p16 expression in urothelial carcinoma: Experience from a tertiary care center in coastal South India.

Background: Urothelial carcinomas (UC) account for 6 and 2% of all cancers in men and women, respectively. Human papillomavirus (HPV) is one of the causative agents in cancers of the uterine cervix and head and neck. The role of HPV is also being studied in cancers of the urinary bladder, penis, and prostate. As p16-INK4a is a surrogate marker for high-risk HPVE7 oncoprotein, this study aims to highlight the utility of p16 immunohistochemistry (IHC) in the evaluation of HPV-associated UC. Materials and Methods: A retrospective study was conducted on UC of the bladder received in the Pathology department between January 2013 and December 2018. Bladder biopsies from non-neoplastic lesions served as controls. IHC was done for the detection of the p16 antigen. The p16 staining was recorded as positive, when there was strong staining in >50% of tumor nuclei. The p16 positive and negative tumors were compared based on age, gender, tumor size, grade, and muscle invasion. P value <0.05 was considered statistically significant. Results: The expression of p16 was analyzed in 72 UC and compared with 20 non-neoplastic cases, of which 26.4% of the cases showed p16 expression. The p16 expression was absent in the non-neoplastic lesions. While the majority (87.5%) of the low-grade tumors were negative for p16 expression, 43.8% high-grade tumors were positive. Similarly, a larger proportion of invasive carcinomas (38.8%) expressed p16 as compared to non-invasive carcinomas (13.8%). Thus, p16 expression showed a significant association with grade and stage in these malignancies (P < 0.05). Conclusion: The p16 expression was associated with high-grade and muscle-invasive UC. The p16 was absent in all non-neoplastic and precursor lesions. Thus, it can provide essential information not only about HPV association but also on the prognostic implications for the patients.

Study of pre-operative neutrophil-lymphocyte ratio in urothelial carcinoma.

OBJECTIVES: Neutrophil-lymphocyte ratio (NLR), as an indicator of heightened systemic inflammatory response, predicts increased disease burden and poor oncological outcomes in urothelial carcinoma (UC). The study was undertaken with an aim to evaluate the association of NLR with clinicopathological variables and survival outcomes. METHODS: A total of 80 patients of UC were enrolled in the current retrospective study. Pre-operative NLR (within one month prior to the procedure), patient age, sex, tumour grade, pathological stage, recurrence free survival (RFS), progression free survival (PFS) and cancer specific survival (CSS) were recorded. We chose a cut-off value of 2.7 for NLR and patients were divide into two groups (NLR <2.7 and ≥2.7). RESULTS: NLR ≥2.7 was significantly associated with advanced tumour stage (p=0.001), but not with tumour grade (p=0.116). Progression (p=0.032) and death rates (p=0.026) were high in patients with NLR ≥2.7. Mean RFS (p=0.03), PFS (p=0.04) and CSS (p=0.04) were reduced in patients with NLR ≥2.7. On univariate analysis, NLR ≥2.7 predicted worse RFS (HR=2.928, p=0.007), PFS (HR=3.180, p=0.006) and CSS (HR=3.109, p=0.016). However, it was not an independent predictor of outcomes on multivariate analysis. CONCLUSIONS: Tumour stage and grade are the only independent predictors of RFS, PFS and CSS. High NLR at a cut-off value of ≥2.7 is associated with advanced pathological stage, but does not have an independent predictive value for RFS, PFS and CSS.

Immunohistochemical comparison of p63 and p40 in head and neck Spindle Cell Carcinoma.

BACKGROUND: Spindle Cell Carcinoma (SpCC) is a rare type of squamous cell carcinoma (SCC) with prominent malignant spindle cell component. This unique biphasic feature on histopathological examination makes its diagnosis problematic. Detection of p63 antigens in SpCC can be helpful however its expression in variousb proliferating soft tissue lesions demands for better marker. METHODS: In this study, histopathologically diagnosed SpCC of head and neck region were considered as cases, and 22 soft tissue sarcomas, reactive lesions and spindle cell lesions of the body were taken as controls. Immunohistochemistry (IHC) was done using Anti-p63 and p40 clone and the results were compared. CK was done for negative cases to prove their epithelial origin. P. value < 0.05 considered statistically significant. RESULTS: Among 22 cases of SpCC, 19 cases showed positive immunoreactivity to p63, and 18 cases for p40. IHC of controls showed no immunoreactivity in any of the sarcomas, reactive lesions or spindle cell lesions. The sensitivity of p63 is 86% while that of p40 is 82%. Specificity of both the markers was 100% CONCLUSION: Though p63 is a slightly (4%) more sensitive marker than p40, percentage of cell positivity for p40 is higher compared to p63. Both of these markers are 100% specific for SpCC.

