Sonal Amit

Molecular profiling of ETS and non-ETS aberrations in prostate cancer patients from northern India

Molecular stratification of prostate cancer (PCa) based on genetic aberrations including ETS or RAF gene‐rearrangements, PTEN deletion, and SPINK1 over‐expression show clear prognostic and diagnostic utility. Gene rearrangements involving ETS transcription factors are frequent pathogenetic somatic events observed in PCa. Incidence of ETS rearrangements in Caucasian PCa patients has been reported, however, occurrence in Indian population is largely unknown. The aim of this study was to determine the prevalence of the ETS and RAF kinase gene rearrangements, SPINK1 over‐expression, and PTEN deletion in this cohort.

Primary orbital non-Hodgkin's lymphoma

Non-Hodgkins lymphoma (NHL) can have extra-nodal presentation in approximately 25% of cases unlike Hodgkins lymphoma which rarely involves extra-nodal sites. Extra-nodal lymphoma in the head and neck region is extremely rare. We report a case of 6-year-old girl who presented with medial canthus mass with proptosis, lagophthalmos and no significant loss of vision. CT findings showed an extra-conal homogenous mass lesion in the left orbit along superior and medial orbital wall with extensive destruction of surrounding tissue. Histological sections showed polymorphous population of atypical lymphoid cells accompanied by plasma cells, eosinophils and proliferation of small blood vessels with plump endothelial cells. A diagnosis of NHL was rendered. Further, immunohistochemistry confirmed the lesion as peripheral T-cell lymphoma. The lesion was aggressive in course and the patient succumbed within one-and-half  months of diagnosis.

Cytomorphological features of lymphoepithelial carcinoma of submandibular gland in an adolescent male

A case of lymphoepithelial carcinoma (LEC) occurring in right submandibular gland of a 13-year-old Indian male is presented, wherein the lesion unveiled itself only after multiple fine needle aspiration (FNA) procedures. This unusual neoplasm has high frequency of occurrence in Eskimos and a predilection for the parotid gland. The aspirates obtained were highly cellular comprising tight clusters of atypical epithelial cells with admixture of lymphocytes. Histopathological examination of the resected submandibular gland and lymph node chain was consistent with the diagnosis of LEC. Immunohistochemistry (IHC) revealed cytokeratin (CK)-positive and S-100-negative tumor cells lying admixed with CD45-positive lymphoid cells. A detailed otorhinolaryngological examination with inclusion of multiple biopsies was found negative for any primary tumor. Although histopathological features of this entity are well established, only a handful of case reports describing cytological features of this entity are present in medical literature. We conclude that the cytomorphological features of LEC are sufficiently distinctive to at least, suggest a possibility of this lesion.

Determination of p16 overexpression as an indicator of human papillomavirus infection in oral dysplasia and carcinoma

Context: Oral and pharyngeal cancer, grouped together, is the sixth most common cancer in the world. In the past few years, human papillomavirus (HPV) infection has been suggested as a risk factor for oral cancer apart from traditional risk factors such as smoking, tobacco, and alcohol consumption. Aims: The aim of this study was to determine HPV status of the tumors using polymerase chain reaction (HPV-DNA PCR) and p16 immunostaining and to correlate p16 overexpression as an indicator of HPV-associated oral dysplasia and carcinoma. Settings and Design: A prospective study was conducted in fifty cases of suspected oral cancer. Materials and Methods: PCR Amplification of extracted HPV-DNA was done for HPV-DNA status in fresh tissue of suspected oral cancer cases. Histomorphological features of the cases were analyzed, and p16 immunohistochemistry was performed on the same specimen after making paraffin blocks to study p16 overexpression. Statistical Analysis Used: Chi-square test was used to analyze the differences between discrete variables. Results: 5/6 (83.3%) HPV-DNA-positive cases were positive for p16 expression, whereas 26/44 (59.09%) p16-positive cases which were negative for HPV-DNA. Sensitivity and specificity of p16 as a surrogate marker for HPV-DNA were found to be 83.3% and 40%, respectively. Conclusions: p16 immunostaining is a good first-line assay for eliminating HPV-negative cases from additional analysis, but other causes of p16 overexpression in oral tumorigenesis related to tobacco consumption in keratinizing squamous cell carcinoma needs to be explored further.

Errors, limitations, and pitfalls in the diagnosis of central and peripheral nervous system lesions in intraoperative cytology and frozen sections.

