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%).

Comparative analysis of copy number variations in ulcerative colitis associated and sporadic colorectal neoplasia.

BACKGROUND: The incidence of and mortality from colorectal cancers (CRC) can be reduced by early detection. Currently there is a lack of established markers to detect early neoplastic changes. We aimed to identify the copy number variations (CNVs) and the associated genes which could be potential markers for the detection of neoplasia in both ulcerative colitis-associated neoplasia (UC-CRN) and sporadic colorectal neoplasia (S-CRN). METHODS: We employed array comparative genome hybridization (aCGH) to identify CNVs in tissue samples of UC nonprogressor, progressor and sporadic CRC. Select genes within these CNV regions as a panel of markers were validated using quantitative real time PCR (qRT-PCR) method along with the microsatellite instability (MSI) in an independent cohort of samples. Immunohistochemistry (IHC) analysis was also performed. RESULTS: Integrated analysis showed 10 overlapping CNV regions between UC-Progressor and S-CRN, with the 8q and 12p regions showing greater overlap. The qRT-PCR based panel of MYC, MYCN, CCND1, CCND2, EGFR and FNDC3A was successful in detecting neoplasia with an overall accuracy of 54% in S-CRN compared to that of 29% in UC neoplastic samples. IHC study showed that p53 and CCND1 were significantly overexpressed with an increasing frequency from pre-neoplastic to neoplastic stages. EGFR and AMACR were expressed only in the neoplastic conditions. CONCLUSION: CNVs that are common and unique to both UC-associated and sporadic colorectal neoplasm could be the key players driving carcinogenesis. Comparative analysis of CNVs provides testable driver aberrations but needs further evaluation in larger cohorts of samples. These markers may help in developing more effective neoplasia-detection strategies during screening and surveillance programs.

Cervical cytological abnormalities and human papilloma virus infection in women infected with HIV in Southern India.

AIM: The aim of this study was to examine the association between CD4 count, human papilloma virus (HPV) infection, and the risk of cervical intraepithelial neoplasia among HIV-infected women. METHODS: A cross-sectional study was conducted among 104 HIV-infected women attending an antiretroviral therapy clinic. They underwent Pap smear and cervical HPV DNA testing. RESULTS: The overall prevalence of HPV infection was 57.7%. HPV 16 was the commonest genotype found (38.5%); HPV 16 and 18 put together contributed to 73.3% of HPV infection; 27.5% of HIV-infected women had squamous cell abnormalities. Cervical intraepithelial neoplasia was less likely among women with CD4 count > 500/mm3 (12%) and in those without opportunistic infections (17.8%). The prevalence of high-risk HPV infection was higher in women with high-grade squamous intraepithelial lesions or greater lesions (85.7%) as compared to women with normal cytology (52.1%). CONCLUSION: The high prevalence of HPV infection and cervical intraepithelial neoplasia in HIV-infected women warrants the need for regular Pap smear screening in these women and routine HPV vaccination for adolescents to reduce the burden of cervical cancer in India.

Cutaneous neurocristic hamartoma presenting as cutis verticis gyrata.

Cutaneous neurocristic hamartoma is a rare developmental complex melanocytic lesion of neural crest origin in the dermis and subcutis with diverse histological differentiation including melanocytic, neurosustentacular, and mesenchymal elements. Cutis verticis gyrata is a cerebriform thickening of the scalp manifesting as folds, ridges, or creases. We report a case of cutaneous neurocristic hamartoma of the scalp in a 20-year-old woman presenting as cutis verticis gyrata. Microscopically, the lesion involved the dermis and the subcutis. Dendritic pigmented melanocytes were seen in between the collagen bands. Plexiform islands consisting of cords and palisades of spindled cells were also apparent. Immunohistochemically, HMB-45 positivity was observed in the dendritic melanocytic cells. S-100 protein was positive in dendritic melanocytes and in the Schwannian cells. The stromal cells showed CD34 staining. This lesion is presented because of its rarity, unusual clinical appearance, and resemblance to both a neurocristic hamartoma and large plaque type of blue nevus.

