States – A 24-year population-based study. Gynecologic Oncology 2000; 78: 97-105.
  5. Bray F, Carstensen B, Moller H, Zappa M, Zakelj MP, Lawrence G et. al. Incidence trends of adenocarcinoma of the cervix in 13 European countries. Cancer Epidemiol Biomarkers Prev 2005; 14(9): 2191-99.
  6. Bulk S, Visser O, Rozendaal L, Verheijen RH, Meijer CJ. Cervical cancer in the Netherlands 1989-1998: decrease of squamous cell carcinoma in older women, increase of adenocarcinoma in younger women. Int J Cancer 2005; 113:1005-1009
  7. Bosch FX, Manos MM, Munoz N, Sherman M, Jansen AM, Peto J et al. Prevalence of human papillomavirus in cervical cancer: a worldwide perspective. JNCI 1995;87(11):796-802
  8. Walboomers JM, Jacobs MV, Manos MM, Bosch FX, Kummer JA, Shah KV et al. Human papillomavirus is a necessary cause of invasive cervical cancer worldwide. J Pathol 1999; 189(1): 12-19.
  9. Parkin DM and Bray F. Chapter 2: The burden of HPV-related cancers. Vaccine 2006. Doi: 10.1016/j.vaccine.2006.05.111
  10. Andersson S, Rylander E, Larsson B, Strand A, Silfversvard C, Wilander E. The role of human papillomavirus in cervical adenocarcinoma carcinogenesis. European Journal of Cancer 2001;37:246-250.
  11. Clifford GM, Smith JS, Plummer M, Munoz N and Franceschi S. Human papillomavirus types in invasive cervical cancer worldwide: a meta-analysis. Br J Cancer 2003; 88: 63-73.
  12. Castellsague X, Diaz M, Sanjose S, Munoz N, Herrero R, Franceschi S et al. Worldwide human papillomavirus etiology of cervical adenocarcinoma and its cofactors: Implications for screening and prevention. Journal of the National Cancer Institute 2006; 98(5): 303-315
  13. An HJ, Kim KR, Kim IS, Kim DW, Park MH, Park IA et al. Prevalence of human papillomavirus DNA in various histological subtypes of cervical adenocarcinoma: a population-based study. Modern Pathol 2005;18:528-534.
  14. International Collaboration of Epidemiological Studies of Cervical Cancer. Comparison of risk factors for invasive squamous cell carcinoma and adenocarcinoma of the cervix: Collaborative reanalysis of individual data on 8,097 women with squamous cell carcinoma and 1,374 women with adenocarcinoma from 12 epidemiological studies. Int. J. Cancer 2006;120:885-891.
  15. Smith JS, Lindsay L, Hoots B, Keys J, Franceschi S, Winer R. Human papillomavirus type distribution in invasive cervical cancer and high-grade cervical lesions: A meta-analysis update. Int. J. Cancer 2007;121:621-632.
  16. Silvia de Sanjose, Quint WGV, Alemany L, Geraets DT, Klaustermeier JE, Lloveras B et al. on behalf of the Retrospective International Survey and HPV Time Trends Study Group. Human papillomavirus genotype attribution in invasive cervical cancer: a retrospective cross-sectional worldwide study. Lancet Oncol 2010; 11:1048-56.
  17. Pirog EC, Lloveras B, Molijin A, Tous S, Guimera N, Alejo M et al. HPV prevalence and genotypes in different histological subtypes of cervical adenocarcinoma, a worldwide analysis of 760 cases. Modern Pathol 2014; 27: 1559-67.
  18. Akhter S, Kamal M, Barua AR, Sung CJ, Lawrence WD, Quddus MR. Adenocarcinoma of cervix is surging: Is high-risk HPV subtype(s) infection pattern changing in a cervical carcinoma prevalent developing country? A retrospective PCR-based study. Poster presentation at the Annual Meeting of USCAP 2017. San Antonio, Texas, USA
  19. Green J, Berrington de Gonzalez A, Sweetland S, Beral V, Chilvers C, Crossley B et al. Risk factors for adenocarcinoma and squamous cell carcinoma of the cervix in women aged 20-44 years: the UK National case-control study of cervical cancer. Br J Cancer 2003;89:2078-2086.
  20. Berrington de Gonzalez A, Seetland S and Green J. Comparison of risk factors for squamous cell and adenocarcinomas of the cervix: a meta-analysis. Br J Cancer 2004;90:1787-1791.
  21. Altekruse SF, Lacey JV, Brinton LA, Gravitt PE, Silverberg SG et al. Comparison of human papillomavirus genotypes, sexual, and reproductive risk factors of cervical adenocarcinoma and squamous cell carcinoma: Northeastern United States. Am J Obstet Gynecol 2003;188:657-63.
  22. Lacey JV Jr, Brinton LA, Abbas FM, Barnes WA, Gravitt PE, Greenberg MD et al. Oral contraceptives as risk factors for cervical adenocarcinomas and squamous cell carcinomas. Cancer Epidemiol Biomarkers Prev 1999;8:1079-85.

