Expression of stathmin in oral squamous cell carcinoma and its correlation with tumour proliferation.

Background: Stathmin is a member of microtubule-associated protein. Inhibition of Stathmin expression can interfere with tumour progression and also alter the sensitivity of tumour cells to microtubule-targeting agents. Thus, it could be a potential therapeutic target for planning new treatment strategies. Objective: To study expression of Stathmin in different histological grades of oral squamous cell carcinoma (OSCC) and its correlation with Ki67 index. Materials and Methods: This study was an observational retrospective and prospective study conducted during a period of two and half years from January 2015 to June 2017 at ESI-PGIMSR Maniktala, Kolkata where 52 cases of OSCC were studied. Haematoxylin and eosin sections were reviewed and representative paraffin blocks were selected. Immunostains were performed using antibody clones for Stathmin and Ki67. For Stathmin scoring, Segersten scoring system was applied. Statistical analysis was done by Graph Pad Prism using Krusher Wallis Test and one-way ANOVA test. Spearman's coefficient was used to establish corelation between Ki 67 and Stathmin overexpression. Results: In this study, it is found that strong Stathmin expression score (4-9) was detected mostly (82.35%) in moderately differentiated (MD) OSCC and poorly differentiated (PD) OSCC (100%), whereas in contrast, 60% of well-differentiated OSCC showed negative-to-weak Stathmin score (1-3). Mean Ki67-labelling index for well-differentiated carcinoma was 32.37%, for moderately differentiated carcinoma was 60.89, and poorly differentiated carcinoma was 86.15%, which demonstrated increased tumour cell proliferation with progression of histological grades of OSCC. Conclusion: Stathmin expression was higher in MD OSCC to PD OSCC compared to well-differentiated carcinoma and its overexpression was significantly correlated with Ki67 index. Thus, Stathmin is overexpressed in higher grades and is correlated with high proliferation of tumour with a potential role as therapeutic target.

Tumor-Associated CD19+CD39- B Regulatory Cells Deregulate Class-Switch Recombination to Suppress Antibody Responses.

B cells are an essential component of humoral immunity. Their primary function is to mount antigen-specific antibody responses to eliminate pathogens. Despite an increase in B-cell number, we found that serum-IgG levels were low in patients with breast cancer. To solve this conundrum, we used high-dimensional flow cytometry to analyze the heterogeneity of B-cell populations and identified a tumor-specific CD19+CD24hiCD38hi IL10-producing B regulatory (Breg)-cell subset. Although IL10 is a Breg-cell marker, being an intracellular protein, it is of limited value for Breg-cell isolation. Highly expressed Breg-cell surface proteins CD24 and CD38 also impede the isolation of viable Breg cells. These are hurdles that limit understanding of Breg-cell functions. Our transcriptomic analysis identified, CD39-negativity as an exclusive, sorting-friendly surface marker for tumor-associated Breg cells. We found that the identified CD19+CD39‒IL10+ B-cell population was suppressive in nature as it limited T helper-cell proliferation, type-1 cytokine production, and T effector-cell survival, and augmented CD4+FOXP3+ regulatory T-cell generation. These tumor-associated Breg cells were also found to restrict autologous T follicular helper-cell expansion and IL21 secretion, thereby inhibiting germinal transcript formation and activation-induced cytidine deaminase expression involved in H-chain class-switch recombination (CSR). This isotype-switching abnormality was shown to hinder B-cell differentiation into class-switched memory B cells and subsequent high-affinity antibody-producing plasma B cells, which collectively led to the dampening of IgG-mediated antibody responses in patients with cancer. As low IgG is associated with poor prognosis in patients with cancer, Breg-cell depletion could be a promising future therapy for boosting plasma B cell-mediated antibody responses.

GFI1/HDAC1-axis differentially regulates immunosuppressive CD73 in human tumor-associated FOXP3+ Th17 and inflammation-linked Th17 cells.

Plasticity between Th17 and Treg cells is regarded as a crucial determinant of tumor-associated immunosuppression. Classically Th17 cells mediate inflammatory responses through production of cytokine IL17. Recently, Th17 cells have also been shown to acquire suppressive phenotypes in tumor microenvironment. However, the mechanism by which they acquire such immunosuppressive properties is still elusive. Here, we report that in tumor microenvironment Th17 cell acquires immunosuppressive properties by expressing Treg lineage-specific transcription factor FOXP3 and ectonucleotidase CD73. We designate this cell as Th17reg cell and perceive that such immunosuppressive property is dependent on CD73. It was observed that in classical Th17 cell, GFI1 recruits HDAC1 to change the euchromatin into tightly-packed heterochromatin at the proximal-promoter region of CD73 to repress its expression. Whereas in Th17reg cells GFI1 cannot get access to CD73-promoter due to heterochromatin state at its binding site and, thus, cannot recruit HDAC1, failing to suppress the expression of CD73.