In pursuit of the primary.

Extraovarian primary peritoneal carcinoma (EOPPC) is a rare tumour of the peritoneum that shares many features with serous ovarian carcinoma because of a common embryological origin. We report a case of EOPPC presenting with a malignant pleural effusion. https://bit.ly/3GMuKgL.

"Read" and 'Tailor' Your Treatment.

INTRODUCTION: The sinonasal tract is an area that may be affected by various types of neoplastic lesions with more variety than what is encountered in other parts of the upper airway and food passage. CASE REPORT: An elderly gentleman of 65 years complained of nose block on both sides for 3 months. On examination, he had firm polypoidal masses arising from the middle meatus and septum on both sides. Computed tomography scan of the sinuses revealed polypoidal mucosal thickening in bilateral sinuses with bilateral concha bullosa. The patient underwent functional endoscopic sinus surgery with the complete excision of the masses from the lateral wall and septum under general anesthesia. The results of the histopathological examination showed inflammatory changes in polypoidal tissues from the right maxillary, bilateral ethmoidal sinuses, and bilateral septal masses. The lesion in the left middle meatus showed the features of respiratory epithelial adenomatoid hamartoma (READ). The case had no evidence of residual or recurrent lesion during 6 months after the surgery. CONCLUSION: The READ is a rare lesion observed in the sinonasal tract. It is a diagnostic dilemma for clinicians as it can be misdiagnosed as neoplastic lesions, such as inverted papilloma or adenocarcinoma, which would warrant radical surgery or sinonasal polyposis and be treated inadequately.

Clinicopathological spectrum of solitary Plasmacytoma: a single center experience from coastal India.

BACKGROUND: Plasma cell disorders are a rare group of hematological malignancies that accounts for 10% of all hematological neoplasms. Solitary plasmacytomas are rarer entities accounting for less than 5% of all the plasma cell dyscrasias. They encompass three subtypes - Solitary Plasmacytoma of Bone (SPB) and Solitary Extramedullary Plasmacytoma (SEP) and multiple solitary plasmacytomas (MSP). In this study, we discuss the clinical, histopathological and immunohistochemical characteristics of solitary plasmacytomas. METHODS: A 13 year retrospective analysis of solitary plasmacytomas was performed from a single tertiary care center. Bone marrow evaluation was done concurrently at the time of diagnosis to rule out the presence of multiple myeloma. RESULTS: A total of 29 cases fulfilled the diagnostic criteria for SP during the study period. SPB accounted for 55.2%, SEP for 44.4% and MSP for 3.4% of the cases. The most common sites involved were the paranasal sinuses and vertebrae. Other infrequent sites included lymph node, tonsil and lungs. The mean age of presentation of SPB was a decade later than SEP. A male preponderance was observed in both subtypes. CONCLUSION: Solitary plasmacytoma is a rare entity, the diagnosis of which requires a systematic approach. There is limited data available in the literature on the clinico-pathological characteristics of SP from India.

Utility of fine-needle aspiration cytology in the diagnosis of HIV lymphadenopathy.

