Nasir Ud Din

Secretory carcinoma of breast: clinicopathologic study of 8 cases

Our aim was to describe clinicopathologic features of secretory carcinoma on a cohort of cases. We retrieved reported cases of secretory carcinoma of breast (SCB) in the Section of Histopathology, Department of Pathology & Microbiology, Aga Khan University Hospital Karachi, from May 2004 to December 2011. The slides were reviewed, and clinicopathologic features were noted. A total of 8 cases of SCB were found. The age ranged from 17 to 60 years (median, 41 years) with a female to male ratio of 7:1. Lumpectomy was done in 6 cases, and mastectomy, in 2 cases. The tumor size ranged from 2.5 to 10 cm (mean, 5.5 cm). Histologically, abundant extra- and intracellular secretory material was seen in all cases. Most of the tumors showed mixtures of patterns with dominant microcystic and papillary patterns. In situ component was seen in only 1 case. Lymph node metastases were seen in both cases with lymph node sampling. In conclusion, SCB is a rare type of ductal breast carcinoma. The papillary pattern of SCB is rare according to published data but was seen in most of our cases. In situ secretory carcinoma is even rarer, and to date, we have seen a single case only. Although most occur in women, these can be seen in men as well.

Gastrointestinal, liver and biliary tract pathology: a histopathological and epidemiological perspective from Pakistan with a review of the literature.

AIMnTo present an epidemiological and histological perspective of diseases of the gastrointestinal tract (including liver and biliary tract) at the Section of Histopathology, Department of Pathology, AKUH, Karachi, Pakistan.nnnMATERIALS AND METHODSnAll consecutive endoscopic biopsies and resections between October 1 and December 31, 2012 were included.nnnRESULTSnA total of 2,323 cases were included. Carcinoma was overwhelmingly the commonest diagnosis on esophageal biopsies (69.1%); chronic helicobacter gastritis (45.6%) followed by adenocarcinoma (23.5%) were the commonest diagnoses on gastric biopsies; adenocarcinoma (27.3%) followed by ulcerative colitis (13.1%) were the commonest diagnoses on colonic biopsies; acute appendicitis (59.1%) was the commonest diagnosis on appendicectomy specimens; chronic viral hepatitis (44.8%) followed by hepatocellular carcinoma (23.4%) were the commonest diagnoses on liver biopsies; chronic cholecystitis was the commonest diagnosis (over 89%) on cholecystectomy specimens.nnnCONCLUSIONSnSquamous cell carcinoma comprised 88.8% of esophageal cancers. About 67% were in the lower third and 56.5% were moderately differentiated; mean ages 49.8 years for females and 55.8 years for males; 66% cases were from South West Pakistan. Over 67% patients with gastric adenocarcinoma were males; mean ages 59 and 44 years in males and females respectively, about 74% gastric carcinomas were poorly differentiated; and 62.2% were located in the antropyloric region. About 63% patients with colorectal adenocarcinoma were males; mean ages 46.1 and 50.5 years for males and females respectively; tumor grade was moderately differentiated in 54%; over 80% were located in the left colon. In 21.2% appendicectomies, no acute inflammation was found. Acute appendicitis was most common in young people. Hepatitis C (66.3%) was more common than hepatitis B (33.7%); about 78% cases of hepatocellular carcinoma occurred in males; females comprised 76.7% patients with chronic cholecystitis; and 77.8% patients with gall bladder carcinoma. All resection specimens showed advanced cancers. Most cancers occurred after the age of 50 years.

Central, Extraventricular and Atypical Neurocytomas: a Clinicopathologic Study of 35 Cases from Pakistan Plus a Detailed Review of the Published Literature

