Deepti Joshi

Are viruses associated with human breast cancer? Scrutinizing the molecular evidence

The three viruses most studied as possible causes of human breast cancer are mouse mammary tumor virus-like sequences (MMTV-LS), Epstein-Barr virus (EBV), and oncogenic (high risk) types of human papilloma virus (HPV). The first step in fulfilling traditional criteria for inferring that a cancer is caused by a virus is to demonstrate the virus in the affected tissue. Molecular techniques, compared to host antibody assessment and immunohistochemistry, are the most definitive in establishing viral presence. Results of 85 original molecular research investigations to detect one or more of the three viruses have been extremely divergent with no consensus reached. We evaluated the methodology of these studies for the following: type of molecular assay, DNA/RNA quality control, positive and negative assay controls, type of fixation, genome targets, methods for preventing and detecting molecular contamination, pathology of specimens processed, sample size, and proportion of specimens positive for the viral genome region targeted. Only seven of the studies convincingly demonstrated the presence of an oncogenic virus biomarker (EBV: 4/30 studies (13%); HPV 3/29 studies (10%), whereas 25 convincingly demonstrated absence of the virus studied (MMTV-LS: 4/25 (16%); EBV: 15/30 (50%); 6/29 (21%). The remainder of the studies suffered shortcomings, which, in our opinion, prevented a definitive conclusion. Only one of the studies compared frequency of the virus in breast tissue of breast cancer patients versus appropriate normal control subjects with no history of breast cancer. None of the studies were designed as epidemiologic studies to determine if the presence of the virus was significantly associated with breast cancer. Based on our evaluation, the data in the publications reviewed here remain preliminary, and do not justify a conclusion that MMTV-LS, HPV, or EBV are causally associated with breast cancer. However, they form a valuable basis for redirecting future studies.

Association of Epstein Barr Virus Infection (EBV) with Breast Cancer in Rural Indian Women

Introduction Breast cancer is the most common malignancy affecting females worldwide but conventional risk factors are able to explain only a small proportion of these cases. A possible viral etiology for breast cancer has been proposed and Epstein-Barr Virus (EBV) is a widely researched candidate virus. The aim of the present study, first one of its kind from India, was to determine if there is a greater association of EBV infection with breast cancer patients as compared to patients with benign breast diseases. Methods We looked for expression of Epstein-Barr Virus Nuclear Antigen-1 (EBNA-1) in breast cancer tissue specimens by employing immunohistochemistry (IHC). We also measured levels of anti-EBNA-1 Immunoglobulin (IgG) antibodies in stored sera of these patients using commercial Enzyme linked Immunosorbent Assay (ELISA) kit. Patients with benign breast diseases were used as a comparison group for both immunohistochemical and serological analysis. Results 58 cases of malignant breast disease and 63 of benign breast disease (controls) were included in the study. Using manufacturer determined cut-off of 3 IU/ml, 50/55 tested (90.9%) cases and 27/33 tested (81.8%) controls were seropositive for anti-EBNA-1 IgG. Mean antibody levels were significantly higher for cases (54.22 IU/ml) as compared to controls (18.68 IU/ml). IHC for EBNA-1 was positive in 28/51 cases (54.9%). No IHC positivity was noted in the tested 30 controls. Our results show that EBNA-1 expression is seen in a significant proportion of breast cancer tissue specimens from rural India and as compared to patients with benign breast diseases these patients also have a higher immunological response against EBNA-1.

Metaplastic Carcinoma of the Breast: Cytological Diagnosis and Diagnostic Pitfalls

Objective: Metaplastic carcinoma of the breast is a rare malignant neoplasm comprised of ductal, squamous and/or mesenchymal elements in various proportions. Fine needle aspiration diagnosis of this entity is problematic because of its pathological heterogeneity. In this study, we have described the cytomorphological features of histologically confirmed metaplastic carcinomas and also discussed the diagnostic limitations along with a brief review of the literature. Study Design: In this observational study, the histology and cytology files of all cases identified as metaplastic carcinomas during the study period (2004–2009) were retrieved. The slides were reviewed for the presence of various elements. Results: Ten cases were identified as metaplastic carcinomas during the study period. All cases were diagnosed as malignant on cytology. Three cases showed presence of squamous carcinoma cells, 4 showed presence of atypical spindle cells, 2 showed presence of mesenchymal fragments and 1 showed presence of osteoclastic giant cells. Conclusion: The presence of biphasic tumor cells, atypical spindle cells admixed with poorly differentiated carcinoma cells, squamous carcinoma cells, osteoclastic giant cells and matrix may provide clues for the fine needle aspiration diagnosis of metaplastic carcinomas. However, cytological diagnosis may not be possible in all the cases because of selective sampling of various pathological elements.

Cytomorphologic diagnosis of basaloid squamous cell carcinoma: a case report.