BACKGROUND: India, being a developing country, harbors the third largest human immunodeficiency virus (HIV)-infected population in the world, and HIV-associated lymphadenopathy is commonly encountered. HIV lymphadenopathy is more commonly generalized and pathology ranges from reactive lymphoid hyperplasia to infections like tuberculosis to neoplasms such as lymphoma and Kaposi sarcoma. The study intended to assess the utility of fine-needle aspiration (FNA) cytology in HIV lymphadenopathy. MATERIALS AND METHODS: A retrospective FNA slide review of HIV-infected cases with lymphadenopathy received over a period of 2 years in the cytopathology department was performed. The clinicopathological characteristics, absolute lymphocyte count (ALC), and CD4 counts were analyzed. RESULTS: Seventy-nine lymph node aspirates were received from HIV patients over 2 years. The mean age at presentation was 39 years with a male:female ratio of 2.4:1. Cervical lymph nodes (62%) were more commonly affected. Tuberculous lymphadenitis was the commonest lesion (41.8%), followed by reactive lymphadenitis (24%), nonspecific granulomatous lymphadenitis (14%), suppurative lymphadenitis (8%), cryptococcal lymphadenitis (2%), lymphoma (9%), and metastasis (1%). CONCLUSION: Lymph node FNA in HIV/AIDS is not only useful in identifying those cases that require further evaluation, but also aids in categorizing various etiologies such as opportunistic infections, non-neoplastic, and neoplastic lesions. FNA is a less expensive, expeditious minimally invasive method for an early diagnosis that abets in deciding the treatment strategy, thus curtailing the associated morbidity and mortality.

Congenital Pulmonary Airway Malformation - 19-Year Experience from a Tertiary Care Center in India.

Background: Congenital pulmonary airway malformation (CPAM) is a collection of non-hereditary, developmental anomalies. Our aim was to analyze the histological profiles and prevalence of CPAMs diagnosed in our center. Methods: A retrospective study of all CPAMs diagnosed from January 1999 to May 2018 from a general hospital pathology service was performed. Results: There were 79 cystic lesions encountered in fetuses, neonates, and children, 15 of which were CPAMs {5/2372 (0.21%) autopsies and 10/216026 (0.0046%) surgical resections}. The male:female ratio was 1:1.14. Gestational age of antenatal cases ranged from 22 to 32 weeks, postnatal ages ranged from 7 days to 15 years (mean 2.9 years). The cases were right-sided (8/15;53.3%), left-sided (4/15;26.7%) and bilateral (3/15,20%). Seven (46.7%), 4 (26.7%),3 (20%) and 1 (6.7%) were types 1, 2, 3 and 4, respectively. None of the surgical cases had postoperative mortality or morbidity. Conclusions: Prompt recognition and surgical resectability resulted in normal growth and symptom free survival in our postnatally diagnosed patients. Mortality in antenatally diagnosed fetuses remains high (5/11;45%).

Image-guided Fine Needle Aspiration Cytology of Intrathoracic Lesions.

BACKGROUND: Percutaneous, image-guided transthoracic fine needle aspiration cytology (TTFNAC) is a rapid, yet accurate, and well-established diagnostic method used in the cytological evaluation of intrathoracic lesions. The study was done to determine the utility of image-guided TTFNAC in diagnosis of intrathoracic lesions. SUBJECTS AND METHODS: A retrospective analysis of all cases who underwent image-guided TTFNAC of a suspected intrathoracic lesion, in a tertiary care hospital was done over a period of 3 years. RESULTS: During the study period, 124 cases of image-guided FNAC of intrathoracic lesions were obtained. The mean age at presentation was 60.5 years with M:F: 3.6:1. Neoplastic lesions (71.5%) outnumbered the nonneoplastic lesions (28.5%). The most common tumor was adenocarcinoma (25%) followed by squamous cell carcinoma (SCC, 11%), and small cell carcinoma (5%). There was one case each of anaplastic carcinoma, plasmacytoma, bronchoalveolar carcinoma, and non-Hodgkin lymphoma (NHL). Most of the lesions were found on the right side and upper lobe. Among the mediastinal lesions, we found two cases of thymoma and one case each of NHL)/primitive neuroectodermal tumor (PNET), NHL, and small cell carcinoma metastasis to lymph node followed by ten cases of inflammatory lesions and seven cases of tuberculosis (TB). CONCLUSION: Image-guided TTFNAC of intrathoracic lesions is a safe method when done by well-trained medical personnel with lesser rate of complications. An early accurate diagnosis of malignancy can be made based on the cytological features; however, further subtyping of the malignancy may sometimes be difficult due to overlapping cytological features. TTFNAC can be a diagnostic tool for identifying nonneoplastic lesion such as TB. Hence, image-guided FNAC aids in early diagnosis and management of patients with intrathoracic lesions.

Discovered on gastrointestinal stromal tumor 1, a keystone in the diagnosis of extraintestinal gastrointestinal stromal tumors.

