Ductal carcinoma in situ and invasive carcinoma originating in a Fibroadenoma with concurrent benign phyllodes tumor: A case report.

INTRODUCTION AND IMPORTANCE: This case report presents a rare occurrence of multiple bilateral breast fibroadenomas, one evolving into ductal carcinoma in situ (DCIS) and invasive carcinoma, occurring simultaneously with a benign phyllodes tumor in the same breast. The importance of this case lies in emphasizing the crucial need for surveillance in patients with a long history of fibroadenomas and the necessity to investigate any rapid change in the size of fibroadenoma. CASE PRESENTATION: A 35-year-old multiparous female with a 17 year history of bilateral multiple breast lumps presented with recent onset of right breast pain and yellowish nipple discharge. Two lumps in her right breast had demonstrated an increase in size. Examination revealed a significant mass in the retroareolar region of the right breast and another at the 2 o'clock position. Histopathological examination of the biopsy specimens revealed fibroadenoma and benign phyllodes tumor. The patient underwent a bilateral breast lumpectomy. Further histopathological examination revealed ductal carcinoma in situ and invasive carcinoma within a complex fibroadenoma in the right breast and benign phyllodes tumor. Sentinel lymph node biopsy was negative. She had adjuvant radiations and trastuzumab. Regular follow-ups show no recurrence. CLINICAL DISCUSSION: Fibroadenomas are usually benign but rarely undergo malignant change. Quick response to size changes and early detection greatly enhance patient results. CONCLUSION: Ductal carcinoma in situ and invasive breast cancer, a rare malignancy found within a fibroadenoma, necessitates histopathological specimens and immunohistochemical results for accurate diagnosis. Survival rates are significantly enhanced through a multidisciplinary approach.

Correlation between HER2/neu protein overexpression on Immunohistochemistry and Fluorescent in Situ Hybridization (FISH) in breast carcinoma: Problems in developing countries.

Objective: To correlate the results of HER2/neu protein overexpression on immunohistochemistry (IHC) and gene amplification on fluorescence in situ hybridization (FISH) and to document the problems faced in performing FISH procedure. Methods: This was an observational retrospective study covering five years from January 1st, 2015 - December 31st, 2019 at Histopathology Department of Shifa International Hospital (SIH), Islamabad. All cases of breast cancer that underwent florescence in situ hybridization (FISH) were retrieved. Correlation between HER2/neu overexpression on IHC and its amplification on FISH was analyzed. Problems in application of FISH were recorded. Results: Out of 451 cases submitted for HER2/neu testing by FISH, 68 cases (15%) were rejected. Gene amplification was seen in 139 (36.29%) cases. Total cases with HER2/neu IHC score of 2+ were 330 cases and out of which gene amplification was seen in 98 cases (29.69%) whereas 93.1% (41/44) 3+ IHC cases were amplified. Poor fixation, inadequate amount of tumor with crushing artefacts and dye application to the biopsy fragments were causes of sample rejection. Conclusions: Her2/neu amplification was seen in most Her2/neu 3+ cases and approximately one-third of Her2neu 2+ cases. Proper fixation, adequate biopsy material with standardized processing is required to yield useful results on FISH.

The gastrointestinal basidiobolomycosis, a rare entity: Case report and review of literature.

Gastrointestinal basisdiobolomycosis is a rare fungal infection prevalent in the tropical and subtropical regions. It has variable clinical manifestations that present a challenge for timely diagnosis. Herein, we present a case of gastrointestinal basidiobolomycosis in a 34-year-old male. To the best of our knowledge, it is the first reported case of gastrointestinal basidiobolomycosis from Pakistan. The patient presented with abdominal pain and was first operated for perforated appendix and then for a mesenteric mass based on the findings of CT scan. Histopathologic examination showed broad septate fungal hyphae surrounded by eosinophilic proteinaceous material (Splendore-Hoppeli phenomenon), neutrophils, and histiocytes. Diagnosis of gastrointestinal basidiobolomycosis was established on the basis of this morphology.

Port site tuberculosis a rare post operation entity: A case report.