Significance of HER2 and Ki-67 in Preneoplastic Lesions and Carcinoma of Gallbladder.

BACKGROUND: HER2 is an oncoprotein which is overexpressed in several cancers including breast and stomach. Several studies have shown that HER2 is overexpressed in gallbladder cancer and in precancerous lesions. The present study was undertaken to assess pattern and level of expression of HER2 in metaplasia, dysplasia, and different stages of gallbladder carcinoma, which would determine its suitability as a prognostic biomarker in neoplastic transformation of gallbladder epithelium. The study was also aimed at to find the significance of Ki-67 index in these lesions. METHODS AND MATERIALS: One hundred and twenty-eight patients who underwent cholecystectomy comprised the study group. Among them, 108 (84.4%) specimens showing metaplasia, dysplasia, and carcinoma on routine histopathology were considered as cases and 20 (15.6%) specimens of chronic cholecystitis having non-metaplastic mucosa were considered as control. Immunohistochemistry (IHC) was performed for HER2 and Ki-67. For HER2 interpretation ASCO/CAP guideline for breast cancer was followed. Chi-square test was used to find out the significance of HER2 expression in dysplasia/metaplasia/carcinoma. The ANOVA and Tukey-Kramer Multiple Comparisons Test were used for determining the association of Ki-67 with malignant transformation. RESULTS AND CONCLUSIONS: Overexpression of HER2 was observed in 48% (n = 12) of adenocarcinomas, 58% (n = 7) of high-grade dysplasia, 47% (n = 8) of low-grade dysplasia, and 74% (n = 25) of intestinal metaplasia. Ki-67 index increases in a non-linear fashion as the precursor lesions progress toward malignancy. In the future, these markers might be used as a prognostic biomarker for gallbladder carcinoma and its precursor lesions and it might become a valid indication for targeted therapies for gallbladder cancer.

Visceral leishmaniasis with pleural effusion in an immunocompetent patient.

Visceral leishmaniasis (VL) is usually characterized by splenomegaly, pallor and fever. Pleural effusion is an uncommon feature of this disease, which is encountered in immunocompromised patients. Here, we report a case of VL with pleural effusion in an immunocompetent patient. Pulmonary symptoms in VL are usually related to bacterial lung infection, vagal nerve compression by splenomegaly, and hypoalbuminaemia with mild pulmonary edema. Our patient presented with cough and chest pain. The clinical features of this case were baffling since they mimicked that of pulmonary tuberculosis. This case report emphasizes the need to recognize the diverse nature of presentation of this curable yet fatal infectious disease.

Fine needle aspiration cytology of ovarian tumors with histological correlation.

BACKGROUND: Till today, there has been some hesitation to accept the role of fine needle aspiration cytology (FNAC) in pelvic mass. We have tried to study the role of ultrasonography (USG) and computed tomography (CT) guided FNAC as diagnostic and supportive investigation for ovarian tumors. AIM: To evaluate the current status of image-directed percutaneous aspiration of ovarian neoplasm for the purpose of early detection of malignancy. MATERIALS AND METHODS: Seventy-four fine needle aspirations of ovarian neoplasms were performed between January 2007 and December 2008 by transabdominal approach under USG and CT guidance and correlated with histopathological findings and tumor markers. RESULTS: A total of 47 (63.5%) cases were assessed as malignant and 21 (28.3%) as benign and 6 (8.1%) as inconclusive. The neoplastic lesions were categorized as per World Health Organization (WHO) classification. CONCLUSION: With the availability of modern techniques, USG and CT guided FNAC can be an optimum modality for the diagnosis of primary and metastatic ovarian neoplasms and evaluation of recurrent malignant tumors, which has great impact on patient management consequently.

Unilateral retinal dysplasia clinically mimicking retinoblastoma.

Retinal dysplasia is a rare non-neoplastic congenital disorder characterized by aberrant differentiation of the retina with formation of abnormal tubular and rosette-like structure. Clinically, the lesion presents with leukocoria and mimics a retinoblastoma. One such case is described that occurred unilaterally in a 9-month-old boy.

Occult micrometastasis to bone marrow in early lung cancer: a clinicopathologic study from West Bengal, India.

