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INTRODUCTION Fine needle aspiration cytology (FNAC), along with thyroid ultrasound, is an important tool in evaluation of thyroid nodules that helps in further management of these patients in making a decision of surgical intervention vs follow-up. The Bethesda System for Reporting Thyroid Cytopathology category III of atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS) has risk of malignancy (ROM) ranging from 5% to 15%. The aim of the present study was to describe the frequency of AUS/FLUS in thyroid gland FNACs and the surgical outcomes of these cases. METHODS The integrated laboratory management system retrieved the thyroid FNACs from 2010 to 2018 and subsequent surgical pathology specimens. For the AUS/FLUS cases, data regarding patient demographics, cytology and histological diagnoses were recorded. The results were tabulated as the overall frequency of AUS/FLUS in thyroid FNACs, cytohistological correlation (benign and malignant) and ROM. RESULTS Over a period of 9 years, 256 (10.9%) cases out of 2342 thyroid FNACs were reported as AUS/FLUS at our institution. Mean age was 43.5 years. The majority (70.3%) of patients were female. Seventy-two of 104 resection specimens (69.2%) were reported as benign and 32 cases (30.7%) had malignant diagnosis. Upper-bound ROM was 30.7% (32 cases with malignant diagnosis out of 104 resection specimens). Lower-bound ROM was calculated as 12.5% (32 cases with malignant diagnosis out of 256 total AUS diagnosis). CONCLUSION The AUS/FLUS category of thyroid cytology and associated ROM remain an evolving area. Individual institutions should monitor the frequency and include ROM in the dashboard indicators to remain within the recommended range.

Spermatocytic tumor is a rare germ cell tumor not related to germ cell neoplasia in situ, and derived from postpubertal-type germ cells. It was previously called "Spermatocytic Seminoma" due to false belief of its origin from germ cell neoplasia in situ. The tumor usually occurs in an older age group and orchidectomy is curative. We present a case of spermatocytic tumor in a 25-year male who presented with right-sided testicular swelling and right-sided varicocele. Radiology revealed a 9.8 × 9 cm testicular mass and the patient underwent right-sided orchidectomy. Microscopic examination showed classic morphology with three characteristic cell types and diagnosis of spermatocytic tumor was made. Key Words: Spermatocytic tumor, testis, young.

The history of glomangiopericytoma began in 1924 when it was initially diagnosed by Stout and Murray. It is a rare tumour of the respiratory mucosa, with a prevalence of less than 0.5% among all sinonasal tumours. Literature shows female predominance among patients who develop glomangiopericytoma. So far, no accurate aetiology has been discovered, but there are certain risk factors, including trauma, use of corticosteroids and high blood pressure, which are believed to cause glomangiopericytoma. Patients usually present with a history of epistaxis or nasal blockage, though symptoms can get worse if the tumour is not resected timely and can lead to visual disturbance, chronic sinusitis and headache. It has reddish polypoidal appearance on examination. The best modality for the treatment of glomangiopericytoma is endoscopic surgical resection via trans-nasal approach. We present the case of a 70-year-old man, with nasal blockage and epistaxis who underwent endoscopic sinus surgery for this condition.

A wide variety of diseases and drugs can cause cutaneous pustular eruptions. Acute generalized exanthematous pustulosis (AGEP) is a unique drug-induced dermatosis clinically presented as erythematous papular and pustular eruption, usually caused by certain systemic drugs. We are presenting a very rare association of AGEP with a biological agent, cetuximab. A male aged 66 years, who was recently diagnosed with a case of squamous cell carcinoma of glottis, presented in the dermatology clinic with a recent onset of fever and widespread pustular eruption over the face, trunk, and limbs. The eruption was noted after the injection of cetuximab given for his squamous cell carcinoma. The clinical history, typical physical findings, and histopathological features confirm the diagnosis of AGEP. The injection cetuximab was stopped and the patient was treated with some topical and systemic medications and the symptoms resolved completely in a few weeks. Our case is an interesting clinical presentation of AGEP due to cetuximab therapy and confirms that this is an extremely rare and proven adverse effect of cetuximab. To our knowledge, this is the first-ever reported case of AGEP associated with cetuximab. Physicians need to be aware of this unique but important side effect of cetuximab and perform a proper physical examination and specific investigations that can be useful to reach a final diagnosis.

Background The most common endocrine tumor is thyroid cancer. Follicular thyroid carcinoma (FTC) accounts for 5-10% of all thyroid cancers. Patients with FTC frequently present with more advanced diseases and a higher occurrence of distant metastases because of the propensity of vascular invasion. FTC is mainly treated with surgery while radioactive iodine (RAI) therapy is the main adjuvant therapy according to the American Thyroid Association guidelines. Methodology This was a retrospective observational study of FTC patients aged 18 and above conducted at a tertiary care hospital in Karachi from January 01, 2010 to December 31, 2019. Results A total of 404 patients with thyroid carcinoma were sorted, of which 40 (10.1%) were FTC cases. Overall, 50% of the patients were in the age group of 41-60 years, and the female-to-male ratio was 1.5:1. The majority of patients (60%) presented with neck swelling, followed by bone and lung metastasis in 20% and compressive symptoms in another 20%. On fine needle aspiration cytology (FNAC), 50% had Bethesda category III-IV nodules while 10% had Bethesda category II. Overall, 50% had a total thyroidectomy while 50% had a lobectomy followed by a completion thyroidectomy. On histopathology, 23 (57.5%) patients had minimally invasive FTC while 17 (42.5%) had widely invasive FTC. A total of 17 (42.5%) patients had received RAI 30-100 mCi while 10 (25%) received more than 100 mCi. Conclusions FTC can present with both local or metastatic symptoms. The atypical presentation of metastatic FTC should be considered, diagnosed, and managed early to limit mortality and morbidity. Ultrasound is the best diagnostic investigation of choice followed by FNAC. Surgery is the mainstay of treatment and should be followed by RAI in select cases. Thus, understanding the trend of FTC and proper planning and utilization of the resources will help developing countries in effectively treating the FTC.

