Diagnostic utility of anti-thyroid peroxidase immunohistochemistry in the identification of papillary thyroid carcinoma.

The routine histomorphological assessment of follicular thyroid neoplasms has been subject to interobserver or intraobserver variability among histopathologists. Anti-thyroid peroxidase (anti-TPO) has emerged as a useful immunohistochemical (IHC) marker, with its expression lost in papillary thyroid carcinoma (PTC). Our study aims to determine the diagnostic accuracy of anti-TPO IHC expression in the identifying PTC and its variants, particularly the Follicular variant of papillary thyroid carcinoma (FVPTC), with H&E assessment as the gold standard. Anti-TPO IHC (DAKO-MoAb47) was performed on 110 cases, including 76 malignant tumors (classic PTC, FVPTC, follicular carcinoma (FC), and oncocytic carcinoma (OC)) and 34 benign tumors (non-invasive follicular tumor with papillary-like nuclear features (NIFTP) and follicular adenoma (FA)). The loss of expression in more than or equal to 51 % of thyrocytes was considered suggestive of a PTC profile. The sensitivity of the loss of anti-TPO expression for identifying PTC among all carcinomas was 61.7 %, specificity was 75 %, positive predictive value was 90.2 %, negative predictive value was 34.2 %, and accuracy was 64.4 %. The loss of anti-TPO IHC expression combined with routine H&E assessment, supports the identification of PTC and its variants.

Utility of MUC4 in the diagnosis of secretory carcinoma of salivary glands.

Salivary gland tumors are diverse in morphology and both benign and malignant tumors may pose diagnostic challenges especially in small biopsies. Secretory carcinoma (SC) is histologically characterized by microcysts, follicles, solid growth pattern and occasional papillary structures, and absence of zymogen granules. SC is molecularly defined by the presence of novel gene fusion ETV6::NTRK3. Among the positive stains (S100 and mammaglobin), MUC4 is now another promising marker for the diagnosis of SC, that would enable the pathologists to exclude other morphologically close simulators. Aim of this study was to report clinicopathological features and assess utility of MUC4 in the diagnosis of SC. MUC4 was performed on 22 cases of SC. Glass slides were reviewed to record morphological patterns and staining of S100, mammaglobin, DOG1 and MUC4. Age ranged from 9 to 63 years with mean age of 34.41 ± 16.28 years. The male: female ratio was 72.7 %:27.3 %. The majority occurred in major salivary glands. A combination of patterns was seen; microfollicles were the most prevalent (90 %) followed by papillary-cystic and macrofollicles. MUC4 was positive in 19/21 (90 %) cases with almost equal number of 2+ and 3+ staining. MUC4 was negative in all cases of acinic cell carcinoma, polymorphous adenocarcinoma, adenoid cystic carcinoma, salivary duct carcinoma, myopepithelioma and myoeithelial carcinoma, cystadenoma and cribriform adenocarcinoma and all except 3 cases of mucoepidermoid carcinoma tested. Overall sensitivity of MUC4 was 95.4 %, specificity 90 %, p-value being <0.01, positive predictive value 87.5 % and negative predictive value 96.4 %. A characteristic cytoplasmic granular pattern was observed in 76.1 % tumors. S100 and mammaglobin were positive in all the performed cases. DOG1 was positive in 6/11 (28.5 %) tumors. In conclusion, MUC4 is a useful addition to a diagnostic immunohistochemical panel for SC, and to distinguish it from close potential mimickers such as acinic cell carcinoma, especially in practice settings where molecular testing is unavailable.

Assessing the biological potential of new symmetrical ferrocene based bisthiourea analogues.

In the present work synthesis and characterization of five new bisferrocenyl bisthiourea analogues (G2M, S2M, G3F, G4F and T2M) is reported. UV-Visible and electrochemical studies were performed in order to have optical (absorption maximum, Molar absorption coefficient and optical band gap) and electrochemical parameters (Oxidation/reduction potentials and nature of the electrochemical process) of the compounds. In vitro various biological studies such as antibacterial, antifungal, anti-oxidant and antidiabetic activities were carried out to have comparative overview of the phermacochemical strength of the newly synthesized compounds. Similarly, theoretical analysis was accomplished utilizing density functional theory calculations. DFT/B3LYP (6-31G d, p) technique was used. With a view to explore the structure activity relationship (SAR) of the compounds theoretical docking analysis (against α-amylase, α-glucosidase) was also performed to have pictorial view and understanding of the actual interactions responsible for the activity. S2M displayed best antibacterial activity. Similarly, Antifungal and antidiabetic activities showed G3F as a best candidate, whereas T2M proved to be the best antioxidant agent.