BACKGROUNDnCentral neurocytomas are rare neuronal neoplasms with a favorable prognosis. They are typically located in the lateral ventricles of the brain and mostly histologically correspond to WHO grade II with a Mib 1 labelling index of <2%. Similar tumors located in the cerebral hemispheres and spinal cord, for example, are called extraventricular neurocytomas. A few tumors histologically show atypia, mitoses, vascular proliferation and/or necrosis and a Mib 1 index >2 % and are designated as atypical neurocytomas.nnnAIMnThe aim of our study was to describe the common as well as unusual morphologic features and the role of various immunohistochemical stains in the diagnosis of these rare tumors.nnnMATERIALS AND METHODSnWe retrieved and reviewed 35 cases diagnosed between 2001 and 2015.nnnRESULTSnSixty percent of patients were males, and the mean age was 26 years. 31 cases (88.6%) were intraventricular and 4(11.4%) were extraventricular. Histologically, 6 cases (17.1%) were compatible with atypical neurocytomas. All cases showed the classic morphology comprising nests and sheets of uniform, round cells with uniform round to oval nuclei with finely speckled chromatin and perinuclear cytoplasmic clearing (halos). All cases also showed delicate, fibrillary, neuropil-like matrices. Other common histologic features included capillary-sized blood vessels in a branching pattern in 57.1%, foci of calcification in 34.3% and perivascular pseudorosettes in 20%. Rare findings included Homer- Wright or true rosettes in 8.6% and ganglioid cells in 2.9%. Synaptophysin was the most consistent and valuable marker, being positive in almost all cases. GFAP positivity in tumor cells was seen in 25.7% of cases. Follow up was available in 13 patients. Of these 9 had histologically typical and 4 had atypical tumors. Only 1 (with an atypical neurocytoma) died, probably due to complications of surgery within one month, while 12 (including 3 with atypical neurocytomas) remained alive. Recurrence developed in 1 of these 12 patients (histologically consistent with typical morphology) almost 9 years after surgery. Only 4 patients, including 2 with atypical tumors, received postoperative radiotherapy, all with surgery in 2010 or later. Overall, prognosis was excellent with prolonged, recurrence free survival and most patients, even without receiving radiation therapy, were alive and well for many years, even a decade or more after surgery, without developing any recurrence, indicating the benign nature of these neoplasms.

Gastrointestinal Stromal Tumors: A Clinicopathologic and Risk Stratification Study of 255 Cases from Pakistan and Review of Literature

PURPOSEnTo describe the clinicopathological features of gastrointestinal stromal tumors (GIST) diagnosed in our section and to perform risk stratification of our cases by assigning them to specific risk categories and groups for disease progression based on proposals by Fletcher et al and Miettinen and Lasota.nnnMATERIALS AND RESULTSnWe retrieved 255 cases of GIST diagnosed between 2003 and 2014. Over 59% were male. The age range was 16 to 83 years with a mean of 51 years. Over 70% occurred between 40 and 70 years of age. Average diameter of tumors was 10 cms. The stomach was the most common site accounting for about 40%. EGISTs constituted about 16%. On histologic examination, spindle cell morphology was seen in almost of 85% cases. CD117 was the most useful immunohistochemical antibody, positive in 98%. Risk stratification was possible for 220 cases. Based on Fletchers consensus proposal, 62.3 gastric, 81.8% duodenal, 68% small intestinal, 72% colorectal and 89% EGISTs were assigned to the high risk category; while based on Miettinen and Lasotas algorithm, about 48% gastric, 100% duodenal, 76% small intestinal, 100% colorectal and 100% EGISTs in our study were associated with high risk for disease progression, tumor metastasis and tumor related death. Follow up was available in 95 patients; 26 were dead and 69 alive at follow up. Most of the patients who died had high risk disease and on average death occurred just a few months to a maximum of one to two years after initial surgical resection.nnnCONCLUSIONSnEpidemiological and morphologic findings in our study were similar to international published data. The majority of cases in our study belonged to the high risk category.

Epidemiologic Data, Tumor Size, Histologic Tumor Type and Grade, Pathologic Staging and Follow Up in Cancers of the Ampullary Region and Head of Pancreas in 311 Whipple Resection Specimens of Pakistani Patients.