BACKGROUND Basaloid squamous cell carcinoma is a high-grade variant of squamous cell carcinoma that most commonly occurs in the upper aerodigestive tract. There are limited case reports of this entity in the cytology literature. The authors describe the cytologic features of a histologically confirmed case of basaloid squamous cell carcinoma arising in the floor of the mouth. CASE A 51-year-old woman presented with a swelling in the floor of the mouth. Fine needle aspiration was performed; the aspirate comprised groups, sheets and a dispersed population of small to medium-sized cells with hyperchromatic nuclei and scant cytoplasm. Extracellular basement membrane-like material was also noted, which led to the erroneous diagnosis of adenoid cystic carcinoma. Histopathology characteristically revealed the presence of squamoid nests between malignant basaloid cells, and the tumor was finally diagnosed as basaloid squamous cell carcinoma. Occasional groups of squamoid cells were observed in the aspirate on retrospective evaluation. CONCLUSION Basaloid squamous cell carcinoma should be considered in the differential diagnosis of tumors arising in oral cavity. Cytologic diagnosis may be difficult, but careful search for a second cell population of squamoid cells in addition to small basaloid cells may aid in rendering the correct diagnosis.

Xanthogranulomatous salpingitis with enterobial appendicitis

The differential diagnosis of pelvic and lower abdominal pain associated with adnexal masses in a female patient includes pelvic inflammatory disease, endometriosis and gynaecological malignancy (Schnell et al. 1992). Although Enterobius vermicularis infestation is generally asymptomatic, there are reports indicating that Enterobius infestation may cause granulomatous salpingitis (Shroff et al. 2008; Vinuela et al. 1979). We report a case of xanthogranulomatous salpingitis in a 37-year-old woman presenting with acute abdomen and right-sided adnexal mass. Histopathological examination of the appendix showed the presence of adult E. vermicularis in the lumen of the appendix. We propose that the xanthogranulomatous salpingitis and oophoritis in this case may result from E. vermicularis infection.

Cytodiagnosis of granulocytic sarcoma of liver arising in a milieu of myeloid metaplasia: a case report.

BACKGROUND Granulocytic sarcoma is an extramedullary tumor that is composed of granulocytic precursor cells. We report an unusual case of granulocytic sarcoma of the liver that arose in the background of myeloid metaplasia. Fine needle aspiration cytology (FNAC) was instrumental in making the diagnosis in absence of previously known Hematlogic abnormality. CASE A 65-year-old woman presented with multiple nodules in the liver. USG-guided FNAC was performed on them. The aspirates showed many myeloid blasts, myelocytes, metamyelocytes, erytbroid precursors and lympboglandular bodies. We considered a differential diagnosis of granulocytic sarcoma and myeloid metaplasia. The presence of erytbroid precursors prompted us to consider myeloid metaplasia as a differential diagnorsis of granulocytic sarcoma. Peripberal smear showed a leukoerytbroblastic reaction. The patient died, and necropsy from the liver revealed extensive infiltration by undfferentiated blast cells with areas of myeloid metaplasia showing maturing erytbroid, myeloid and megakaryocytic elements. CONCLUSION When a dual population of predominant myeloid blasts and normoblarts is encountered, a suspicion of granulocytic sarcoma arising in a background of myeloid metaplasia must be kept. Cells of all 3 lineages may not be always seen in myeloid metaplasia, and 1 cell line may predominate, causing a diagnostic dilemma.

Giant cell tumor of the temporal bone—An unusual presentation

Department of Otorhinolaryngology and Head and Neck Surgery, Jawahar Lal Nehru Medical College, DMIMS(DU), Sawangi, Wardha 442005, Maharashtra, India Department of Radiology, Jawahar Lal Nehru Medical College, DMIMS(DU), Sawangi, Wardha, Maharashtra, India Department of Medicine, Jawahar Lal Nehru Medical College, DMIMS(DU), Sawangi, Wardha, Maharashtra, India Department of Pathology, MGIMS, Sewagram, Wardha, Maharashtra, India Department of Neurosurgery, MGIMS, Sewagram, Wardha, Maharashtra, India

Racemose cysticercosis presenting as cystic neck swelling

Cysticercosis is a parasitic infection caused by the larvae of the tapeworm Taenia solium which occurs in neural and extraneural forms. Latter commonly involves subcutaneous tissue, skeletal muscles, and eyes. Head and neck sites commonly involved are buccal mucosa, tongue, and lips. It presents as single or multiple submucosal/cutaneous firm nodules. We report a case of cysticercosis of the supraclavicular region of the neck where it presented as a large soft cystic swelling. The diagnosis was made by sonography and confirmed by gross and microscopic examination to be racemose cysticercosis. This is a very rare cause of a neck swelling not reported previously in the literature.

Large pulmonary cryptococcoma and cryptococcal meningitis in an immunocompetent patient: a case report.

Pulmonary cryptococcoma is a life threatening mycosis and is an unusual disease for immunocompetent individuals. Herein we report a case of large pulmonary cryptococcoma associated with cryptococcal meningitis, presenting radiologically as a lung mass in right upper lobe, in a previously healthy, HIV negative, immunocompetent young individual. Since cryptococcosis continues to be an important infection in HIV negative patients and is associated with substantial overall and cause‐specific mortality, the need for consideration of this entity in the differential diagnosis of a lung mass is emphasized. Diagn. Cytopathol. 2010;38:929–931.

Unusual histological presentation in neurofibromas: Two case reports

Various histological variants of neurofibroma have been described. The objective of this paper is to discuss the unusual histological findings seen in two cases of neurofibromas associated with neurofibromatosis type 1 Both cases presented with multiple subcutaneous nodules. Surgical excision of the largest nodule was done in both the cases. Histological examination of case no.1 revealed a benign tumor of the peripheral nerve sheath, of neurofibroma type with presence of mucus producing glands. The epithelial component was benign in this case. The second case showed presence of rosettes in between areas of typical neurofibroma.