Laparoscopic cholecystectomy is one of the most common procedures done worldwide. Post-surgical site infections are common, yet there are occurrences of uncommon complications, including port site tuberculosis (TB). We report a case of a 62-year-old man who was the victim of post-surgical site infection of port sites caused probably by improper sterilization. The patient lacked any common symptoms of tuberculosis and his initial lab investigations were not affirmative. A biopsy depicting the growth of multiple epithelioid granulomas finally led to the diagnosis of port site tuberculosis. The patient was treated by incision and drainage followed by anti-tubercular therapy. This treatment regime showed complete resolution of disease on follow-ups. Such cases require multidisciplinary team (Surgery, Pathology and Infectious disease department in our case) inputs for prompt diagnosis and treatment.

Primary Breast Mucinous Cystadenocarcinoma and Review of Literature.

Mucinous cystadenocarcinoma of the breast is a rare primary breast carcinoma having distinct clinical behavior and a favorable prognosis. It has a characteristic morphology that must be differentiated from metastatic ovarian and pancreatic mucinous adenocarcinoma. The etio-pathogenesis, genetic profile, and treatment of this tumor are controversial. Here, we report a case of primary mucinous cystadenocarcinoma of the breast in a 61-year-old female. The case is of interest since it is uncommon and has peculiar clinical and morphological features.

Giardiasis: An Overlooked Cause of Recurrent Abdominal Pain.

Recurrent abdominal pain is defined as at least three episodes of abdominal pain, lasting for three months or more and affecting the daily activities of an individual. Giardiasis is one of the causes of recurrent abdominal pain but is often overlooked. We report the case of an 11-year-old girl who presented with complaints of severe abdominal pain and two episodes of fresh blood in stool in one day. She had recurrent episodes of abdominal pain, occasional bloating, and diarrhea over the past two years. Workup for differentials like appendicitis and ovarian torsion was done. She was initially treated for an ovarian cyst with oral contraceptives, but her symptoms showed no improvement. Therefore, a laparoscopic ovarian cystectomy and appendectomy were attempted. Despite surgical intervention, the abdominal pain failed to resolve. A duodenal biopsy was performed, which showed vegetative growths of Giardia lamblia (G. lamblia). This report highlights the unusual presentation of giardiasis as an acute abdomen, making it a diagnostic challenge.

Lung Biopsy in Coronavirus-19 Pneumonia: A Case Report and Review of Literature.

Pneumonia is one of the major manifestations of infection by the novel coronavirus (COVID-19) virus. CT scans are used as first line investigation in suspected cases. Biopsies are almost never done. The gross and microscopic pathology has been studied mostly on autopsy specimens in fatal cases. We present a case of a mildly symptomatic adult male, who was a chronic liver disease patient awaiting liver transplant. His lung biopsy was done for diagnosis of a lesion, suspected to be a fungal infection. He was tested for COVID-19 and was PCR-negative at the time. His biopsy showed patchy changes of viral pneumonia. One week later, he tested positive for COVID-19 on PCR. He became asymptomatic soon and the ground glass lung opacities cleared up within another week without any treatment in spite of having a serious comorbid condition.   Key Words: Viral pneumonia, COVID-19, Lung biopsy.

Gastroenteropancreatic neuroendocrine tumours: Clinicopathological evaluation at Shifa International Hospital, Islamabad.

OBJECTIVE: Clinicopathological features of gastroenteropancreatic neuroendocrine tumours (GEP-NETs) have rarely been studied in Pakistani population. We investigated clinical characteristics of these tumours according to updated World Health Organization (WHO) 2010 classification. METHODS: The data of Shifa International Hospital, Islamabad was retrospectively analysed for pathologically confirmed GEP-NETs from January 2013 to March 2018. RESULTS: One hundred and eighteen patients (mean age, 52.2± 16.4 years; Of these 65(55.1%) were males. Majority, 98(83.1%) of the patients were symptomatic including 6(5.1%) with functional tumours. Pancreas was the most frequent primary site noted in 33(28%) patients. The most common histologic type was well differentiated neuroendocrine tumour (WDNET) in 96(81.4%) patients followed by neuroendocrine carcinoma (NEC) in 11(16.1%) patients. Almost half the cases or 54(45.8%) of WDNET were grade 1, 32 (27.1%) were grade 2, and 10 (8.5%) were grade 3. Distant metastasis at the time of diagnosis was found in 18(15.3%) cases with 14,(77.7%) in liver as the most common metastatic site. Synaptophysin positivity was seen in 60 (96.8%) cases of grade 1, 32(27.2%) of grade 2 WDNET, 8(100%) cases of grade 3 WDNET and 12(92.3%) of NEC and chromogranin was positive in 49(94.2%) of grade 1 and grade 2 WDNET, 5 (83.3%) cases of grade 3 WDNET and 5 (45.4%) cases of NEC. CONCLUSIONS: GEP-NETs showed a wide clinicopathological spectrum. Pancreas is the most common site of involvement by the GEP-NET, however, grade 3 WDNET had a predilection for colon. Small cell carcinoma was commonly observed in the oesophagus.