Parasitic colloid cyst: A diagnostic dilemma.

The pathologies of the neck are varied and at times may cause a diagnostic dilemma for the pathologist. In this report, we present a case of a 32-year-old man with a slow-growing nodular swelling in the right neck region, which was diagnosed as a simple colloid cyst arising in a parasitic thyroid nodule. Simple colloid cysts are cysts that develop due to impaired accumulation of thyroglobulin in inactive follicles. Most thyroid-related pathologies occur as midline swellings. However, the present case was unique due to its location with no connection to the thyroid gland. This case report describes the diagnostic process and adds insight into the pathology of a colloid cyst.

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.

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.

A needle in the haystack: An unusual case presentation of ganglioneuroblastoma at a tertiary care center in Coastal Karnataka.

Key Clinical Message: This case report highlights the importance of recognizing and accurately diagnosing ganglioneuroblastoma, an uncommon variant of neuroblastic tumors in children. Ganglioneuroblastomas have diverse clinical and morphological presentations, and histopathological examination is paramount in guiding treatment decisions, especially in cases with ambiguous symptoms. Early detection is crucial, as the prognosis varies significantly based on the subtype and the presence of metastatic disease. Clinicians should maintain a high index of suspicion and utilize radiological examinations to promptly identify and treat these tumors. Abstract: Children are frequently affected by neuroblastic tumors, which grow from the sympathoadrenal lineage of the neural crest during its development. However, intermixed ganglioneuroblastomas are far less common within the same tumor spectrum, the diagnosis of which could become challenging amidst an unusual presentation. In our case report, we present a 4-year-old boy who had complaints of fever and difficulty in walking, with a supra-renal mass on ultrasound, which was diagnosed as ganglioneuroblastoma-intermixed type on histopathological examination. This report aims to contribute to the understanding of the diverse clinical and morphological spectrum of ganglioneuroblastomas and the importance of multidisciplinary collaboration and histopathological examination to enhance decision-making in such ambiguous scenarios.

A Silent Non-thyroidal Adenoma in the Thyroid.

The surgeon needs to assess clinically significant thyroid nodules as they may represent aggressive forms of thyroid cancer or ectopic parathyroid glands. We discuss one such unusual nodule in the thyroid.

Heat exertion precipitating shock and death in a case of previously undiagnosed sickle-cell disease.

Sickle cell disease (SCD) is an autosomal recessive genetic condition characterized by the presence of a mutated form of haemoglobin (HbS). HbS polymerises into long needle-like fibres under low oxygen conditions, leading to the erythrocytes forming sickle shaped red blood cells. With repeated sickling, the red blood cells become irreversibly sickled and trapped within the circulation, and this leads to vaso-occlusive crisis. The patient, a 25-year-old female, previously undiagnosed with SCD, presented with high grade fever, splenomegaly and succumbed due to heat exertion precipitating sickling crisis, multiorgan failure and shock.

Isolated thyroid carcinoma in an ectopic thyroid tissue.

Ectopic thyroid tissue (ETT) is a rare developmental abnormality due to aberrant embryogenesis of the thyroid gland. Although rare (<1%), papillary thyroid carcinoma (PTC) is the most common malignant transformation seen. A 34-year-old man presented with neck nodal swelling, on preoperative evaluation, was found to have PT) in ETT with the normal thyroid gland and nodal metastasis. The patient underwent surgery for PTC along with Sistrunk's procedure and the histopathology revealed ectopic thyroid carcinoma with a normal thyroid and lymph nodal metastasis. Although a rare entity, the possibility of an ectopic thyroid carcinoma should be considered in differentiated cancers with neck nodes in the setting of a normal thyroid gland. Clinical suspicion and radiological imaging would help improve the preoperative diagnosis which in turn alters the management and thereby providing a better outcome to the patient.

Beware the perianal granuloma! A case report.