Although bone marrow micrometastasis may remain silent, its detection changes the staging and management of lung cancer. In the present study conducted in West Bengal, India, 74 diagnosed bronchogenic carcinoma cases (28 squamous cell carcinomas, 20 adenocarcinomas, 9 small cell carcinomas, 4 large cell carcinomas, 13 unclassified) in early stages (stage I, II and IIIA) were included. Complete hemograms, bone marrow aspiration and cell blocks of aspirated material, trephine biopsy were done for detection of micrometastasis. Overall micrometastases in bone marrow were noted in 17 cases (23.0%). We detected marrow metastasis in 44.4% cases of small cell carcinomas and 21.2% cases of non small cell lung cancer (50% of large cell carcinomas, 20% of adenocarcinomas, 17.9% of squamous cell carcinomas) and 15.4% cases of unclassified carcinoma. We found a statistically significant correlation between marrow metastasis and low platelet count (P=0.0001) and high ESR (P=0.0003), but no significant correlation with hemoglobin percentage (P=0.36), total leukocyte count (P=0.58) and eosinophil count (P=0.44). A definite correlation noted between micrometastasis with the clinical stage (no case in Stage I, 12.5% in Stage II, 30.4% in Stage IIIA patients). We emphasize that detection of micrometastasis is essential particularly in non small cell cancers, where treatment with curative intent is planned, which can be suitably done by morphological study of bone marrow aspirate and biopsy in countries like India.

Extraovarian granulosa cell tumor.

Extraovarian granulosa cell tumor (GCT) is a very uncommon tumor, assumed to arise from the ectopic gonadal tissue along the embryonal route of the genital ridge. One such rare case of extraovarian GCT was encountered in a 58-year-old female who presented with a large intraabdominal lump. Computerized tomography revealed one large retroperitoneal mass measuring 15 cm x 16 cm and another mesenteric mass of 8 cm x 5 cm size. The patient had a history of hysterectomy with bilateral salpingooophorectomy 20 years ago for uterine leiomyoma. Ultrasonography-guided aspiration smears revealed cytological features suggestive of GCT. Histopathological examination of the excised masses showed features of adult-type GCT. Because metastatic epithelial tumors, particularly from the ovaries, may show identical morphology, immunostains for inhibin and epithelial membrane antigen (EMA) were performed. The tumor showed positivity for inhibin while EMA was negative thus confirming the diagnosis of GCT. As this patient had no previous history of GCT and was oophorectomized 20 years ago, the tumor was considered as extraovarian. A diagnosis of extraovarian GCT should be carried out after excluding any previous history of GCT of the ovary. Immunostains help to differentiate GCTs from other neoplasms.

Childhood acute leukemia in West Bengal, India with an emphasis on uncommon clinical features.

Leukemias are the commonest childhood malignancy in West Bengal. This study was undertaken on 75 children at NRS Medical College, West Bengal to determine the distribution of signs and symptoms of leukemia and to identify unusual clinical features. After obtaining clinical history, physical examination, hematological and radiological investigations were performed. Acute lymphoblastic leukaemia (ALL, 72%) was the commonest followed by acute myeloid leukaemia (AML, 18.7%). Common symptoms and signs were fever (85.3%), pallor (64%), hepatomegaly (72%), splenomegaly (60%) and lymphadenopathy (50.7%). The uncommon signs and symptoms were abdominal pain (9.3%), joint pain (9.3%), hematemesis and malena (8%), diarrhea (5.3%), proptosis (2 cases), dysphagia, mediastinal mass and parotid swelling (1 case each). Uncommon clinical presentations lead to delay in diagnosis in some cases. Awareness of uncommon signs and symptoms of childhood leukemia together with laboratory tests may help in earlier diagnosis and proper management of the patients.

Cutaneous metastasis from follicular variant of papillary thyroid carcinoma: a case diagnosed on cytology.

A 40-year-old woman presented with a scalp swelling. A careful clinical examination revealed a left-sided deep-seated thyroid nodule. Fine needle aspiration from both sites disclosed a microfollicular architectural pattern on Giemsa stain and pale nuclei with nuclear grooves on Papanicolaou stain, indicating the possibility of follicular variant of papillary thyroid carcinoma with metastasis to the scalp. Histologic tissue evaluation confirmed the diagnosis. Thus, a diligent search for nuclear features should be performed to enable a diagnosis of follicular variant of papillary thyroid carcinoma on cytology. This helps in patient management obviating the need for a second surgical intervention.

Cytodiagnosis of filarial infections from an endemic area.

OBJECTIVE: To throw light on cytologic findings as a possible mode of diagnosis of lymphatic filariasis. STUDY DESIGN: Filariasis has worldwide distribution, but lymphatic filariasis predominantly affects tropical and subtropical regions. Demonstration of microfilaremia, the specific test for diagnosis of lymphatic filariasis, often shows false negative results in endemic areas. The present study, done in an endemic area, showed the presence of microfilariae or adult worms of Wuchereria bancrofti in fine needle aspirates collected from amicrofilariaemic cases. In a few cases the discovery was incidental. A total 4,534 cases undergoing cytologic evaluation were carefully screened for the presence of adult worms or larvae, irrespective of clinical diagnosis. Microfilariae were demonstrated in both clinically suspected cases of filariasis and asymptomatic cases. RESULTS: A total of 1 positive cases were found; in 4 cases the clinical diagnosis was lymphatic filariasis, and 7 cases were asymptomatic. All 11 cases were amicrofilariaemic. CONCLUSION: Various sophisticated investigations are used for diagnosis of lymphatic filariasis without microfilaremia. Fine needle aspiration cytology, being a cheap, simple and easy procedure, may have some role in this field, but further detailed studies are needed before any final claim.

