The elusive extremities: a case of extramammary Paget disease.

Extramammary Paget disease is a rare dermatological condition resembling Paget disease that occurs most commonly in the anogenital area and axilla. We present the case of an elderly male who had come with complaints of an itchy, erythematous and raised lesion in the perianal region for 3 months that did not respond to antifungals. A biopsy was taken from the lesion site and the diagnosis was confirmed by histopathological examination. It is important to be aware of conditions like extramammary Paget disease when an elderly individual presents with a non-specific pruritic lesion in the perianal area that is non-responsive to treatment; the diagnosis of which can be made only by doing a biopsy from the concerned site. This highlights the importance of histopathological examination in such ambiguous cases.

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.

Primary neuroendocrine breast cancer-an unusual occurrence.

Primary breast neuroendocrine neoplasms (BNENs) are a rare form of breast cancer, accounting for less than 0.1% of all breast malignancies. These neoplasms have a similar clinical presentation as conventional breast carcinomas, differing mainly in their histopathology and expression of neuroendocrine (NE) markers, chromogranin and synaptophysin. Owing to their rarity, current knowledge of these tumours comes mainly from corroborative case reports or retrospective case series. There is hence a lack of randomised data on the treatment of these entities and current protocol suggests similar treatment as that of conventional breast carcinomas. We report the case of a 48-year-old with a breast mass, which on further work-up was diagnosed as locally advanced carcinoma breast, that required a mastectomy and axillary node dissection on the same side and revealed NE differentiation on histopathological examination. Hence, immunohistochemical staining was indicated which confirmed NE differentiation. We discuss the current knowledge on incidence, demographics, diagnosis, histopathological and staining characteristics, prognostic factors and treatment modalities of BNENs.

The role of tumor-educated platelets in ovarian cancer: A comprehensive review and update.

Platelets have recently surfaced as critical players in cancer metastasis and the local and systemic responses to tumor growth. The emerging concept of "Tumor-educated platelets (TEPs)" comprises the exchange of biomolecules between tumor cells and platelets, thereby leading to the "education" of platelets. Increased platelet numbers have long been associated with cancer patients' tumor metastasis and poor clinical prognosis. However, it is very recently that researchers have delved deeper into the tumor-microenvironment and probed the mechanism of interactions between tumor cells and platelets. Designing strategies to target the TEPs and the communications between platelets and tumor cells can prove to be a promising breakthrough in cancer therapy. Through this review, we aim to analyze the recent developments in this field and discuss the characteristics of TEPs, focusing on ovarian cancer-associated TEPs and their characteristics, the interplay between ovarian cancer-associated TEPs and cancer cells, and the purview of TEP-targeted cancer diagnosis and therapy, including platelet biomarkers and inhibitors.

Immunohistochemical expression of androgen receptors in urothelial carcinoma of urinary bladder. Is it significant? Experience from coastal India.

BACKGROUND: Bladder carcinoma (BC) ranks second among the genitourinary cancers worldwide. Influence of androgens and expression of androgen receptors in neoplasms are recent findings which were implicated in the development of BC. We aimed to study androgen receptor (AR) expression in bladder urothelial neoplasms and correlate its expression with grade and stage of the tumor. METHODS: Immunohistochemistry (IHC) was done on samples collected in a tertiary care hospital over one year consisting of 71 urothelial BC and 20 non-neoplastic urothelial conditions. Two pathologists graded the IHC and nuclear staining was considered as positive expression. RESULTS: AR was expressed in 23.9% (17/71) of bladder urothelial neoplasms. AR was expressed in 25.7% and 22.3% of high and low-grade tumors and 25% and 22.3% of non muscle-invasive and muscle-invasive BC. AR expression had no significant correlation with gender, age (> 50 years), muscle invasion or grade. AR expression was significantly absent in non-neoplastic conditions (p = 0.018). CONCLUSIONS: AR has varied expression in BC and it is relatively lower in this study population.

Tumor Budding Assessment with Cytokeratin and Its Significance in Laryngeal Squamous Cell Carcinomas.