INTRODUCTION: Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract (GIT) but have a low incidence. Arising from the interstitial cells of Cajal, GISTs occur at different sites in the GIT with stomach being the most common. They can rarely be seen at sites outside the GIT such as omentum, retroperitoneum and are called as extraintestinal GISTs (EGIST). They have a spindle or epithelioid cell morphology and show positivity by immunohistochemistry (IHC) for CD117. Our aim was to study the clinicopathological and immunohistochemical profile of our cases of EGISTs. MATERIALS AND METHODS: A cross-sectional study of EGISTs received from 2010 to 2015 was done. IHC with CD117 and discovered on GIST1 (DOG1) was performed and tumors were scored based on the percentage of cells that stained positive. Thirteen abdominal non-GIST spindle cell tumors were included in the study as controls. RESULTS: Seven cases of EGIST were included (four-omental, three-retroperitoneal). All cases stained positive for CD117 and DOG1. One case of epithelioid EGIST scored 4 + with DOG1 and 2 + with CD117. Another case with mixed morphology scored 2 + with DOG1 and 4 + with CD117. All controls were negative for both markers. CONCLUSION: EGISTs are one of the rare differentials for spindle cell lesions outside the GIT. Although both markers stain positive, DOG1 showed higher score with epithelioid GISTs.

Evaluation of p53 protein expression in Barrett esophagus.

BACKGROUND: Loss of heterozygosity of p53 along with aneuploidy is deemed to be the early molecular steps in Barrett metaplasia-dysplasia-adenocarcinoma sequence. Objective biomarkers need to be used along with microscopy for risk stratification to predict the progression of Barrett esophagus (BE) to carcinoma. AIM: This study aims to study p53 protein expression in dysplasia and correlate the same with morphology in BE. MATERIALS AND METHODS: A time-bound study was conducted from January 2011 to June 2015. All esophageal biopsies showing histological evidence of columnar epithelium with the presence of goblet cells were included. The cases which showed dysplasia were graded on hematoxylin and eosin stain. Evaluation of p53 immunohistochemistry staining was done on all the cases of BE. Dysplasia was correlated with the expression of p53 using Chi-square value (χ2) and Fischer's exact test wherever appropriate. P < 0.05 was considered to be statistically significant. RESULTS: Of 829 esophageal biopsies received, 119 were endoscopically suspected to be BE, of which 85 cases were confirmed on microscopy. In our study, there were 75 cases negative for dysplasia (88.2%), 8 with low-grade dysplasia (LGD) (9.4%), and two with high-grade dysplasia (HGD) (2.4%). Three cases of BE had associated adenocarcinoma. Immunostaining with p53 done on all the 85 cases showed positive staining in all cases with LGD, one with HGD and two with adenocarcinoma. In the present study, immunostaining with p53 showed 90% sensitivity, 89.3% specificity, positive predictive value of 52.9%, and negative predictive value of 98.5%. CONCLUSION: The technical simplicity, easy availability, and comparatively lower cost enhance the role of p53 as a biomarker in risk stratification for patients with BE.

Diagnostic Pitfalls in Papillary Lesions of the Breast: Experience from a Single Tertiary Care Center.

INTRODUCTION: Papillary neoplasms are a group of lesions that are characterized by presence of papillae supported by fibrovascular cores lined by epithelial cells with or without myoepithelial cell layer. These neoplasms may be benign, atypical or malignant. AIMS: This study was conducted to analyse the clinicopathological characteristics of papillary lesions of the breast. MATERIALS AND METHODS: A retrospective and prospective analysis of 34 cases of papillary lesions received over a period of 7 years from 2009 to 2015 was done. The patient's clinical details were collected from medical archives and the histopathological findings were reviewed. The lesions were classified into benign, atypical and malignant categories. RESULTS: During the study period, there were 34 cases of papillary lesions of breast. The mean age was 58 years. The central quadrant was the most common location (66.6%). The most common presenting complaint was lump (76.5% cases). Papillary lesions presented more commonly as solitary lump (82.4%) rather than multifocal disease. Benign papillary lesions were more common than the atypical and malignant lesions. The most common papillary lesion accounting for 43% of the cases was intraductal papilloma. Malignant lesions accounted for 41.2% cases with intraductal papillary carcinoma and invasive papillary carcinoma constituting 14.7% cases each. CONCLUSION: Diagnosis of papillary carcinoma is challenging and its classification includes different entities that have specific diagnostic criteria. Due to their heterozygosity in morphology with benign, atypical and malignant subtypes, morphological features such as type of fibrovascular core and continuity of myoepithelial layer along with immunohistochemical stains for myoepithelial cells should be considered for proper and accurate diagnosis.