AIMnTo report the histologic findings on Whipple resection specimens and thus determine the extent and spread of carcinomas of ampullary region and head of pancreas in our population.nnnSETTINGnSection of Histopathology, Department of Pathology, Aga Khan University Hospital (AKUH), Karachi, Pakistan.nnnMATERIALS AND METHODSnA case series of 311 consecutive Whipple resection specimens received between January 1,2003 and December 31, 2014. Specimens processed for histologic sections and representative sections submitted and histologically examined as per established and standard protocols. All relevant tumor parameters including histologic type, histologic grade, pathologic T and N stage and tumor size were assessed. Epidemiologic data were also recorded. All findings were analysed using SPSS 19.0 software.nnnRESULTSnAmpullary (periampullary) carcinomas were much more common than carcinomas of the head of the pancreas, especially in males, with an average age of 53 years. Mean tumor size was 2.5 cms, over 54% were well differentiated. A large majority were pT2 or pT3 and N0. Carcinomas of pancreatic head were also more common in males, mean age was 55 years, mean tumor size was 3.5 cms, and over 65% were moderately differentiated. The majority were T2 or T3 and pN1. Prognostically, significant statistical correlation was seen with tumor grade and pathologic T and N stage (p values statistically significant). However, tumor size was not statistically significant.nnnCONCLUSIONSnAmpullary carcinomas are more common compared to pancreatic carcinomas. Majority of ampullary carcinomas were well differentiated while majority of pancreatic carcinomas were moderately differentiated. Large majority of both types of cases were pT2 or T3. Histologic tumor grade and pathologic T and N stage are significantly related to prognosis in Pakistani patients with ampullary and pancreatic cancers.

Rhabdomyosarcoma - an Epidemiological and Histopathologic Study of 277 Cases from a Major Tertiary Care Center in Karachi, Pakistan

AIMnTo present the epidemiologic data (age, gender, size etc) and histopathologic and immunohistochemical features of cases of rhabdomyosarcoma (RMS) reported in our department.nnnSETTINGSnSection of Histopathology, Department of Pathology and Microbiology, Aga Khan University Hospital, Karachi, Pakistan.nnnDURATIONnAll cases of RMS diagnosed between January 1, 2003 and December 31, 2012 were included in the study.nnnRESULTSnA total of 277 cases were included. Embryonal rhabdomyosarcoma (ERMS) was by far the dominant histologic type (87.4%) followed by alveolar type (ARMS)(9.4%). ERMS was much more common in males (64.0%)and over 65% of cases occurred in the first decade of life (over 90% in the first two decades). Head and neck region was commonest site for ERMS (46.7%), followed by the genitourinary system (16.1%). Over 65% cases of ARMS occurred in the extremities. Over 80% cases of ARMS occurred in the first 3 decades of life. Immunohistochemical staining for Desmin and MyoD1 was positive in 96.7% and 85.4% respectively.nnnCONCLUSIONSnThe epidemiologic data and microscopic findings in our patients are similar to international published data on rhabdomyosarcoma.

Synchronous and Metachronous Malignant Epithelial and Lymphoid Tumors: a Clinicopathologic Study of 10 Patients from a Major Tertiary Care Center in Pakistan

Case reports and case series documenting unfortunate patients with more than one malignant neoplasm are rare but well established. While majority of such patients have two malignancies, cases with three or even four malignant neoplasms in the same patient have been published in literature. A number of factors influencing carcinogenesis have been implicated in such cases including exposure to large amounts of radiation, chemotherapy for the original malignancy; prolonged history of heavy smoking and exposure to other environmental carcinogens; aging; and underlying genetic alterations. Concomitant multiple malignant neoplasms may be synchronous-two or more malignant neoplasms histologically distinct from each other, arising in the same site and detected simultaneously (for example during the same hospital admission) or detected one after the other in sequence in a period less than 6 months; or metachronous-two or more malignant neoplasms of similar or distinct histologic type detected at different times (after an interval of greater than 6 months) in different anatomic sites. Any combination of malignant tumors can occur in the same patient for example carcinomas with other carcinomas, carcinomas with Non-Hodgkin or Hodgkin lymphomas, carcinomas with mesotheliomas, carcinomas with sarcomas etc. We have reported several cases with multiple malignancies during our practice, and these cases were composed of the different combinations described above. The aim of the present study is to document 10 such cases of combined carcinoma and Non Hodgkin lymphoma in the same patient which were diagnosed in our section.