There is a need for novel prognostic parameters in assessing laryngeal squamous cell carcinoma (LSCC). Tumor budding is an instrumental parameter, which has hardly been studied before in this organ. This study aimed to assess tumor budding in LSCCs with routine hematoxylin and eosin (H&E) stain as well as cytokeratin (CK) immunohistochemistry (IHC). Objectives were to compare the effectiveness of both these methods to assess tumor budding, to investigate the association of tumor budding and clinicopathologic features, and to determine the prognostic significance of tumor budding in LSCCs. Fifty laryngectomy specimens were included. Tumor budding was counted (20x) on slides stained with IHC-CK, and highest count per slide was noted. The cases were classified as positive (> 1 buds) or negative (no buds present). The budding index was categorized as low (< 5 buds) or high (> 5 buds). Tumor budding on H&E was absent, low and high grade in 28%, 30% and 42% cases respectively, when compared to CK-IHC in 17%, 24% and 59% of cases, respectively. Presence of lymphoplasmacytic infiltration significantly correlated with tumor budding and higher grade. Transglottic location of tumor and pT stage was associated with high budding. Presence of lymphoplasmacytic infiltrate significantly correlated with worse prognosis. Tumor budding, an easily assessable, inexpensive histopathologic parameter has seldom been studied in LSCCs. Presence of lymphoplasmacytic infiltrate in routine preoperative biopsy reporting could be useful in prognostication. CK-IHC is helpful to detect especially cases with low-grade tumor budding.

Histopathological Study of Benign Tumours of the Larynx: A Descriptive Study in Coastal Karnataka.

A laryngoscopically benign lesion with minimal hoarseness may turn out to be mimickers of malignancy or malignancy itself. Histopathological study is mandatory in such cases to rule out malignancy. A descriptive study of histopathological and laryngoscopic findings of benign laryngeal lesions were studies over a period of 4.5 years. Among the thirty-six patients studied, the mean age of the patients was 42 years. The most common presenting complaint was hoarseness of voice seen in 87.5% of cases. Twelve cases of vocal cord polyps were diagnosed based on clinical, laryngoscopical and histopathological features. Seven cases of vocal cord nodules, presenting with hoarseness of voice and laryngoscopic finding of a small nodular growth over the cord. Nine cases of laryngeal papillomas and papillomatosis showed branching papillae, lined by squamous epithelium with fibrovascular cores. A single case of amyloidosis and four cases of granulomatous lesions suggestive of tuberculosis were studied. One case each of rhabdomyoma and granular cell tumour was reported and confirmed by immunohistochemistry. Rare benign tumours and tumour-like lesions mimicking malignancy on laryngoscopy need histopathological evaluation. It is mandatory to study excised biopsies of the larynx as grossly similar lesions can vary from non-neoplastic to frankly malignant.

Semantic segmentation of low magnification effusion cytology images: A semi-supervised approach.

Cytopathologists examine microscopic images obtained at various magnifications to identify malignancy in effusions. They locate the malignant cell clusters at a low magnification and then zoom in to investigate cell-level features at a high magnification. This study predicts the malignancy at low magnification levels such as 4X and 10X in effusion cytology images to reduce scanning time. However, the most challenging problem is annotating the low magnification images, particularly the 4X images. This paper extends two semi-supervised learning (SSL) models, MixMatch and FixMatch, for semantic segmentation. The original FixMatch and MixMatch algorithms are designed for classification tasks. While performing image augmentation, the generated pseudo labels are spatially altered. We introduce reverse augmentation to compensate for the effect of the spatial alterations. The extended models are trained using labelled 10X and unlabelled 4X images. The average F-score of benign and malignant pixels on the predictions of 4X images is improved approximately by 9% for both Extended MixMatch and Extended FixMatch respectively compared with the baseline model. In the Extended MixMatch, 62% sub-regions of low magnification images are eliminated from scanning at a higher magnification, thereby saving scanning time.

Efficacy and Validity of Image-Guided Percutaneous Fine Needle Aspiration and Core Biopsy of Liver Pathologies: Saga of Focal Hepatic Lesions from the Nodule to the Needle to the Slide.