Gastro-intestinal stromal tumour--role of CD117 in diagnosis and management.

Gastro-intestinal stromal tumours (GIST) are a biologically distinct heterogenous group of tumours of the gut. They are said to arise from interstitial cells of Cajal in gut wall. The turnour results from mutation of c-kit gene which codes for CD117 containing tyrosine kinase receptor of Cajal cells. Identification of this mutation by immunohistochemistry (IHC) is the key to the diagnosis of these tumours. CD117 negative GISTs develop from gene mutation through alternate pathway (PDGFRA). The accurate diagnosis is important as specific chemotherapeutic agents are now available for their management. We have studied 8 cases of GISTs during last 2 years in our institute. Half of the cases were female, six cases were in the age group between 35 to 50 years, the other two being of 19 and 70 years. On histology, 5 cases were categorized as high grade on the basis of their size and mitotic count. All cases were subjected to IHC. Only 4 cases were CDll7 positive, one case was positive for S100 and one case for SMA. Remaining 2 cases, negative for CD117, S100 and SMA, histologically resembled GISTs. CD117 positive cases are ideal candidates for treatment with molecularly targeted specific chemotherapeutic agents, e.g., imatinib as these tumours are non-responsive to conventional chemotherapy. Histologically diagnosed stromal tumours of the gut should be subjected to immunostain for CD117 so that specific medical management can be provided to prevent recurrence and metastasis as well as pre-operative debulking of the tumour.

Primary non-Hodgkin's lymphoma of breast: a case report.

Primary breast lymphoma is a relatively uncommon neoplasm, majority being of B-cell origin. Mucosa associated lymphoid tissue (MALT) is one of the common types of breast lymphomas. Though cytologic diagnosis of breast lymphoma is an easy procedure and provides guidance for appropriate pre-operative management, it is often impossible to differentiate a low grade lymphoma from reactive proliferation. A similar difficulty was encountered in the present case, a 42 year old female with a breast lump. Fine needle aspiration cytology revealed a mixed lymphoid cell population. Lymphoepithelial lesions were identified histologically, and the majority of the cell population were confirmed as lymphoma cells of B-cell origin on immunohistochemistry. This case highlights the limitations of cytology and the importance of histological examination supported by immunohistochemistry for making a diagnosis of low grade primary breast lymphoma.

Small cell carcinoma of ovary: a rare pathology.

A 15-year-old girl presented with rapidly developing ascites and bilateral tender pelvic masses, diagnosed as small cell carcinoma of the ovary, based on histopathological and immunohistochemical features. The case is being presented because of its rare occurrence.

Recurrent and aggressive chondroblastoma: a case report.

Recurrent chondroblastoma with pulmonary and palatal metastasis is a rare occurrence. We report the cytological and histological findings of such a case in a 33 years old male, where the primary diagnosis of metastatic chondroblastoma was made on FNAC, which was later confirmed on histopathology. The present case highlights that, some chondroblastomas do exist, that are capable of pursuing a malignant course.

Adrenal myelolipoma--report of a case.

Adrenal myelolipoma is a rare, benign, non-secreting tumour composed of adipose and haematopoietic tissue. One such rare case in a 32-year-old female who presented with'pain in right lumbar region is reported here. CT scan revealed a mass in the suparenal region measuring 5.6 x 5 cm. In view of the size and symptomatic nature of the mass, surgical resection was performed. Histological examination revealed the features of myelolipoma. The outcome was favourable without recurrence after a follow-up of one year.

Immature mediastinal teratoma--a rare pathology.

A 9 year old female presented with 8 months history of right sided chest pain and respiratory distress. Chest X-ray revealed a large anterior mediastinal mass. Histopathology of the mass revealed features of an immature teratoma. The case is being presented because of its rare occurrence in the mediastinum.

Thymolipoma--a case report.

A 28 year old male presented with a 8 months history of chest pain, cough and breathlessness. CT scan revealed a large mass in right anterior mediastinum showing fat and soft tissue attenuation. Histopathology of the resected mass revealed a tumour showing extensive areas of mature fat and relatively less interspersed thymic tissue confirming thymolipoma. Because of its rarity, we are presenting this case with a brief review of literature.