Thyroid cytology in Pakistan: An institutional audit of the atypia of undetermined significance/follicular lesion of undetermined significance category.

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.

Glomangiopericytoma: A rare tumour of sinonasal cavity.

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.

Non Invasive Follicular Thyroid Neoplasm with Papillary like nuclear features (NIFTP), A time for change in Pakistan.

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.

Cancer prevalence in Pakistan: meta-analysis of various published studies to determine variation in cancer figures resulting from marked population heterogeneity in different parts of the country.

BACKGROUND: Pakistan's population is ethnically diverse with distinct ethnic groups inhabiting various parts of the country. Cancer statistics obtained from specific regions populated by distinct ethnic groups may vary considerably. There is no national cancer registry. To determine whether there are indeed significant statistical differences in cancer incidence and prevalence, data was recorded from different parts of Pakistan based on the ethnic composition of the population in those parts. METHODS: Ten papers (original articles) on cancer incidence and prevalence in Pakistan published in the last two decades were selected from PubMed and Google Scholar. Meta-analysis of findings of these studies was performed using Meta-analysis of Observational Studies in Epidemiology (MOOSE) checklist. χ2-based I2 test was used for evaluating heterogeneity and Forest plots were generated for calculating unadjusted prevalence estimates. Oral, gastric, prostate, breast, and colorectal cancers were selected for meta-analysis. I2 values of 75% or greater indicated high heterogeneity. RESULTS: All five types of cancer selected for meta-analysis (performed on studies carrying similar statistical weights) showed extremely high heterogeneity with I2 values of 99.7% for oral cancer, 98.6% for prostate cancer, 98.3% for gastric cancer, 99.8% for breast cancer, and 85.4% for colorectal cancer. p values for all cancers were highly statistically significant. CONCLUSIONS: Our findings show that the prevalence rates of different cancer types demonstrate marked variation in different studies depending on the place of origin of the study and dominant ethnic group in that region, and these variations are highly statistically significant. A national cancer registry needs to be established as soon as possible.

Facile synthesis of fluoro, methoxy, and methyl substituted ferrocene-based urea complexes as potential therapeutic agents.

In the present work, the synthesis, characterization (FT-IR, multinuclear (1H and 13C) NMR, AAS, Raman, and elemental analysis), DNA binding (cyclic voltammetry, UV-Vis spectroscopy and viscometry), and in vitro biological assessment of nine new ferrocene-based ureas are reported. The desulphurization of ferrocenyl thioureas to the corresponding oxo analogues using aqueous sodium hydroxide and mercuric chloride led to the ferrocenyl ureas (F1-F9) in high yields. The DNA binding studies performed by cyclic voltammetry and UV-Vis spectroscopy produced results that are in close agreement with one another for the binding constants (K) and an electrostatic mode of interaction was observed. The nature and the extent of interaction with DNA was further investigated by viscometry. The DFT/B3LYP method was used to determine the charge distribution and HOMO/LUMO energies of the optimized structure. The DFT calculated HOMO and LUMO energies correlate well with the experimentally determined redox potential values. The synthesized ferrocenyl derivatives exhibited good scavenging activity against 1,1-diphenyl-2-picrylhydrazyl radical (DPPH). These complexes were also scanned for their in vitro cytotoxicity against human carcinoma cell line THP-1 (leukemia cells). The results showed a moderate level of cytotoxicity against the subjected cancer cell line as compared with the standard chemotherapeutic drug (cisplatin).

Enterobius vermicularis in tubo-ovarian abscess: A rare and interesting incidental finding - A case Report.

Enterobius vermicularis is a common intestinal nematode; however, rare extraintestinal Enterobius infections have been reported from different parts of the world. Here, we present a case of tubo-ovarian abscess in an otherwise healthy young sexually active female with no known comorbids with history of on and off lower abdominal pain for one year and high grade fever for one month. On the basis of further workup and radiological evaluation, a preoperative diagnosis of right sided tubo-ovarian abscess was made and salpingo-oophorectomy was performed laproscopically in July 2015. Histopathology of the resected tissue revealed necrosis and in one area Enterobius vermicularis was identified surrounded by neutrophils and eosinophil rich abscess. A final diagnosis of severe acute and chronic salpingo-oophoritis with abscess formation, secondary to Enterobius vermicularis was made. Signs and symptoms of parasitic involvement in tubo-ovarian abscesses are not much different than usual presentations of pelvic inflammatory diseases and identification of a parasite in a tubo-ovarian tissue sample is a rare clinical finding. A high index of suspicion on the part of histopathologist as well as clinician is important for timely diagnosis and effective management of such cases.