Malignant phyllodes tumor in an 11-year-old girl with fatal clinical outcome. A case report

BACKGROUNDnPhyllodes tumors are rare biphasic tumors occur predominantly in middle aged women. Malignant phyllodes tumor in children is very rare.nnnOBJECTIVEnTo report a case of malignant phyllodes tumor in a pre-menarchal girl.nnnMETHODSnH&E slides of the case were reviewed and follow up was obtained.nnnRESULTSnThe patient was 11-year-old girl who noticed a lump in her right breast 1 year back which grew rapidly in size. Wide local excision of the mass was done and histopathology revealed a malignant phyllodes tumor. Patient underwent mastectomy one month later due to recurrence. Two years later, she presented with dyspnea and chest pain. CT showed lung metastasis. The patient died of disease 1 year later due to widespread metastasis in liver and bone.nnnCONCLUSIONnWe report a case of malignant phyllodes tumor in an 11-year-old girl, which behaved aggressively and patient died of disease due to widespread metastases 3 years after diagnosis.

Mammary myofibroblastoma: a clinico- pathologic study of six cases.

BACKGROUNDnMammary myofibroblastoma is a rare and benign neoplasm of the breast stroma, showing features of fibroblasts and myofibroblasts. It has also been noted to exhibit smooth muscle cell characteristics.nnnOBJECTIVEnThe aim of this study was to describe the clinical and pathological features of mammary myofibroblastoma reported at our institution.nnnMETHODSnCases of mammary myofibroblastoma reported in our laboratory were retrieved by electronic search. H&E slides were reviewed and clinico-pathologic features were noted. Immunohistochemistery was performed by Envision method. Only CD34 and CKAE1/AE3 were performed in all 6 cases. ASMA, desmin and S-100 were performed in 5, 4 and 2 cases, respectively. Vimentin and Bcl-2 were performed in one case.nnnRESULTSnA total of 6 cases were identified. Five were female and one was male. The mean age of patients was 45.5 years. The mean size of tumors was 7.7 cm in the largest dimension. Histologically, four cases showed clusters of uniform bipolar spindle shaped cells separated by broad bands of hyalinized collagen. Mitotic figures ranged from none to 3 mitoses/10 HPFs. One case showed combined features of cellular and fibrous areas. Another case was epithelioid-cell type. On immunohistochemistry, CD34 stain was positive in 5/6 cases, ASMA in 3/5 cases, desmin in 2/4 cases, S-100 in none and vimentin and Bcl-2 in 1/6 cases. None of the cases stained positive for CKAE1/AE3.nnnCONCLUSIONSnDue to the varying degree of fibro-myofibroblastic differentiation, myofibroblastoma shows multiple morphologies and several intratumoral and intertumoral types. It is essential to distinguish each variant from the other to avoid inaccurate diagnosis of other benign or malignant breast conditions, becoming a noteworthy diagnostic dilemma for histopathologists.

Atypical Teratoid/ Rhabdoid Tumor of Brain: a Clinicopathologic Study of Eleven Patients and Review of Literature

Background: Atypical teratoid/ rhabdoid tumor (AT/RT) is a rare aggressive embryonal central nervous system (CNS) tumor of infancy and early childhood. Majority of the cases arise in the posterior fossa, and remaining in the cerebrum. Aims: To analyze the clinicopathologic features of AT/RT on a cohort of cases. Materials and methods: All reported cases of AT/RT at the Department of Pathology and Laboratory Medicine, Aga Khan University Hospital (AKUH) from 2007 to 2016 were reviewed for clinical and pathological features. Immunohistochemical stain for INI-1 was performed in all 11 cases. Follow up was obtained. Results: A total of 11 cases were identified. Seven patients were males and 4 were females. The ages ranged from 1 month to 48 months (mean 26.6 months). Six tumors were located in the cerebrum and 3 in the posterior fossa. Exact Location was not known in 2 cases. Histologically, rhabdoid cells were present in sheets in variable proportions in five cases, Medulloblastoma and PNET like areas were seen in 2 cases each. Immunohistochemical stains EMA (10/10), vimentin (7/7), CKAE1/AE3 (8/9), and CD99 (3/4), GFAP (6/10), ASMA (3/4) and synaptophysin (3/4) were positive in varying proportions while desmin was negative in all 6 cases in which it was performed. All 11 tumors lacked immunoreactivity for INI-1 protein. Four patients died of disease with a follow up ranging from 5 to 24 months. Conclusions: AT/RT is a rare highly aggressive embryonal tumor of CNS. A male predominance was noted in our series. We report the first and largest series from Pakistan.