Small-cell neuroendocrine carcinoma of the urinary bladder: A case report.

Primary neuroendocrine carcinomas of the urinary bladder are rare. A 60-year-old male presented with gross hematuria for the past 3 months. Diagnostic flexible cystoscopy revealed a papillary lesion above the right ureteric orifice. Transurethral resection of bladder tumor was performed and resected tissue was sent for histopathology that revealed high-grade urothelial carcinoma with small-cell neuroendocrine differentiation. Lamina propria, muscularis propria, and perineural invasion was seen which was later also confirmed by immunohistochemistry. The patient received neoadjuvant four cycles of chemotherapy and then underwent radical cystoprostatectomy with ileal conduit. The patient's recovery was uneventful and he is on regular follow-up from the past 12 months without any disease recurrence. Early detection and aggressive management can improve the survival and prognosis of these patients.

Is TLE1 Expression Limited to Synovial Sarcoma? Our Experience at Shifa International Hospital, Pakistan.

INTRODUCTION: Synovial sarcoma (SS) accounts for 10-15 percent of adult soft tissue sarcomas. Transducin-like enhancer of split 1 (TLE1), a transcriptional repressor, is essential in hematopoiesis, neuronal differentiation, and terminal epithelial differentiation. TLE1 proteins inhibit Wnt signaling and other cell fate determination signals, and so have an established role in repressing differentiation. TLE1 has recently been shown to be a highly sensitive and relatively specific marker of SS. MATERIALS AND METHODS: Study design is retrospective, descriptive. A total of 25 cases of SS and 28 of soft tissue lesions were retrieved from the record. TLE1 (clone 1F5) expression was evaluated and scored as negative (<5% of cells positive), 1+ (5-25% of cells positive), 2+ (26-50% of cells positive), or 3+ (>50 % of cells positive). RESULT: Twenty-four out of twenty-five (96%) cases of SS showed 3+ TLE1 expression. One (4%) case of poorly differentiated SS showed 2+ positivity. 3+ TLE1 positivity was seen in one (100%) case each of infantile fibrosarcoma and low-grade fibromyxoid sarcoma, while two cases (100%) of schwannoma also showed 3+ positivity. All cases of solitary fibrous tumor) (n=2), clear cell sarcoma of tendons and aponeurosis (n=2), embryonal rhabdomyosarcoma (n=1), and de-differentiated liposarcoma (n=2) showed 2+ positivity. 1+ positivity was seen in alveolar soft part sarcoma (n=2), Ewing's sarcoma (n=4), undifferentiated pleomorphic sarcoma (n=1), myxoid liposarcoma (n=1) and malignant peripheral nerve sheath tumor (n=1). TLE1 was negative in all cases of chordomas (n=2), lipomas (n=2), nodular fasciitis (n=2), malignant perivascular epithelioid cell tumor (n=1) and dermatofibrosarcoma protuberans (n=1). CONCLUSION: TLE1 may be a reliable immunostain for diagnosing SS, but its expression is not limited to SS. Its expression should be interpreted in the light of morphological features and a panel of antibodies.

Role Of Immunohistochemistry In Subtyping Renal Cell Carcinomas With Overlapping Morphological Features.