CONTEXT: Radiology and pathology are pivotal tools in the investigational artillery for management of wide spectrum of hepatic lesions and early detection is of a paramount importance. AIMS: The study aimed at analyzing the efficacy, comparative yield and validity of image-guided aspiration cytology (FNA)/core biopsy (CB) in focal hepatic lesions. SETTINGS AND DESIGN: A retrospective hospital-based study was conducted in departments of Pathology and Radiology and Imaging of a tertiary care center. MATERIALS AND METHODS: Cases of focal hepatic lesions that underwent percutaneous image guided-FNA reported (2011-2018) were analyzed. Cytological-histopathological correlation was performed where available. FNA diagnoses were divided into four categories-positive for malignancy (group 1), atypical (group 2), negative for malignancy (group 3), and non-diagnostic (group 4). STATISTICAL ANALYSIS USED: Categorical data was depicted in the form of frequencies and proportions. Validity of percutaneous image-guided FNA diagnosis was collated with the final diagnosis and results were analyzed. RESULTS: A total of 338 FNA of focal hepatic lesions were reported in which 217 (68.2%) cases in group 1; 21 (6.2%) in group 2; 58 (17.2%) in group 3 and 42 (12.4%) in group 4. CB correlation was available in 123 cases. Based on clinical, radiological and pathological findings, conclusive final diagnoses were obtained and the cases were regrouped [malignant cases-245, benign lesions-57 and uncertain lesions-36]. Metastasis was the most common malignancy (175/245; 71.4%). Sensitivity, specificity, and overall diagnostic accuracy of FNA to categorize the lesion as benign or malignant were 96.94%, 100% and 97.51%, respectively. However, the cytology-histopathology correlation revealed discordance of subtyping the lesion in 20% of cases and sensitivity and specificity reduced to 80% and 50% respectively in rendering the specific diagnosis. CONCLUSIONS: Percutaneous image-guided FNA is a sensitive and specific tool with high diagnostic accuracy in evaluating focal hepatic lesions. The study highlights the pre-eminence of interventional radiology and cytology in the care of patients with liver lesions.

Shine like gold and sparkle like glitter: Three cases of lipoid pneumonia.

Lipoid pneumonia (LP) is an unwonted, mostly asymptomatic entity which has no classical radiological appearance. It can be endogenous or exogenous depending upon the type of exposure or underlying milieu. It simulates a number of infective and malignant respiratory conditions and can go undiagnosed or delayed leading to morbidity and mortality. We put forward three cases that initially presented as classical pneumonia, but on further assessment and investigations were diagnosed to be LP. All the three cases manifested with symptoms of fever, productive cough and breathlessness. Chest Xray and CT scan were indicative of consolidation. Bronchoalveolar lavage (BAL) evinced lipid laden macrophages that stained positive with fat stains (Sudan IV and Oil Red O). Two cases were endogenous and one was exogenous type. LP, owing to its nonspecific clinical presentation and radiographic signs, needs a high index of suspicion, and a detailed clinical history for accurate diagnosis. Corroboration of lipid laden alveolar macrophages in BAL is the crux to the diagnosis. Hence, clinicians should be cognizant of this condition and rule out LP in cases of non-resolving pneumonia in an appropriate clinical context.

Discriminant value of automated leucocyte VCS parameters in the detection of tropical infections.

INTRODUCTION: In India, infectious diseases are a leading treatable cause of morbidity and mortality. Mangalore being endemic to many vector-borne diseases, their incidence is known to show seasonal variations with sharp increase during monsoon. Leucocytes have substantial role in the immunological pathogenesis of infections. METHODS: The present series was a hospital-based cross-sectional study performed in a tertiary care hospital for a period of three months from June-August wherein the cell population data of cases of malaria, dengue, leptospirosis, typhoid and rickettsial infections along with equal number of healthy controls were collected and analysed. Effectiveness of leucocyte-related volume (V), conductivity (C) and scatter (S) parameters by Coulter®DXH800 haematology analyser in predicting these infections was appraised. RESULTS: A total of 324 cases comprising of malaria (50%), dengue (30.9%), leptospirosis (13.9%), typhoid (4.0%) and rickettsial infections (1.2%) were included. There was statistically significant differences (P < 0.05) in the mean values of complete blood count parameters-haemoglobin, total leucocyte count, red blood cell count, haematocrit, red cell distribution width, differential leucocyte count, platelet count and plateletcrit between cases and controls and also between specific infections. The mean volumes of neutrophil, monocyte and lymphocyte were considerably increased in malaria and dengue fever compared to leptospirosis, typhoid and rickettsial infections. VCS parameters were the least altered in typhoid fever, except for a strikingly high conductivity and scatter of eosinophils. CONCLUSIONS: Haematological analysis is a part of routine evaluation of any case of febrile illness. This study showed that there are specific alterations in VCS parameters in different types of infections such as malaria, dengue, leptospira, typhoid and rickettsia, the information and analysis of which comes without any additional cost.