BACKGROUND: Crohn's disease (CD) can often present initially with extraintestinal manifestations and/or perianal disease. Cytology of such a lesion helps arrive at the diagnosis. CASE: A 27-year-old woman presented with recurrent, painful, discharging perianal lesions. On examination, multiple perianal abscesses, sinuses, skin tags and healed scars were noted. Fine needle aspiration cytology (FNAC) of the perianal lesions performed as a first line investigation revealed epithelioid granulomas in a suppurative background. The possibility of tuberculosis vs. extraintestinal manifestation of CD was considered. Endoscopic studies revealed involvement of distal ileum and the entire colon by deep, serpiginous ulcers, internal fistulae and a distorted ileocecal valve. Biopsy of the intestinal lesions revealed chronic inflammation, aphthous ulcers and microgranulomas, favoring a diagnosis of CD. CONCLUSION: A granulomatous lesion in any location arouses the clinical suspicion of tuberculosis, given its prevalence in the Indian subcontinent. In view of the increasing incidence of CD in our setting, the finding of a perianal, granulomatous lesion on cytology should prompt a workup for CD in addition to the more common granulomatous counterpart, tuberculosis. Perianal aspiration is an underused diagnostic procedure that can help in narrowing the differential diagnostic possibilities.

Assessment of p16 and Ki67 Immunohistochemistry Expression in Squamous Intraepithelial Lesion with Cytohistomorphological Correlation.

BACKGROUND & OBJECTIVE: Cervical cancer is the most common cancer in women worldwide with high mortality, necessitating quicker diagnostic methods. We wish to enhance the existing cervical biopsies of Squamous Intraepithelial Lesions (SIL) using p16 and Ki67 as surrogate markers to assess correlation between its positivity and histological grade of the lesion. METHODS: Analysis of p16 and Ki67 expression was done on 31 histopathologically diagnosed cases of SILs. Positive expression of p16 was assessed based on a scoring system and compared with histology and cytology. Ki67 expression was studied and the correlation was observed with degree of dysplasia. Twenty cases of chronic cervicitis was assigned to the control group for comparison. RESULTS: Cases of HSIL showed greater expression of p16 as compared to LSIL. Sensitivity of p16 for HSIL was higher than that for LSIL. The specificity for HSIL and LSIL was 100%. Ki67 expression correlated well with the degree and level of dysplasia with a significant P-value of 0.002. CONCLUSION: p16 and Ki67 positivity of SILs should point towards further evaluation. The expressions of p16 and Ki67 are useful markers for confirmation of SILs and in predicting HPV infection which can be further confirmed by HPV DNA testing.

T-cell lymphomas in a tertiary care center of Mangalore.

BACKGROUND: The clinicomorphology and immunohistochemical features of T-cell lymphomas have been documented. AIM: The aim of the study was to evaluate the spectrum of clincopathological features of T-cell lymphoma with immunohistochemistry correlation in a tertiary care center. MATERIALS AND METHODS: The present study was conducted on 19 biopsy specimens received from the Department of Pathology, Kasturba Medical College, from referral hospitals of Mangalore city. Cases of nodal and extranodal T-cell lymphomas diagnosed between January 2012 and December 2015 were selected with evaluation of clinical data, histomorphological features, and immunophenotyping. Appropriate panel of antibodies was chosen after morphological evaluation of the cases. RESULTS: Of the 19 cases of T-cell lymphomas, 14 were nodal disease and 5 were extranodal disease. Among the nodal lymphomas, five were primary peripheral T-cell lymphoma-not otherwise specified (PTCL-NOS), four were cases of lymphoblastic lymphoma, three were cases of angioimmunoblastic T-cell lymphomas, and two were cases of anaplastic large-cell lymphoma anaplastic lymphoma kinase (ALK) negative. In extranodal disease, two were mycosis fungoides of skin, one case each of subcutaneous panniculitis-like T-cell lymphoma, T-cell lymphoblastic lymphoma of tonsil, and T-cell lymphoma of the stomach. CONCLUSIONS: The diagnosis and subclassification of PTCLs is necessary for therapeutic and prognostic purposes.

Xanthomatous hypophysitis: A rare case report with review of literature.