BACKGROUND: Renal cell carcinoma (RCC), accounts for 2-3% of all new cancers diagnosed. Most renal tumours have characteristic histological features, which help in their sub classification. However, some cases do show overlapping morphology which pose a diagnostic challenge for the pathologists. Tumour ancillary studies such as immunohistochemistry (IHC) may play a significant role in segregation of these tumours. This study was undertaken to determine the role of IHC in diagnosing these tumours. METHODS: December 2015. It was carried out in histopathology laboratory of Shifa International Hospital, Islamabad. A total of fifty-five (n=55) nephrectomy specimens having RCC subtypes were included. A specific morphological diagnosis was rendered in each case on H&E.. A panel of six immunohistochemical markers CK7, CD10, CD117, CA IX, AMACR and Vimentin was then applied in each case and a final diagnosis considering both morphology and IHC was given. Statistical analysis was done using SPSS version 20.0. Mean and SD were calculated for quantitative variables where as frequencies and percentages were calculated for qualitative variables. RESULTS: Out of a total of 55 cases, 36 (65.55%) were males whereas 19 (34.5%) were females. The mean age of patients was 54.04±14.40 years. Clear cell RCC comprised 70.9% (n=39), Papillary RCC 14.5% (n=8), Chromophobe RCC 10.9% (n=6) and clear cell papillary RCC 3.6% (n=2) of cases on morphology. After application of IHC stains in all cases, 83.6% (n=46) of cases were found to have correct diagnosis on H& E. However, 16.4% (n=9) of cases could not be correctly diagnosed on morphology alone and it was in these cases that IHC played a major role in reaching a final diagnosis. CONCLUSIONS: Although most RCC subtypes display a characteristic morphology on H&E, in a significant proportion of the cases there are considerable overlapping morphological features. Our study shows that a correct diagnosis cannot be made on H & E alone in a notable number of cases. Therefore, IHC should be applied in all cases to reach a final diagnosis, which has both prognostic and therapeutic implications.

An Unusual Presentation of Langerhans Cell Histiocytosis.

Langerhans cell histiocytosis (LCH) is a rare entity formerly known as eosinophilic granuloma. It is characterised by clonal multiplication of langerhans cells (LCs) that can occur anywhere in the body, especially in connective tissue of skin, lymph nodes and bone. Although rare, the disorder frequently affects children. A 7-year male child presented with the complaint of swelling at glabella. CT-scan revealed a defect in the middle of both frontal bones with brain herniating out of it. The clinical differential diagnosis included osteomyelitis, Tuberculosis and encephalocele. Fine needle aspiration cytology (FNAC) was performed and diagnosis of LCH was confirmed by typical cytological features, followed by immuno- histochemical staining for CD1a.

Whipple Resection: Concordance Between Frozen Section And Permanent Section Diagnosis Of Surgical Margins.

BACKGROUND: Margin assessment is done in Whipple procedures which are usually performed to resect tumours of head of pancreas and ampullary/periampullary region. Aims and objective of the study are to determine the concordance between frozen sections (FS) and permanent sections (PS) of surgical margins in Whipple resections. METHODS: It is a retrospective study, from January 2008 to January 2015 (07 years). It includes the specimen with malignancy in final report and for which FS of pancreatic and/or CBD margin(s) were requested. Data was retrieved from Laboratory information system (LIS) database. RESULTS: Of the 41 bile duct margins in cases of ampullary tumours, 03 were positive on FS as well as PS, 35 were negative on FS as well as on PS. Results showed 100% sensitivity, 92.1% specificity, 50% PPV and 100% NPV. Results of 36 pancreatic margins in cases of ampullary showed 100% sensitivity, 97.1% specificity, 50% PPV and 100% NPV. In pancreatic carcinoma cases, none of CBD margins were reported as positive on FS, 02 margins reported as negative were found positive on PS, while 17 were negative on FS as well as PS. Results showed 100% specificity and 89.5% NPV. Of the 27 pancreatic margins tested in pancreatic tumours 100% sensitivity, 94.1% specificity, 88.9% PPV and 100% NPV was found. CONCLUSIONS: Factors such as absent prior tissue diagnosis and/or inflammatory processes make margin diagnosis difficult. However, a high concordance was observed between our FS and PS diagnosis.

Primary Renal Epithelioid Angiosarcoma.

Primary renal angiosarcoma is a rare tumor. Epithelioid variant of primary renal angiosarcoma is extremely rare and aggressive entity described in literature as a few case reports. It presents as solid looking renal mass as other renal cell carcinomas. Management is not well described due to scarcity of cases and aggressiveness of disease. We hereby report a case of epithelioid renal angiosarcoma in a 62-year female who presented with features of infected perinephric collection. Histopathological and immunohistochemical examinations of the renal specimen revealed lower polar renal tumor with atypical epithelioid cells having eccentric nuclei with coarse chromatin and eosinophilic cytoplasm, which were positive for vascular endothelial (FLI-1, CD 34, CD31 and factor VII) as well as epithelial (CKAE1/AE3) immune markers. Based on the histopathological and immunohistochemical findings, the patient was diagnosed with primary renal epithelioid angiosarcoma.