Background Neo-adjuvant chemotherapy (NAC) is frequently administered in breast carcinoma patients. The clinical response to NAC guides further treatment. The pathological response is not only an independent prognostic factor, but it also guides further treatment and prognosis. Objectives The aim of our study was to find the degree of concordance between clinical and pathological response assessments after NAC in Invasive lobular Carcinoma (ILC) cases by using World Health Organization (WHO) criteria and different pathological systems, respectively. We also tried to identify any useful parameter of clinical assessment that could better correlate with pathologic assessment and provide a better estimation of residual tumor. Methods This retrospective study was conducted on 26 ILC tumors diagnosed in 24 patients who were treated with NAC followed by surgical resection between January 2009 and December 2020. Medical records and microscopy glass slides were reviewed for clinical and pathological response assessments, respectively. Results The pre-treatment tumor area ranged from 1.8-255 cm2 and the mean±SD was 52.2±66.8 cm2. After NAC, complete clinical response was observed in four (15.3%) cases. The clinically assessed mean tumor area significantly reduced from 52.2±66.8 cm2 to 17.2±22.6 cm2 (p-value

Malignant eccrine spiradenoma (MES) is an exceedingly rare skin adnexal tumor that arises from pre-existing benign eccrine spiradenoma (BES). MES tumors show a wide spectrum of morphological features, posing a diagnostic challenge to the pathologist. Sarcomatous (heterologous) elements are seen in a few of these tumors, further complicating the morphological picture. We herein describe a case of a 66-year-old male who presented with a recently enlarging, ulcerated, nodular skin lesion over the right leg that had been present for the last 25 years. The patient underwent wide local excision of the tumor. Microscopic examination revealed a neoplastic lesion comprising benign and malignant components. The carcinomatous component showed features of infiltrating adenocarcinoma, not otherwise specified, whereas the sarcomatous component showed predominant osteosarcomatous and focal chondrosarcomatous differentiation. The benign component showed morphological and immunohistochemical features of BES. No adjuvant treatment was administered. The patient was alive and disease-free for 14 months, after which he was lost to follow-up. Careful identification and knowledge related to histological diversity are keys to the correct diagnosis of this rare tumor. MESs are potentially aggressive tumors, and therefore, close long-term follow-up should be maintained.

Erythema annulare centrifugum (EAC) is an unusual skin condition appearing as recurrent erythematous annular eruptions associated with autoimmune disorders, infections, and various neoplastic conditions. We present a very rarely reported association of EAC with Hashimoto thyroiditis (HT) in a young male. A 26-year-old male recently diagnosed as case of HT presented in the dermatology clinic with nine-month history of non-itchy persistent annular lesions on the body. The morphology and biopsy of lesions confirmed the diagnosis of EAC. HT is a part of the spectrum of autoimmune thyroid diseases with its own specific cutaneous manifestations. Our case also depicts the impact of antigen-antibody related immunological reaction, which might be involved in the development of both HT and EAC, and it could be the stages of the same pathological condition of two different clinical presentations.

Background The 2014 WHO Classification of ovarian neoplasms introduced a new entity of seromucinous tumors associated with endometriosis. These tumors encompassed a spectrum from benign to malignant and included seromucinous cystadenoma/ cystadenofibroma, seromucinous borderline tumor/atypical proliferative seromucinous tumor and seromucinous carcinoma. However, the 2020 WHO Classification of Female Genital Tumours removed seromucinous carcinomas as a distinct entity and recategorized them as Endometrioid carcinomas with mucinous differentiation. Here we describe clinico-morphologic features of seromucinous tumors recategorizing cases originally diagnosed as seromucinous carcinoma in light of 2020 WHO classification and present detailed review of literature. Methods Slides of seromucinous tumors were reviewed. Special emphasis was given to evaluation of stromal invasion. Follow-up was obtained. Results Ten cases were diagnosed. Mean age was 40 years. Four cases were bilateral. Mean size was 19 cm. Grossly; luminal papillary projections were seen in 6 cases. Tumors demonstrated a papillary architecture with papillae lined by stratified seromucinous epithelium showing nuclear atypia. Stromal invasion was seen in 4 cases. Six cases were reported as borderline seromucinous tumors and 4 cases originally diagnosed as seromucinous carcinoma were recategorized as endometrioid carcinoma with mucinous differentiation on review. Endometriosis was seen in 4 cases. CK7, PAX8 and ER were positive in 7/7 cases. Two cases showed extra-ovarian involvement. Follow up was available in 7 cases. Six patients were alive and well at follow up ranging from 8 to 46 months. Six patients received chemotherapy postoperatively. One patient with carcinoma died of disease 18 months postoperatively. Conclusion In our series, 4 cases were originally diagnosed as seromucinous carcinomas. However, these were recategorized in light of the 2020 WHO Classification of Female Genital tumors as endometrioid carcinomas with mucinous differentiation. Six cases were diagnosed as seromucinous borderline tumors. Thus, majority of cases were borderline in agreement with published literature.