 

 

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Cytological Findings of Testicular Fine Needle Aspiration of Azoospermic Men


Cytological Findings of Testicular Fine Needle Aspiration of Azoospermic Men

 *Alam MA,1 Islam MS,2 Hossain N3

 The technique of fine needle aspiration (FNA) has a role as a reliable, quick and easy method of obtaining testicular cells. Recent advances in the management of male infertility or sub fertility and in particular, the finding that spermatozoa recovered from epididymis and testis can result in embryo generation after intracytoplasmic sperm injection (ICSI), question the traditional role of open testicular biopsy for the assessment of spermatogenesis. The purpose of this article was to find out the role of testicular fine needle aspiration cytology in male infertility and to provide brief information on method of needle aspiration, interpretation of testicular fine needle aspiration cytology for evaluation of spermatogenesis, its advantages, limitations and complications as compared to testicular biopsy. Adequate sample were obtained from 62 (84.93%) cases, while 11 (15.06%) cases had inadequate smears where cytological examination could not be possible. The adequate smears were categorized as maturation arrest in 25 (40.32%) cases, sertoli cell only in 21(33.87%) cases, normal spermatogenesis in 10 (16.12%) cases and hypospermatogesis in 6 (9.67%) cases. Testicular FNAC is a significant laboratory technique for the investigation of selected cases of male infertility. Compared to open biopsy, FNA has a number of advantages. Infertile male with severe spermatogenesis disorders can give birth to their own children, whereas only a few years ago the same group of men had only to choose between sperm donation and adoption.

[Journal of Histopathology and Cytopathology, 2018 Jan; 2 (1):51-55]

Key words: Cytology, Fine needle aspiration, testis, azoospermia

  1. *Dr. Md. Ashraful Alam, Associate Professor, Department of Pathology, Rangpur Medical College. drashraful09@gmail.com
  2. Md. Shahidul Islam, Associate Professor, Department of Urology, Rangpur Medical College, Rangpur.
  3. Nusrat Hossain, Junior Consultant, Gynaecology and Obestritics.Palashbari Health Complex, Gaibandha.

 *For correspondence

Introduction

Fine needle aspiration cytology (FNAC) of superficial as well as of deep seated lesions today is a well recognized diagnostic procedure for the diagnosis of neoplastic as well as non-neoplastic and inflammatory lesions. Recently, it has gained popularity for its diagnostic and therapeutic role in male infertility. Since times immemorial the wife has always been blamed for infertility especially in third world countries. Failure to find sperms in post coital test, conducted by Max Huhner in 1913, raised the possibility that husband could be responsible for infertility or sub-fertility. Approximately, 20% cases of infertility are caused entirely by male factor with additional approximately, 30% to 50% of infertile couples.1,2 Azoospermia or absent sperm in semen occurs in approximately, 5% to 10% of infertile men who are evaluated.2 Azoospermia may be obstructive azoospermia (OA) or non-obstructive azoospermia (NOA). The obstructive may have no significant effect on spermatogenesis and may be amenable to surgery, whereas, before introduction of intracytoplasmic sperm injection (ICSI), the only available option for men with NOA was adoption or sperm donor. Assessment of spermatogenesis is an important component in the diagnostic algorithm of male infertility. Traditionally, the testis biopsy has been the gold standard in this evaluation because it provides information in cases of both suspected obstruction and in failing on obstructed testes. Any technique to assess spermatogenesis must be minimally invasive and must conserve as much testicular tissue as possible. It should  not only provide qualitative but also quantitative information about spermatogenesis. In addition to answering the question whether sperm production is normal, it must also address whether sperms are present at all within the testis, as with advances in field of reproductive medicine, even a single sperm can now give men with NOA chance to enjoy biological fatherhood.3 FNAC of the testis is a simple, quick, minimally invasive and painless procedure. The sample can be obtained in outpatient department, can be more representative than biopsy as several separate punctures can be made in one sitting, and there is no local severe pain, haematoma or scarring.

The purpose of this study was to find out the role of testicular fine needle aspiration cytology in male infertility and to provide brief information on method of needle aspiration, interpretation of testicular fine needle aspiration cytology for evaluation of spermatogenesis, its advantages, limitations and complications as compared to testicular biopsy.

Methods

This is an observational study. Fine needle aspiration was performed in 73 azoospermic persons from January 2016 to June 2017 in a private diagnostic laboratory of Rangpur city, Bangladesh. Detailed history and physical examination was performed on all azoospermic people. In addition, semen analysis report was evaluated to confirm azoospermia. Hormonal evaluation including testosterone and FSH levels were obtained in the majority of cases.