Double non coronary aortic sinuses: an autopsy case finding showing the arterial variation / Senos aórticos dobles, no coronarios: un caso de autopsia que demuestra la variación arterial

We report a case of variant origin of the right coronary artery from the left posterior aortic sinus. This was observed routinely during a medico legal autopsy of a 58 year old male who died in a road traffic accident. Initially it was believed that the right coronary artery was absent since there was no obvious right coronary artery ostium from the anterior aortic sinus. However it was found later that the right coronary ostium was present just beside the left coronary ostium in the left posterior aortic sinus and the right coronary artery was arising from the left posterior aortic sinus. The right coronary artery had an intramural course between the aorta and pulmonary trunk, which is considered as very dangerous and life threatening. We believe that the present case report will be enlightening to the cardiologist and cardiothoracic surgeon. It is also true that the conduction of medico legal autopsies of coronary arteries is important for the medico legal resolution.

Se presenta un caso de variación de origen de la arteria coronaria derecha desde el seno aórtico posterior izquierdo. Esto se observó de forma rutinaria durante una autopsia médico-legal de un hombre de 58 años que murió en un accidente de tránsito. Inicialmente se creía que la arteria coronaria derecha estaba ausente ya que no había un ostium observable desde el seno aórtico anterior. Sin embargo, se descubrió más tarde que el ostium de la arteria coronaria derecha estaba presente justo al lado del ostium de la arteria coronaria izquierda en el seno aórtico posterior izquierdo y la arteria coronaria derecha se originaba del seno aórtico posterior izquierdo. La arteria coronaria derecha presentó un recorrido intramural entre la aorta y el tronco pulmonar, que se considera como muy peligroso y potencialmente mortal. Creemos que el presente trabajo será esclarecedor para el cardiólogo y el cirujano cardiotorácico. También consideramos que el conocimiento de la anatomía de las arterias coronarias es importante durante el desarrollo de la autopsia médico-legal para lograr alcanzar una correcta resolución del proceso medicolegal.

The Prognostic Significance of Neuroendocrine Differentiation in Colorectal Carcinomas: Our Experience.

INTRODUCTION: Neuroendocrine differentiation in colorectal carcinomas, detected using immunohistochemistry and ultrastructural techniques, has been studied as a prognostic marker for invention of targeted therapy. There are a few studies done on this aspect which have shown conflicting results ranging from poor prognosis to no prognostic significance. AIM: The aim of the study was to determine the clinical significance of neuroendocrine differentiation in colorectal carcinomas using immunohistochemical stains such as chromogranin A & synaptophysin in relation to its prognostic significance. MATERIALS AND METHODS: A retrospective study was conducted wherein all the colorectal carcinomas, received in the Department of Pathology, over a period of 3 years, were reviewed. Neuroendocrine markers were done on 53 cases of moderately, poorly and undifferentiated adenocarcinomas. Based on the degree of immunoreactivity for these markers, tumours were divided into group 0, group 1, group 2, group 3 & group 4. Group 0 & 1 were categorized as neuroendocrine differentiation absent & group 2, 3 & 4 as present. Neuroendocrine differentiation was correlated with age, sex, grade, stage, diagnosis & survival. Follow up data of the cases was recorded. RESULTS: Neuroendocrine differentiation was present in 18 cases (33.9%). The degree of immunoreactivity for neuroendocrine markers in present study were; group 0- 58%, 1- 7.5%, 2- 9%, 3- 13% & 4- 11%. The mean age of patients was 54 years with a slight male preponderance {M:F::1.6:1}. Most of the carcinomas with neuroendocrine differentiation belonged to Grade II (61%) & Stage II & III (83%). Neuroendocrine differentiation did not show any significant association with age, sex, location, histological type, grade, stage & survival. CONCLUSION: The above results indicate that the presence of neuroendocrine differentiation cannot be recommended as a prognostic marker in colorectal carcinomas.