Endocrine pathology primarily includes non-neoplastic and neoplastic lesions of ‘thyroid’, ‘parathyroid’, ‘pituitary’, ‘adrenal’ and ‘pancreatic’ biopsies, thyroid being the most common. Disease spectrum ranges from ‘inflammatory’ to more common ‘neoplastic’ disorders. Thyroid neoplasms, in particular various types of thyroid carcinomas, are among the most frequently encountered biopsies. One particular area of difficulty and controversy includes ‘follicular neoplasms’ of thyroid where diagnostic criteria and even diagnostic entities and nomenclature keep on changing every few years. This chapter covers diagnostic light microscopic features with latest criteria as per the most recent WHO guidelines. Ancillary testing like special stains and immunohistochemical stains utility is also incorporated for ready reference.

The skin is the biggest organ of our body; hence limitless diversity of the various types of lesions leaves a general pathologist struggling. This diversity ranges from allergic, inflammatory, bullous to melanocytic and non-melanocytic neoplasms including a wide variety of adnexal tumours. At times distinguishing features are subtle, and not enough clinical presentation and details are provided which are mandatory for critical evaluation of skin biopsies in correct perspective. For the obvious reason, a general pathology atlas cannot do justice with this subject as the subject demands; however an attempt is made to adequately describe diagnostic features of more commonly encountered lesions.

Objective: To determine the cases of Noninvasive Follicular thyroid neoplasm with papillary like nuclear features (NIFTP) in Pakistani population retrospectively. Another objective was to determine their clinical and radiological outcomes with respect to local and systemic disease recurrence, reconfirming the benign course of this new nomenclature in Thyroid tumors by WHO in our population would encourage adopting the new conservative treatment approach in such patients. Methods: This is a retrospective cohort study conducted at a tertiary care center in Karachi, Pakistan from 2007-2016. All follicular Variant papillary thyroid cancer (FVPTC) reported from a single institute had their histopathology slides reexamined for diagnosing NIFTP as per the new WHO criteria. These cases were then followed retrospectively from their diagnosis onset through their medical and electronic health record for any local or systemic disease recurrence. Results: There were 199 cases of Papillary Thyroid cancer (PTC) which included 22 cases of FVPTC. Eleven cases fulfilled NIFTP criteria with tumor size ranging from 1.1cm to ≥ 5.5cm. All patients in the NIFTP group underwent total thyroidectomy. Nine patients (81.81%) received RAI131 therapy. Four (45%) patients had a median follow up of three to four years. There was no disease recurrence seen on both ultrasound and RAI scans of patients in the NIFTP group. Seven patients (87.5%) had normal surveillance thyroglobulin levels except one whereas three patients were lost to follow up. There was no disease recurrence seen both radiologically and biochemically in the NIFTP group. Conclusion: Our study favors the low risk nature of NIFTP with no disease recurrence in the cases studied and encourages de-escalation of treatment. doi: https://doi.org/10.12669/pjms.36.2.1123 How to cite this:Jabeen S, Fatima S, Sheikh A, Islam N. Non Invasive Follicular Thyroid Neoplasm with Papillary like nuclear features (NIFTP): A time for change in Pakistan. Pak J Med Sci. 2020;36(2):151-155. doi: https://doi.org/10.12669/pjms.36.2.1123 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Sclerosing mucoepidermoid carcinoma of the thyroid was first reported in 1991. This tumour type may develop as associated to Hashimoto thyroiditis. There are two variants of mucoepidermoid carcinoma of thyroid. The conventional and the sclerosing variants. Sclerosing mucoepidermoid carcinoma with eosinophilia of thyroid (SCME) has recently been recognised as a separate disease entity by the WHO. We report a case of SCME in a 62-year-old male patient who presented with a painless anterior neck swelling. Total thyroidectomy was performed, and no adjuvant treatment administered. The patient remained disease free up until 10 months of follow-up. Approximately 40 cases are reported in literature. We report the second case of SCME in Asian men. Sclerosing mucoepidermoid carcinoma with eosinophilia of thyroid should be differentiated from the conventional mucoepidermoid carcinoma. Patients should also be advised of long-term follow-up for surveillance.

Stem cells are the small units of multicellular creature. Regeneration and self-renewal are the ability of the stem cells. Each tissue is having particular stem cells, specific to it. These normal stem cells are converted into cancer stem cells through mutations in it. Although the expression of oncogenes is enhanced a lot, the tumor-supressing gene is lessened. Cancer stem cells are isolated and visualized through different techniques like immunocytochemical staining, spectral karyotyping, immunohistochemistry, induction method and dissection measures, then are performed histological procedures which include fascination, immunohistochemistry, dispensation, in situ hybridization and also quantitative examination of tissue flow cytometric analysis. For the analysis of quantization, statistical tests are also performed as two-sample t-test, Chi-square test, SD and arithmetic mean. Tumor cells generate glioma spheres. These are used in cancer study. Axin 1 is the gene suppressing cancer. Its removal causes the generation of liver cancer. Curcumin is the most effective for suppressing cancer as it increases the normal stem cell function and decreases the cancer stem cell function. Brahma-related gene 1 is crucial for the safeguarding of the stem cell residents in tissue-specific comportment. Different types of cancers originate through genetic mutation, tissue disorganization and cell proliferation. Tumor configuration is produced by the alteration in original cell culture having stem cells and progenitor cell populations. The developmental facets about cancer cells and cancer stem cells as well as their personal natal functions sustain an intricate steadiness to settle on their personal donations to the efficacy or harmfulness of the biological organization.