Mammary analogue secretory carcinoma of salivary glands: a clinicopathologic study of 11 cases.

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.

Olfactory neuroblastoma: A clinicopathological experience of a rare entity from Pakistan.

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.

Ovarian steroid cell tumor, not otherwise specified: a clinicopathological and immunohistochemical experience of 12 cases.

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.

Malignant melanoma of anorectal region: a clinicopathologic study of 61 cases.

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.

Dermatofibrosarcoma protuberans of the breast.

Dermatofibrosarcoma protuberans (DFSP) of the breast is an infrequent soft tissue sarcoma that usually affects young to middle-aged women. Our case report describes a unique occurrence of DFSP of the breast in an adolescent girl, which was initially being managed as a keloid for 2 years under dermatology despite being refractory to treatment. Once the diagnosis of DFSP was confirmed through punch biopsy, our patient underwent surgical excision of the lesion under general anaesthesia. Our patient was at an increased risk of damage to the ductal system due to proximity of the lesion to the nipple-areolar complex, warranting the need for early recognition and treatment. As demonstrated by our case, DFSP of the breast can be difficult to diagnose since it resembles a range of benign and malignant pathologies of the breast.

Differential analysis of histopathological and genetic markers of cancer aggressiveness, and survival difference in EBV-positive and EBV-negative prostate carcinoma.

Several studies have shown an association between prostate carcinoma (PCa) and Epstein-Barr virus (EBV); however, none of the studies so far have identified the histopathological and genetic markers of cancer aggressiveness associated with EBV in PCa tissues. In this study, we used previously characterized EBV-PCR-positive (n = 39) and EBV-negative (n = 60) PCa tissues to perform an IHC-based assessment of key histopathological and molecular markers of PCa aggressiveness (EMT markers, AR expression, perineural invasion, and lymphocytic infiltration characterization). Additionally, we investigated the differential expression of key oncogenes, EMT-associated genes, and PCa-specific oncomiRs, in EBV-positive and -negative tissues, using the qPCR array. Finally, survival benefit analysis was also performed in EBV-positive and EBV-negative PCa patients. The EBV-positive PCa exhibited a higher percentage (80%) of perineural invasion (PNI) compared to EBV-negative PCa (67.3%) samples. Similarly, a higher lymphocytic infiltration was observed in EBV-LMP1-positive PCa samples. The subset characterization of T and B cell lymphocytic infiltration showed a trend of higher intratumoral and tumor stromal lymphocytic infiltration in EBV-negative tissues compared with EBV-positive tissues. The logistic regression analysis showed that EBV-positive status was associated with decreased odds (OR = 0.07; p-value < 0.019) of CD3 intratumoral lymphocytic infiltration in PCa tissues. The analysis of IHC-based expression patterns of EMT markers showed comparable expression of all EMT markers, except vimentin, which showed higher expression in EBV-positive PCa tissues compared to EBV-negative PCa tissues. Furthermore, gene expression analysis showed a statistically significant difference (p < 0.05) in the expression of CDH1, AR, CHEK-2, CDKN-1B, and CDC-20 and oncomiRs miR-126, miR-152-3p, miR-452, miR-145-3p, miR-196a, miR-183-3p, and miR-146b in EBV-positive PCa tissues compared to EBV-negative PCa tissues. Overall, the survival proportion was comparable in both groups. The presence of EBV in the PCa tissues results in an increased expression of certain oncogenes, oncomiRs, and EMT marker (vimentin) and a decrease in CD3 ITL, which may be associated with the aggressive forms of PCa.

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.

Serous carcinoma arising in endometrial polyps: clinicopathologic study of 4 cases.

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.

Chromophobe renal cell carcinoma: a morphologic and immunohistochemical study of 45 cases.

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.

Sinonasal teratocarcinosarcoma: a clinicopathologic and immunohistochemical study of 6 cases.

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.

Left Pulmonary Artery Aneurysm Secondary to Metastatic Lung Sarcoma: A Case Report.

Aneurysms are characterized by focal dilation of the blood vessel wall due to weakening. The involvement of two layers of the vessel wall is classified as a pseudoaneurysm while the involvement of all three layers is called a true aneurysm. Involvement of neoplastic lesions is rare, but the few reported cases have been associated with pulmonary artery pseudoaneurysms as opposed to true pulmonary artery aneurysms (PAAs). Our case of a true left PAA of a patient with metastatic sarcoma of the lung shows an association that has previously not been reported to the best of our knowledge.