MRI sequence and characteristic features in 'giant cell tumor' of clivus.

Giant cell tumours of the clivus are rare. These tumours present in the second and third decades of life and they are slightly more frequent in women than in men. We are presenting a case of a 20 years young patient who came with the complaints of headache, retro-orbital pain and recurrent transient bleeding from the nose since two and half months. MRI of the brain with contrast was done and its features were suggestive of a Giant cell tumour of the clivus. A transnasal endoscopic biopsy was done under general anaesthesia and the histopathology report suggested that the features were of a giant cell tumour. Excision of the mass was done by Transnasal endoscopy. Post operatively, the patient did not recover from the lateral rectus palsy which was there on the right side. The patient was discharged with an advice of a follow up and radiotherapy. Radiation therapy and chemotherapy may be effective as adjuvant treatments. Even though a recurrence usually occurs within 4 years of the initial treatment, these patients will need to be carefully followed for the remainder of their lives.

Value of bone marrow examination in Hodgkin lymphoma: report of three cases with review of literature.

Bone marrow involvement by Hodgkin lymphoma is rare with an average incidence of 10%. However, the incidence of bone marrow involvement has been shown to be less than 1% in patients with clinical stage IA or IIA disease. The involvement of the marrow in a patient with Hodgkin lymphoma represents stage IV disease. We report our experience wherein three cases of marrow involvement were picked up on bone marrow aspirates/ -imprints and confirmed on trephine biopsy. In this paper we wish to highlight the significance of bone marrow examination in the initial diagnosis and staging of even clinically early stage Hodgkin lymphoma. Staging investigations performed at the time of diagnosis for patients with Hodgkin lymphoma are vital for determining the appropriate treatment and prognosis.

Adenomyomatous polyp of the uterus: Report of an autopsy case and review of the literature.

Adenomyomatous polyps of the endometrium are a rare subtype of endometrial polyps. In addition to the usual features of endometrial polyps, they also contain a smooth muscle component. Grossly they appear no different than ordinary endometrial polyps. In the case reported herein, a 23-year-old nulliparous female was killed in a traffic accident. In the course of the medicolegal autopsy, a small pedunculated growth was identified in the fundus of the endometrial cavity. Histologically the mass consisted of endometrial glands intimately mixed with smooth muscle and thick walled blood vessels, consistent with an adenomyomatous polyp. There was no history of tamoxifen use in this individual. To our knowledge this is the first report of post-mortem diagnosis of an adenomyomatous polyp. Furthermore, this is the first report of an individual with this diagnosis younger than the fourth decade. In the medicolegal setting, forensic pathologists are constantly faced with entities that, while they may not have caused death, may serve to educate practitioners about rare lesions. This individual's finding serves as one of those entities. This case reiterates the importance of the autopsy as not only the answer to an individual's death, but as an avenue for the discovery of entities that may have relevance to those who are still living.

Giant cystic thymoma with haemorrhage and necrosis: an unusual case.

Extreme degree of cystic, haemorrhagic and necrotic changes in a thymoma is rare. A 22-year-old male presented with cough, grade 2 dyspnoea, and occasional chest pain for the past six months. Radiological investigations revealed a large cystic lesion in the anterior mediastinum. A benign cystic tumour was suspected. Surgical resection of the tumour was done. Grossly, the almost entirely cystic and haemorrhagic dumb-bell shaped encapsulated tumour showed a subcapsular residual nodule. Histopathological examination was suggestive diagnosis of benign thymoma (World Health Organization [WHO] Type A, medullary type) associated with the rare features of cells with dendritic processes containing melanin pigment seen singly scattered throughout the tumour.

Imprint cytology of pancreatoblastoma: a case report and review of the literature.

Pancreatoblastoma is a rare tumor with approximately 60 cases described in the English literature and only five case reports illustrating the cytologic findings, four by fine-needle aspiration cytology and one by imprint cytology. We herein report the sixth case diagnosed by imprint cytology. Both the cytologic and histopathologic literatures are reviewed, and the pathologic variations observed in our case are also documented.