Objectives To present the clinicopathological experience of Olfactory Neuroblastoma (ONB) with emphasis on histopathological and immunohistochemical features. Methods A descriptive cross-sectional study was done on 36 cases of ONB, selected by non-probability purposive sampling. Theses cases of ONB were retrieved and reviewed from surgical pathology database of Aga Khan University Hospital reported between January 1993 and March 2015. Results Tumor size and age of presentation was wide in range without any distinct bimodal distribution. Nasal cavity was most common site along with involvement of paranasal sinuses. More than 50% cases had Kadish stage A. Microscopically, most cases were Grade-1 and majority showed partial or complete lobular architecture. Neurofibrillary matrix was observed in 2/3(rd) of cases. Among immunohistochemical markers, Neuron Specific Enolase was most frequently expressed. Unusual positive expression of Cytokeratin AE1/AE3 and Cytokeratin CAM5.2 was also seen focally in few cases. Conclusion The ONB has great variability of histological and clinical presentation, and immunohistochemical markers are useful to differentiate from more common small round blue cell tumours of nasal cavity.

A 62-year-old man, suffering from bronchial asthma was evaluated due to intractable cough. His dyspnea was controlled but cough remained unresponsive to escalation of asthma management steps. Cough occurred in bouts, especially during night time and was occasionally productive of mucoid sputum. Other than bilateral rhonchi on chest auscultation, remaining systemic examination was unremarkable. CT chest showed a mass lesion in the bronchus intermedius that was confirmed on bronchoscopy and was removed after electrocautery snare excision. Histopathology of the lesion was consistent with endobronchial chondroma. The patient experienced a dramatic resolution of cough post tumor removal. Follow up bronchoscopy after 24 months revealed no tumor recurrence.

Background: Mycosis fungoides (MF) is the most common primary cutaneous lymphoma. It affects usually the covered areas of the body in elderly males in 6th and 7th decades of life. Atypical dermal lymphoid infiltrate is seen along with epidermotropism. Nuclei of neoplastic cells are convoluted. The neoplastic cells demonstrate positivity for CD3 (Pan T) immunohistochemical stain. Majority show increased CD4 to CD8 ratio. The present study was done to study the clinicopathological features, which might be of help in reaching a correct diagnosis in these cases. Materials and Methods: A retrospective descriptive study was conducted on 60 reported cases of MF. The retrieved slides were reviewed for clinical and histopathological features and immunohistochemical profile. Results: The ages ranged from 20–84 years, mean age was 47 years. Majority (75%) of patients were male. Trunk and extremities were the sites most commonly affected. There was significant inverse correlation between epidermal thickness and tumor stage (P = 0.02). Thickened epidermis was seen in patch stage and thickness reduced with progressing stage. The intensity of dermal infiltrate and cell size was also statistically significantly linked to stage progression (P < 0.001 each). In addition, proliferation index also correlated significantly with tumor stage (P = 0.002). Conclusion: Clinical information and histological features are equally important in the accurate diagnosis of MF. Papillary dermal fibrosis is a useful diagnostic clue. CD4:CD8 ratio is not increased in all cases; it may be decreased or remain unchanged.

Background Parathyroid cancer is a rare cause of primary hyperparathyroidism. It presents a diagnostic and therapeutic challenge that may not be recognized preoperatively, and is often not conclusively identified during the operation. We present the case of a lady with backache and hypercalcemia, but with inadequate work-up for her condition for several years. Case presentation A middle aged lady of Asian descent presented with backache. Initial work up revealed mild hypercalcemia, negative work up for multiple myeloma, negative sestamibi scan for parathyroid pathology. A phenomenally elevated parathormone (PTH) level—2105 pg/mL (16–87 pg/mL), and rising serum calcium, 15.1 mg/dL, (8.6–10.5 mg/dL), ordered years later prompted a repeat sestamibi scan and ultrasonography of neck. Based on these investigations, a diagnosis of primary hyperparathyroidism, with high suspicion of parathyroid cancer was made. The patient underwent surgical tumour resection, with subsequent histopathological confirmation of diagnosis. Conclusion In the setting of hypercalcemia, PTH level assessment is a must. This helps to differentiate between the parathyroid dependant and independent causes of high serum calcium, thereby encouraging a comprehensive pathway to the work up of the cause of hypercalcemia. The parathyroid cancer is a very rare cause of hypercalcemia, which needs to be considered in the differentials of primary hyperparathyroidism, particularly in the setting of high PTH levels. Electronic supplementary material The online version of this article (10.1186/s13104-018-3711-0) contains supplementary material, which is available to authorized users.