Deep Learning Model based Ki-67 Index estimation with Automatically Labelled Data.

Ki-67 labelling index is a biomarker which is used across the world to predict the aggressiveness of cancer. To compute the Ki-67 index, pathologists normally count the tumour nuclei from the slide images manually; hence it is timeconsuming and is subject to inter pathologist variability. With the development of image processing and machine learning, many methods have been introduced for automatic Ki-67 estimation. But most of them require manual annotations and are restricted to one type of cancer. In this work, we propose a pooled Otsu's method to generate labels and train a semantic segmentation deep neural network (DNN). The output is postprocessed to find the Ki-67 index. Evaluation of two different types of cancer (bladder and breast cancer) results in a mean absolute error of 3.52%. The performance of the DNN trained with automatic labels is better than DNN trained with ground truth by an absolute value of 1.25%.

Diagnostic dilemma of a thumb swelling: An unpropitious turn of events.

Benign and malignant bone tumors arise in small bones of the hands and feet. Nevertheless, secondary deposits at these sites are extremely rare. We report a peculiar case of an adult man who presented with thumb swelling, which was later discovered to be a metastasis from renal cell carcinoma. Such cases have a sinister prognosis with a survival rate of 6-12 months from the time of diagnosis. We intend to discuss the diagnostic dilemma and treatment of acrometastases.

Schwannoma: An uncommon dweller in the adrenal gland.

An elderly adult woman presented with upper abdominal pain to the urology department. Imaging studies revealed a right adrenal lesion with central necrosis, abutting the large vessels and suggestive of malignancy. Histopathology showed an encapsulated spindle cell tumor with marked nuclear atypia, cystic change, and hemorrhage. S100 immunomarker was strongly and diffusely positive. Final diagnosis was ancient schwannoma with secondary change. Schwannomas are rare in the adrenal gland, with <50 cases reported in the literature. These incidentally detected nonfunctional adrenal tumors need confirmation with histopathology and ancillary studies.

Granuloma in marrow with lurking "Leuk": Two happenstances.

Granulomas are described very rarely in marrow biopsies. They have hardly been reported in association with acute lymphoblastic leukemia. We herein report two cases of ALL associated with granulomas each at different stage of their clinical course that led to a diagnostic and therapeutic dilemma. First case was of a 42-year-old woman diagnosed with tuberculosis who presented with bleeding gums during anti-tubercular therapy. In the second scenario, a 51-year-old man presented with pyrexia of unknown origin and splenomegaly who was put on a trial of ATT. Peripheral smear showed only 1-2% abnormal cells, however, bone marrow aspiration and flow cytometry pattern was diagnostic of ALL. Both the patients received chemotherapy and have been on remission so far. These case scenarios put forward a relevant question on this rare coexistence, as the implications on management are manifold.

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.

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%).

Is MPV a Predictive Marker for Neonatal Sepsis? A Pilot Study.

Neonatal sepsis (NS) continues to be a diagnostic challenge and a prime cause of mortality. Forage for a lucid, cost-effective yet highly sensitive and specific marker in diagnosing this entity is an incessant task. This study aimed to evaluate the predictive value of mean platelet volume (MPV) in diagnosing NS. Neonates diagnosed with sepsis from January 2016 to March 2016 were included in the study. The subjects were stratified into the following: (i) culture-proven sepsis (group I); (ii) culture-negative clinical sepsis (group II); and (iii) control group (group III). Several hematologic markers such as hemoglobin, total leukocyte count, platelet count, MPV, plateletcrit, platelet distribution width, immature-to-mature neutrophil ratio, toxic change, serum urea, bilirubin, and C-reactive protein were analyzed. The results were compared among the groups, and their efficacy in diagnosing NS was appraised. The study involved 210 neonates, of which, groups I, II, and III constituted 64, 75, and 71 cases, respectively. The mean MPV among groups I, II, and III was 9.56, 8.86, and 8.58 fL, respectively (P<0.05). Strikingly higher values of platelet count, immature-to-mature neutrophil ratio, MPV, plateletcrit, and C-reactive protein were found in group I in contrast to those in groups II and III (P<0.05). The baseline MPV of patients with culture-proven sepsis was comparatively higher than controls and was found to be statistically significant. Hence, MPV can be a simple, economical, and specific predictor of NS.