FNA Technique

Testicular FNA was done under local anesthesia. The scrotal skin was cleaned by spirit and cotton and bilateral spermatic cord block was achieved by giving 5 to 7 ml of 2%  lignocaine. To quicken the distribution of anesthetic, spermatic cord was gently massaged after injection. After several minutes the testis was firmly palpated to ensure absence of pain. Then the testis was positioned with epididymis and vas deferens directed posteriorly, safe from injury. The scrotal skin was stretched taut over the testes by wrapping the scrotal skin behind the testes with a sponge. Testes was aspirated at three different sites, upper, middle and lower part, using 23 G needle with 10  ml disposable syringe attached to it. Precise gentle in and out movement, varying from 5-8 mm were used. After aspiration, the persons were advised for rest for at least ten minutes. Aspiration was done from both testes for evaluation of spermatogenesis. Slides were prepared from the aspirated material and fixed in 95% alcohol and stained with Papanicolaou (Pap) stain.

Contraindication for bilateral testicular sampling included the presence of local skin infection, hydrocele, orchialgia or previous biopsy.

 FNA Interpretation

All stained FNA cytological smear was interpreted for:

  1. The presence or absence of mature spermatozoa with tails.
  2. Specimen adequacy, as previously reported, an adequate, and informative, FNA specimen was defined as one that contained at least 100 clusters of 20 or more cells or at least 2000 well-dispersed testicular cells.4

 Results

FNA was performed in 73 cases of azoospermic men. The mean age of these men was 32.5 years with a range from 22 to 50 years with period of infertility more than one year. The testicular aspirates were adequate for opinion in 62 cases (Table I) out of 73 cases. The cytological diagnoses in aspirate from 73 cases are depicted in (Table II).

Table I: Adequacy of testicular smears

 

Type of sample No of smears %
Adequate 62 84.93%
Inadequate 11 15.06%

Adequate smears were categorized on cytological examination into Table II:

  1. Normal spermatogenesis in 10 (16.12%) cases.
  2. Sertoli cell only in 21 (33.87%) cases.
  3. Hypo spermatogenesis in 6 (9.67%) cases.
  4. Maturation arrest in 25(40.32%) cases.

Normal spermatogenesis of testes on FNA revealed all germ cell maturation steps from spearmatogonia till mature spermatozoa.

Maturation arrest category shows no spermatozoa, with presence of immature germ cells, including primary spermatocytes and spermatids.

Sertoli cells only on FNA of testes showing only sertoli cell.

Spermatogonia were seen as large cells with round nuclei and finely granular chromatin with a thin rim of cytoplasm 5

During our study 2 (2.73%) person complained severe pain. No one complained prolong pain or any haematoma formation.

Table II: Cytological diagnosis of 73 cases

 

Cytological diagnosis No. of cases (%)
Normal spermatogenesis 10(16.12%)
Sertoli cell only 21(33.87%)
Hypo spermatogenesis 6(9.67%)
Maturation arrest 25(40.32%)

 

 

 

 

 

 

Figure 1. Photomicrograph showing sertoli cell only (x400)

 

 

 

 

 

 

Figure 2. Photomicrograph showing hypo- spermatogenesis (x400)

Discussion

Posner and Huhner first used testicular puncture biopsies in the investigation of human infertility that examined unstained samples for spermatozoa.6  Later fine needle aspiration of the testis pioneered by Obrant and Persson (1965) was proposed as a non invasive technique.6 Characterizing the cell types was straightforward, with not much difficulty in recognizing germ cells and sertoli cells were adequate. The materials aspirated by FNAC were adequate in majority of cases (84.93%). The adequacy rate has similarity with the findings of  Ahmed.7 In our study, normal spermatogenesis was found by testicular FNAC in 16.12% of cases of azoosperic men. This finding, however, differed from the findings observed in a study done by Kuerin A et al.8 This may be  due to small number of cases in our study. In our study maturation arrest and sertoli cell only found in 40.32% and 33.87% cases respectively which were similar to the findings found by Ahmed. In our study we found 9.67% cases of hypospermatogenesis which are similar to the findings of Ahamad SU et al9 and RC Adhikari findings.10

In the present study we have done multiple aspirations of both testes under local anaesthetia by cord blocking. Some author performed aspiration by giving per rectal diclofenac sodium suppository.

Most of the authors have performed FNA under general anaesthetia or local anaesthetia. Verma A K et al performed FNA without general or local anaesthetia and found the technique is well tolerated by the most patients.11  Single aspirate may not be truly representative.12 However some studies have described sampling in one testis.10,13 The study used sampling of both testes and findings were also different in both testes. Adhikari RC observed severe pain after FNA procedure in 31.68% cases and haematoma in 2.97% person. Which was completely different observation from our observation. Rajawanshi et al.14,15 observed only complication was prolonged pain in some patients. In our study we noted only 2.73% persons complained prolong pain but no haematoma formation, that are similar observation with Ahamad MSU et al.

 Conclusion

Testicular FNAC is a significant laboratory technique for the investigation of selected cases of male infertility. Compared to open biopsy, FNA has a number of advantages;  therefore, it is already used as a diagnostic and therapeutic method in some andrology centers. FNA combined with the introduction of ICSI (intracytoplasmic sperm injection) have revolutionized the management of male infertility in the  recent years. Infertile male with severe spermatogenesis disorders can have their own children, whereas only a few years ago the same group of men had only to choose between sperm donation and adoption.

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