We describe our experience with an apparently immunocompetent child presenting with pyrexia of unknown origin without focal signs. Investigations revealed lymphadenopathy at lung hila, mesentery, and porta hepatis. The child had received at least two months of empiric antituberculous therapy (ATT) before she came to us. A CT-guided biopsy revealed granulomatous inflammation. PAS stain showed yeasts which stained blue with Alcian blue, suggestingC. neoformans.

Aim Ovarian steroid cell tumors, not otherwise specified (SCT-NOS) are very rare neoplasms. No large study has been performed in Pakistan to establish the clinicopathological spectrum and immunohistochemical behavior in our region. The purpose of our study was to determine the various clinicopathological and immunohistochemical features of ovarian SCT-NOS along with follow-up in our institution. Methods This was a retrospective observational study. The study was conducted in the Section of Histopathology, Aga Khan University Hospital, Karachi, Pakistan. All reported cases of ovarian SCT-NOS occurring during January 1992 to August 2013 were retrieved. The slides were reviewed and patient demographics, and clinical and pathological features were noted with proforma software. SPSS version 19 was used for all analyses. Data is expressed as absolute values and percentages. Results A total of 12 SCT-NOS (2.3%) out of 528 ovarian sex cord stromal tumors were retrieved. The age range was 3–70 years, with mean of 40.75 years. The tumors ranged 2.5–13 cm in size, with a mean size of 6.1 cm. One patient had bilateral tumors. All of the tumors were positive for inhibin and calretinin. Four tumors were negative for Mic-2 (CD99). In two patients, the tumor recurred. Only one patient who had worse pathological features received adjuvant chemotherapy. Conclusion Steroid cell tumors are very rare ovarian tumors in the Pakistani population, mostly presenting in adulthood. Diverse histological differentials exist so special stains and immunohistochemical stains are needed to distinguish these from other tumors.

Anorectal malignant melanomas (AMMs) are aggressive neoplasms, which account for less than 1% of all anorectal tumors. Anorectal malignant melanomas are notorious for their diversity of histologic features and mimic a number of other tumors. Aberrant expression of immunohistochemical stains such as cytokeratins and CD117 (c-kit) further increases the risk of misdiagnosis. Aim of our study was to describe the common as well as unusual architectural and cytologic features that create difficulty in diagnosis. We also discussed the role of immunohistochemical stains in diagnosis of AMMs. We retrieved and reviewed 61 cases of anal melanoma diagnosed in our institution between January 2005 and May 2014. Epithelioid cell type was observed in 57 (93.4%) cases, spindle cells in 35 (57.4%) cases, pleomorphic in 12 (19.7%) cases, and lymphoma-like in 2 (3.3%) cases. Cytoplasmic clearing was observed in 16.4% and nuclear pseudoinclusions in 9.8% cases. Twenty-one point three percent cases were completely amelanotic, and 36.1% showed focal melanin pigment. Average mitotic count was 2 mitoses/high-power fields. Nesting pattern was seen in 24.6%, pseudoalveolar pattern in 11.5%, and peritheliomatous/pseudopapillary pattern in 5% cases. Positive expression of vimentin, S-100, HMB-45, and Melan A was seen in 100%, 100%, 94.4%, and 93.3% cases, respectively. Cytokeratins were positive in 9% and CD117 (c-kit) in 20% of cases in which they were performed. In conclusion, AMMs should be considered in the differential of any malignant tumor of anorectal region without obvious glandular and squamoid differentiation. The knowledge of amelanotic nature, unusual histologic features, and aberrant immunohistochemical expression is helpful in avoiding misdiagnosis.

Aim: To 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. Materials and Methods: All consecutive endoscopic biopsies and resections between October 1 and December 31, 2012 were included. Results: A 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. Conclusions: Squamous 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.

Background: Errors in surgical pathology diagnosis can have serious consequences for the patient. Since the final product of a surgical pathology lab is the report, errors can be picked by reviewing reports of cases. Aim: To determine the frequency and types of error in surgical pathology reports of cases signed out in 2014 in a laboratory in Karachi, Pakistan. Materials and Methods: All surgical pathology reports in which changes were made in the original report after sign out and an amended report was issued were included. Errors included: (1) misinterpretations; (2) missing critical information; (3) erroneous critical information; (4) misidentification; and (5) typographic errors. Results: Errors were identified in 210 cases (0.37%). These comprised 199 formalin fixed specimens and 11 frozen sections. The latter represented 3.8% of a total of 2,170 frozen sections. Of the 11 frozen section errors, 10 were misinterpretations. Of the 199 permanent specimens, 99 (49.7%) were misinterpretations, 65 (32.7%) belonged to missing critical information category, 8 (4%) belonged to erroneous critical information category, 8(4%) were misidentifications, 16(8%) were typographic errors while 3 cases (1.5%) were other errors. Most misinterpretations occurred in the gastro intestinal, liver and pancreato biliary tract (23.2%) and breast (13.1%). Another 87 cases were reviewed on the clinicians' request. However diagnosis after review remained the same as the original diagnosis. In 49 out of these (56.3%), additional workup was performed at the time of the review. Conclusions: Our findings were similar to other published studies. We need to develop documented procedures for timely review of cases to detect errors.