Follicular dendritic cell sarcoma presenting as colonic intussusception.

Follicular dendritic cell sarcoma (FDCS) is a rare intermediate grade sarcoma involving a variety of nodal and extra nodal sites. It has two histological subtypes, conventional and inflammatory pseudotumour like variant. We report this interesting case of FDCS presenting colonic intussusception at Shifa International Hospital, Islamabad, Pakistan. Conventional FDCS presenting as a colocolic intussusception is an unusual presentation, and to our knowledge, has never been reported previously. It has wide morphological spectrum on light microscopy and has characteristic immune-reactivity for dendritic cell markers (CD21, CD23, and CD35). Surgical excision is required in all cases while role of adjuvant chemotherapy and radiotherapy is not clearly demonstrated in literature.

Sex cord stromal tumours of the ovary, experience at Shifa International Hospital Islamabad.

This descriptive study was carried out at Pathology Department, Shifa International Hospital from 2007 to 2016; all sex cord stromal tumours diagnosed during this time period were included. Epithelial, germ cell and metastatic tumours were excluded from the study. A total of 1254 Ovarian tumours were brought to Shifa of which47 (4%) were labeled as sex cord stromal tumours. Of these 36( 76 %)were granulosa cell tumour (adult33, juvenile3), 7 were labeled as sertoli leydig cell tumours (15%), 3 as thecoma/ fibroma group (7%)and only one case was labeled as microcystic stromal tumour of the ovary (2%). Overall age range for sex cord stromal tumours was 42 (12-71). Immunohistochemistry was done in 41 out of 47 cases. Sex cord stromal tumours of the ovary are rare tumours comprising 4% of the total. Adult Granulosa cell tumour is the commonest tumour seen in our study.

Anterior abdominal wall extraosseous osteosarcoma, occurring 40 years after para-aortic irradiation.

Extraskeletal osteosarcomas (OSs) are highly malignant soft tissue tumours associated with a poor prognosis. Only a few records of these rare aggressive neoplasms have been reported in the literature.We describe the case of a 49-year-old man, who presented to our tertiary care centre with a painful isolated lump around the umbilicus. After surgical biopsy, imaging and subsequent pathological analysis, the swelling was diagnosed to be a localised extraskeletal OS. He received previous radiation as treatment for testicular seminoma 40 years ago, which has been in remission ever since. He also happens to have testicular hydrocele since 10 years. He was subjected to resection and free flap reconstruction complicated by lower anterior abdominal wall haematoma and large pseudoaneurysm of the left femoral artery. Patient completed 60 Gy of adjuvant electron beam irradiation for close margins and is scheduled for adjuvant chemotherapy. We describe a brief account of his illness.

Synchronous Inflammatory Myofibroblastic Tumor in Lung and Brain: A Case Report and Review of Literature.

Inflammatory myofibroblastic tumor (IMT) is a rare entity and a diagnostic challenge with myriad clinical presentations and pathogenetic mechanisms. Isolated occurrences can be at any site in the body; however, only a few cases of IMT with the concomitant appearance of different organs have been published. We report a unique occurrence of bilateral inflammatory myofibroblastic tumor of the lungs with synchronous brain parenchymal lesions in an 11-year-old male, detailing clinical presentation with the emphasis on imaging and review of the literature.

Encapsulated papillary carcinoma (EPC) of breast: A clinical, pathological and immunohistochemical analysis of eight cases.

Encapsulated papillary carcinoma (EPC) is a rare low grade carcinoma of the breast with excellent prognosis. This case series focuses on its histopathological and clinical characteristics in our material. Cases of papillary lesions of breast from 1st January 2012 to 30th December 2014 were retrieved from the hospital database. A total of 8 cases were categorized as EPC. Mean age of patients was 66 years. Breast lump with tumour size ranged from 1.5 to 5.0cm, and was the presentation in 75% of cases. Histopathology showed a well circumscribed lesion within a dilated duct comprising of fibro vascular cores lined by neoplastic cells, surrounded by thick fibrous capsule. Immunohistochemistry, for antibody panel p63, ASMA and CK 5/6 were negative for myoepithelial cells. Invasive carcinoma was seen in 3 (37.5%) with associated DCIS in 4 (50%) cases. Meticulous gross, attention to morphology and correct interpretation of immunohistochemistry are imperative for accurate diagnosis.