Hypophysitis is classified into primary and secondary. Xanthomatous hypophysitis is one of the rare types of primary hypophysitis. A 55-year-old female presented with headache, vomiting, and blurring of vision. She also had endocrine dysfunction in the form of low serum T3, T4, and low cortisol levels. MRI scan showed a sellar expansile lesion suggestive of pituitary macroadenoma. Microscopy showed pituitary tissue replaced by inflammatory infiltrate made up of foamy histiocytes arranged in sheets along with lymphoplasmacytic infiltrate. Interspersed areas of fibrosis, hyalinization, few congested and sclerosed blood vessels were seen. Compressed residual pituitary tissue was identified at the periphery. Xanthomatous hypophysitis is a rare entity which can mimic as pituitary adenoma both clinically and radiologically. Accurate diagnosis at an early stage with postsurgical steroid therapy may help to prevent permanent pituitary damage.

Clear cell carcinoma of breast lipid-rich variant.

Clear cell breast carcinomas are one of the rare types of invasive carcinoma of the breast. Among them, lipid-rich variant is still rare comprising <1%. The tumor derives its name from the intracytoplasmic neutral lipid that gives the cytoplasm a vacuolated and foamy appearance. These tumors are usually hormone receptors negative and Her-2 Neu positive. Here, we report a case of lipid-rich breast carcinoma which showed hormone receptor positivity and Her-2 Neu negative.

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.

A Study of Pap Smears in HIV-Positive and HIV-Negative Women from a Tertiary Care Center in South India.

OBJECTIVES: The aim of this work was to study the spectrum of epithelial abnormalities on Pap smears of HIV-positive women categorized as per the Bethesda System of Reporting Cervical Cytology, to correlate them with CD4 lymphocyte counts, and to compare them with the spectrum of abnormalities seen in a HIV-negative control group. Study Design and Methodology: The present study was a 6-year retrospective study conducted in the Department of Pathology at Kasturba Medical College, Mangalore, which included 150 Pap smears from HIV-positive and HIV-negative women, respectively. The Pap-stained slides of the cases were retrieved and studied. The data collected were tabulated and analyzed. A statistical study was performed using SPSS software. The χ2 test was used to analyze the data and a p value < 0.05 was considered to be significant. RESULTS: Pap smear abnormalities were twice as high in HIV-infected women (12%) as compared with HIV-negative women (6%; p = 0.006, RR = 2). Negative for intraepithelial lesion/malignancy was the most common finding (88%), which was further subdivided into inflammatory, atrophic smear, non-specific, candidiasis, and bacterial vaginitis groups. The percentage of epithelial abnormalities was 12%, including: atypical squamous cells of undetermined significance, 5.55%; atypical squamous cells, cannot exclude HSIL, 16.66%; low-grade squamous intraepithelial lesion, 5.55%; high-grade squamous intraepithelial lesion (HSIL), 61.11%, and squamous cell carcinoma, 11.11%. The highest incidence of intraepithelial lesions in HIV-positive females was in the age group of 34-49 years. CD4 cell counts fell in the range of 200-500 cells/mm3 in most of the HIV-positive patients (68.75%), but was not found to be statistically significant. CONCLUSION: Routine Pap smear examination is advocated in women with HIV as the prevalence of epithelial cell abnormalities was found to be 12%, which was twice as high as compared to the HIV-negative control group. Although there was no correlation of epithelial cell abnormalities with CD4 counts, a higher rate of the cases with epithelial abnormalities were observed to have CD4 cell counts of 200-500 cells/mm3.

Wegener's granulomatosis mimicking paraneoplastic syndrome.

Wegener's granulomatosis is a distinct clinico-pathological entity characterised by a triad of upper and lower respiratory disease and renal involvement, although atypical presentations can be seen. These patients characteristically have small vessel vasculitis and or granulomatous vasculitis and are usually anti-neutrophilic cytoplasmic antibody (ANCA) positive. We present a case of Wegener's granulomatosis that clinically mimicked a lung neoplasm with a paraneoplastic syndrome. Biopsy and histopathological evaluation of a readily accessible subcutaneous nodule showed small vessel vasculitis. Correlation with clinical data and ANCA positivity led to a definite diagnosis.