Context There are no recent authoritative data about incidence and prevalence of various types of cancers in Pakistan. Aim To determine the frequency of malignant tumors seen in our practice and provide a foundation for building a comprehensive cancer care strategy. Materials and methods 10,000 successive cases of solid malignant tumors reported in 2014 were included. All cases had formalin fixed, paraffin embedded specimens available and diagnosis was based on histological examination of H and E stained slides plus ancillary studies at the Section of Histopathology, Department of Pathology and Laboratory Medicine, Aga Khan University Hospital, Karachi. The latest WHO classifications were used along with the latest CAP protocols for reporting and the most updated TNM staging. Results There were 9,492 (94.9%) primary tumors while 508 (5.1%) were metastatic. Some 5,153 (51.5%) were diagnosed in females and 4,847 (48.5%) in males. The commonest malignant tumors in females were breast (32%), esophagus (7%), lymphomas (6.8%), oral cavity (6.7%) and ovary (4.8%), while in males they were oral cavity (13.9%), lymphomas (12.8%), colorectum (7.9%), stomach (6.9%) and esophagus (6.6%). Malignant tumors were most common in the 5th, 6th and 7th decades. About 8% were seen under 20 years of age. Conclusions Oral cavity and gastrointestinal cancers continue to be extremely common in both genders. Breast and esophageal cancers are prevalent in females. Lung and prostate cancer are less common than in the west. Ovarian cancer was very common but cervix cancer was less so.

Objective: Parosteal Osteosarcoma (PO) is an uncommon variant of osteosarcoma. Diagnosing PO is important due to itsmalignant nature but the diversity of histologic features makes it challenging by adding a number of soft tissue, bony andcartilaginous lesions into the list of differential diagnosis. Our aim was to study the clinicopathologic and histological features ofPO with emphasis on features helpful in its discrimination from other mimicking lesions. Methods: We reviewed 23 cases of PO diagnosed in our institution between January 2001 and August 2015. Results: Femur was the most commonly involved bone (68.2%) along with other long bones and rib in a single case. Soft tissuecomponent was graded as Grade1 in 9(39%), Grade2 in 8(34.7%) and Grade3 in 4(17.3%) cases. Bony component was seeneither in combination of or exclusively as parallel streams and interconnected trabeculae (mosaic-pattern). Out of 9 cases withcartilage component, 3 showed a cartilage cap. 2(8.6%) cases showed dedifferentiation into osteosarcoma. Conclusion: PO should always be considered in the differential diagnosis of every lesion arising from the bone surface.Knowledge of the variations in histologic features helps to reach the correct diagnosis which should never be made withoutradiological correlation.

Mammary analogue secretory carcinoma (MASC) is a recently described tumor sharing the histologic, immunohistochemical, and molecular profile of secretory carcinoma of breast. We aimed to evaluate the morphologic and histochemical features needed/required for the diagnosis of MASC without adjunct of molecular analysis. Six retrospective cases suspicious for MASC and 5 prospective cases reported as MASC were included in the study. Molecular analysis of ETV6 by fluorescence in situ hybridization was performed at the University of Pittsburg, USA. The ages of the patients ranged from 9 to 60 years (mean, 27.5 years). Histologically, all tumors showed mixed growth patterns including microcystic, macrocystic, papillary, tubular, and solid, papillary the being most common pattern. The tumor cells showed round to oval vesicular nuclei with small nucleoli, and eosinophilic to vacuolated cytoplasm. All cases demonstrated luminal and cytoplasmic mucin on periodic acid-Schiff with and without diastase digestion and alcian blue stain. ETV6 fusion gene rearrangement by fluorescence in situ hybridization was detected in 10 of 11 tumors. Recurrences occurred in 3 patients, and 1 patient died of disease 5 years after surgery. In conclusion, MASC is a relatively rare salivary gland malignancy exhibiting distinct histologic and histochemical features which can help to differentiate it from other mimics. Histologically, papillary-cystic and microcystic patterns are the main clues to diagnosis. The follicular pattern of acinic cell carcinoma might represent MASC, as 4 cases in our series had this pattern. Two patients in our series were 9 and 9½ years old respectively, which are the youngest ages ever recorded for MASC.

Mixed tumors composed of schwannoma and meningioma are extremely rare and are usually associated with neurofibromatosis type 2. So far, all the cases reported have involved the cerebellopontine angle. Only 3 reported cases did not have a clear association with neurofibromatosis type 2. We report a mixed tumor comprising schwannoma admixed with meningioma and ependymoma in the cervical spinal cord of a 22-year-old male.

Background Mammary 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. Objective The aim of this study was to describe the clinical and pathological features of mammary myofibroblastoma reported at our institution. Methods Cases 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. Results A 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. Conclusions Due 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.

Uterine serous carcinoma (USC) is a rare variant of endometrial cancer that is not related to increased estrogen level; rather, it arises in a background of atrophic endometrium. Our aim was to describe clinicopathologic features of 4 cases of USC arising in endometrial polyps (EPs). The mean age of the patients at presentation was 53 years (range, 50-61 years). All patients presented with postmenopausal bleeding. In 3 patients, endometrial curretings were done before surgery, which was reported as EP with superficial foci of USC, EP with few clusters of atypical cells, and high-grade serous carcinoma, respectively. All patients underwent hysterectomy with bilateral salpingo-oophorectomy and omental sampling. The uterine cavity showed an EP in all cases ranging in size from 2 to 3.5 cm (mean, 3 cm). The hysterectomy specimens revealed USC in EP as well as the adjacent endometrium in 3 patients. The nonneoplastic endometrium was atrophic in all cases. Residual tumor was not found in the endometrium in 1 case. Omental metastatic deposits were found in all cases. Tumor deposits were also seen in the serosa of uterus, fallopian tubes, and parametrium in 1 case. Two patients died of disease 2 years after diagnosis. The remaining 2 patients are alive after a follow-up of 3 years, respectively. In conclusion, USC is a rare aggressive tumor, and to establish the diagnosis, it is important to look for the small foci of the tumor in the atrophic endometrium and on the surface of the polyps as these patients are likely to harbor additional disease in the uterus or extrauterine sites. The postmenopausal group is at high risk for developing these tumors; therefore, all the endometrial biopsies/curettings and the EPs in this age group should be thoroughly sampled.

Continued advances in the field of histo pathology (and cyto pathology) over the past two decades have resulted in dramatic changes in the manner in which these disciplines are now practiced. This is especially true in the setting of a large university hospital where the role of pathologists as clinicians (diagnosticians), undergraduate and postgraduate educators, and researchers has evolved considerably. The world around us has changed significantly during this period bringing about a considerable change in our lifestyles and the way we live. This is the world of the internet and the world-wide web, the world of Google and Wikipedia, of Youtube and Facebook where anyone can obtain any information one desires at the push of a button. The practice of histo (and cyto) pathology has also evolved in line with these changes. For those practicing this discipline in a poor, developing country these changes have been breathtaking. This is an attempt to document these changes as experienced by histo (and cyto) pathologists practicing in the biggest center for Histopathology in Pakistan, a developing country in South Asia with a large (180 million) and ever growing population. The Section of Histopathology, Department of Pathology and Microbiology at the Aga Khan University Hospital (AKUH) in Karachi, Pakistan’s largest city has since its inception in the mid-1980s transformed the way histopathology is practiced in Pakistan by incorporating modern methods and rescuing histopathology in Pakistan from the primitive and outdated groove in which it was stuck for decades. It set histopathology in Pakistan firmly on the path of modernity and change which are essential for better patient management and care through accurate and complete diagnosis and more recently prognostic and predictive information as well.

Background: Ovarian sex-cord stromal tumours (SCST) are rare, and relatively infrequent in children. These have to be distinguished from more common germ cell tumors in children and also from benign epithelial neoplasms. Objectives: The purpose of our study was to report the clinical and pathological findings in young patients with these tumours in our population. Material and Methods: The present observational cross-sectional study included all subjects

Benign metastasizing leiomyoma (BML) is a rare condition, affecting predominantly reproductive-age females with uterine leiomyomata and is most often associated with multiple benign-appearing smooth muscle tumors in lungs. We report herein a case of a 38-year-old woman who presented with multiple uterine fibroids for which hysterectomy was carried out on her. Postoperatively, she developed left-sided pleural effusion. Computed chest tomography (CT) scan revealed multiple nodules in both lungs and pleurae. Histopathology of one of the pleura-based nodules revealed a neoplasm composed of interlacing fascicles of spindle cells with uniform nuclei. The tumor cells were positive for alpha-smooth muscle actin and negative for CD34 immunohistochemical stain.

The aim of this study was to evaluate the morphological spectrum of chromophobe renal cell carcinoma (CRCC) and diagnostic utility of a panel of three immunohistochemical stains. All cases of CRCC reported between 2002 and 2012 in the Section of Histopathology, Aga Khan University Hospital, were retrieved. A total of 45 cases were identified. Slides were reviewed and immunohistochemical stains (CK7, CD117, and vimentin) were performed. Ages ranged from 18 to 90 years (mean, 48.5 years). Male-to-female ratio was 0.8:1. The tumor was located in the left kidney in 24 patients and the right kidney in 20 patients. The tumor size ranged from 3.5 to 22 cm (mean 10 cm). Histologically, 4 were classic, 22 were eosinophilic, 16 were mixed, and 3 were sarcomatoid type. Morphologic patterns included broad alveolar, solid, nested, tubular, tubulocystic, trabecular, papillary, and microglandular. Binucleation and perinuclear halos were seen in all cases. Nuclear grooves and pseudoinclusions were seen in 17 and 6 cases, respectively. Multinucleated cells were seen in 19 cases. Mitoses ranged from 1 to 11/10 HPFs (mean 3/10 HPFs). Hyalinized stroma was seen in 38 cases and calcification in 26 cases. Necrosis was seen in 18 cases. Palisading of smaller cells around the broad alveolar pattern was noted in 5 cases. The Furhman's nuclear grade was I (11), II (26), III (5), and IV (3). Hale's colloidal iron was positive in all cases. Immunohistochemical stain CK7 and CD117 were positive in 100% and 95.5% of cases respectively. Vimentin was negative in all cases, except in the sarcomatoid areas of 3 cases. In conclusion, chromophobe renal cell carcinoma has certain unique morphological features and immunohistochemical profile which help to distinguish it from conventional renal cell carcinoma and oncocytoma. We identified nuclear pseudoinclusions, microglandular pattern and palisading of smaller cells, which have not been reported earlier.

Teratocarcinosarcoma (TCS) is a rare and unusual malignant neoplasm of the sinonasal tract with a heterogenous morphology and an aggressive behavior. Patients are predominantly adults with a male predominance. The aim of this study was to describe clinicopathologic and immunohistochemical features of 6 cases of TCS. The ages ranged from 18 to 67 years (mean, 33 years) with a male-to-female ratio of 5:1. Most tumors were located in the nasal cavity. Nasal obstruction and epistaxis were the common presenting symptoms. Histologically, all tumors exhibited a heterogeneous morphology with varying proportions of benign and malignant epithelial, mesenchymal, and neuroepithelial elements. Adenocarcinoma was the malignant epithelial component in all cases. The mesenchymal elements were composed of benign to malignant spindle cells. Osteosarcomatous areas were seen in 2 cases and rhabdomyosarcoma in 1 case. Rhabdoid differentiation was also seen in 1 case. Immunohistochemical stains CKAE1/AE3 and CK Cam 5.2 were positive in the epithelial elements, vimentin in mesenchymal, and CD56 and neuron-specific enolase in neuroepithelial elements. Follow-up was available in 4 patients and ranged from 21 to 40 months (mean, 31 months). Lung and dura metastasis, respectively, were seen in 1 patient each. However, all 4 patients are alive and free of disease to date. In conclusion, TCS is a rare but highly malignant tumor with aggressive behavior characterized by benign and malignant epithelial, mesenchymal, and neuroepithelial components. Two patients in our series were younger than 20 years. The occurrence of rhabdoid differentiation and osteosarcomatous component seen in our series were rarely described in literature. Recognition of all the components requires adequate sampling, which is crucial for a correct diagnosis.

Primary carcinomas of small intestine are rare, and most are adenocarcinomas. Duodenum is the commonest site. Primary squamous cell carcinomas are exceptional. Small intestine, however, is the commonest site for metastatic spread in the gastrointestinal tract. Both adeno and squamous cell carcinoma from a wide variety of sites can metastasise to the small intestine. The authors report a case of a squamous cell carcinoma arising in the ileum of a 65-year-old woman.

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.

Background Atypical carcinoid arising from the mediastinal tissue is a rare neuroendocrine tumor and an association with parathyroid adenoma is very unusual. We report an unusual case of atypical carcinoid of mediastinum with metastasis in a patient presenting with parathyroid adenoma, which is the first case to be reported from Pakistan. Case presentation A 51-year-old Pakistani man was seen in postoperative intensive care after right parathyroidectomy and mediastinal mass resection for the management of postoperative hypocalcaemia. He had a background history of dyspnea. Examination was unremarkable. Preoperative laboratory evaluation revealed a calcium level of 12.7 mg/dl, phosphate of 1.9 mg/dl, serum albumin of 4.8 g/dl, alkaline phosphate of 94 U/L, and serum intact parathyroid hormone level 413.8 pg/ml. A technetium-99m sestamibi parathyroid scan showed right parathyroid increased tracer uptake. Further workup revealed a large mediastinal mass which was diagnosed as atypical carcinoid after Tru-Cut biopsy. He underwent right-sided parathyroidectomy and resection of the mediastinal mass. The histopathology confirmed it to be a parathyroid adenoma and atypical carcinoid tumor of his mediastinum with metastasis in his lymph node and parathyroid gland. Somatostatin receptor scintigraphy revealed a well-defined focus in his left hypochondriac region consistent with a somatostatin receptor scintigraphy-avid tumor. He was started on everolimus and planned for octreotide therapy. Conclusions We describe an incidental finding of atypical carcinoid of the mediastinum in a patient diagnosed as having parathyroid adenoma. Clinical manifestations of neuroendocrine syndromes are challenging. Some tumors cluster in a non-classic description with other common neoplasms. They rarely present in isolation, remain clinically silent, and need aggressive workup with the aid of imaging and histopathology.

Background Ovarian sex cord stromal tumors are rare neoplasms as compared to epithelial tumors. No large study has been done in Pakistan to find out the frequencies of various sex cord stromal tumors and their clinicopathological behavior in our region. The purpose of our study was to determine the various histological patterns and clinical features of ovarian sex cord stromal tumors along with follow-up in our set-up. Methods It is a retrospective observational study. The study was conducted in section of Histopathology, Aga Khan University Hospital, Karachi, Pakistan. All reported cases of sex cord stromal tumors of ovary during 1992 to 2012 were retrieved. The retrieved slides were reviewed and patient demographics, clinical and pathological features were noted on proforma. SPSS Statistics Version 19 was used for all analyses. Data is expressed as absolute values and percentage or as mean ± standard deviation (SD). Results A total of 480 cases of sex cord stromal tumors were retrieved. The median age was 45 years. Bilaterality was observed in 4 cases. Of the different subtypes of sex-cord stromal tumors, most common was adult granulosa cell tumor 211(43.9%). 24 Juvenile granulosa cell tumors were retrieved (5%). Other types were fibromas 98 (20.4%) fibrothecomas 47(9.8%), thecomas 26(5.4%), sertoli-leydig cell tumors 34(7%), sclerosing stromal tumors 26 (5.4%), steroid cell tumors (10) and 4 cases of sex cord tumor with annular tubules. Of various immunohistochemical stains applied, Inhibin was frequently positive in all subtypes and focal cytokeratins were also seen commonly. Follow up information was available in 305 cases and out of these only 16 (5%) developed recurrence or metastasis. Conclusions Sex cord stromal tumors are uncommon ovarian tumors in Pakistani population, with wide age range and diverse histological types having good prognosis. Immunohistochemical markers overlap with epithelial tumors so there is need to distinguish these two.