Context: Intraoperative cytology and frozen section play an important role in the diagnosis of neurosurgical specimens. There are limitations in both these procedures but understanding the errors and pitfalls may help in increasing the diagnostic yield. Aims: To find the diagnostic accuracy of intraoperative cytology and frozen section for central and peripheral nervous system (PNS) lesions and analyze the errors, pitfalls, and limitations in these procedures. Settings and Design: Eighty cases were included in this prospective study in a span of 1.5 years. Materials and Methods: The crush preparations and the frozen sections were stained with hematoxylin and eosin method. The diagnosis of crush smears and the frozen sections were compared with the diagnosis in the paraffin section, which was considered as the gold standard. Statistical Analyses Used: Diagnostic accuracy, sensitivity, and specificity. Results: The diagnostic accuracy of crush smears was 91.25% with a sensitivity of 95.5% and specificity of 100%. In the frozen sections, the overall diagnostic accuracy was 95%, sensitivity was 96.8%, and specificity was 100%. The categories of pitfalls noted in this study were categorization of spindle cell lesions, differentiation of oligodendroglioma from astrocytoma in frozen sections, differentiation of coagulative tumor necrosis of glioblastoma multiforme (GBM) from the caseous necrosis of tuberculosis, grading of gliomas in frozen section, and differentiation of the normal granular cells of the cerebellum from the lymphocytes in cytological smears. Conclusions: Crush smear and frozen section are complimentary procedures. When both are used together, the diagnostic yield is substantially increased.

Tonsillar follicular lymphoma in a child

Follicular lymphomas (FL) are among the most common non-Hodgkins lymphoma (NHL) in adults. However, they are rare in children making up less than 3% of paediatric NHL cases. They occur most commonly in the head and neck region, lymph nodes or tonsils, with occasional extra-nodal occurrences. Distinction of FL from potentially clonal but, reactive follicular hyperplasia is important. We report a case of a 6-year-old male child presenting with night stridor since 6 months. Clinical examination revealed asymmetrical enlargement of the left tonsil. Routine left tonsillectomy was performed and the specimen was sent for histopathological examination. Diagnosis of follicular lymphoma was made on histopathological examination and further confirmed by immunohistochemistry.

Association of AGTR1 (A1166C) and ACE (I/D) Polymorphisms with Breast Cancer Risk in North Indian Population

Renin angiotensin system (RAS) comprising Angiotensin converting enzyme (ACE), Angiotensin II (Ang II) and its receptor Angiotensin II receptor type I (AGTR1), plays a critical role in several diseases including cancer. A single nucleotide polymorphism (SNP) A1166C located in 3′ untranslated region (UTR) of AGTR1 and an insertion/deletion (I/D) polymorphism present in intron 16 of ACE gene have been associated with many diseases, but their association with Breast cancer (BCa) is still debatable. Here, we for the first time investigated the association of these polymorphisms in a North Indian BCa cohort including 161 patients and 152 healthy women. The polymorphisms were evaluated by polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) respectively. The association between these polymorphisms and BCa risk was estimated by calculating Odds Ratio (OR) and chi-square (χ2) test. The DD genotype/D allele of ACE (I/D) polymorphism and “AC and CC” genotype/C allele of AGTR1 (A1166C) polymorphism were associated with higher risk of BCa when evaluated independently. Furthermore, interaction analysis of “AC and CC” and DD genotype and combination of “C and D” alleles of both polymorphisms revealed significantly greater BCa risk than that observed independently. Conclusively, women harboring “AC or CC” genotype/C allele for AGTR1 (A1166C) polymorphism and DD genotype/D allele for ACE (I/D) polymorphisms have a predisposition to develop more aggressive disease with advanced staging and larger tumor size. Our study indicates importance of genetic screening based on these polymorphisms for women, who may have higher risk of BCa.

A Correlative Study Between Transrectal Fnac And Histology Of The Prostate For The Detection Of Prostate Carcinoma.

Aim: To assess the utility of FNAC in diagnosing the prostatic carcinoma .Material and methods: The study of 121 cases was conducted from year 2006 to 2008. The data was analyzed to assess the utility of FNAC for the diagnosis of carcinoma prostate. Results: During the study overall sensitivity and specificity of FNAC were 95.23% and 98.73% respectively and positive predictive value and negative predictive value were 97.56% and 97.50% respectively. The percentage of false positive and false negative cases was 1.26% and 4.76% respectively. Conclusion: The conclusion drawn was that FNAC by trans-rectal route is easiest, accurate, quick method, with minimal discomfort to the patient and outdoor diagnostic procedure for diagnosis of prostatic carcinoma and the result are comparable to that of histopathology.

Recurrent hyperphosphatemic tumoural calcinosis.

Tumoural calcinosis (TC) is a benign gradually developing disorder that can occur in a variety of clinical settings, characterised by subcutaneous deposition of calcium phosphate with or without giant cell reaction. We describe a case of 11-year-old girl presenting with recurrent hard swellings in the vicinity of shoulder and hip joints associated with elevated serum phosphate and normal serum calcium levels. TC has been mainly reported from Africa, with very few cases reported from India. After the diagnosis of hyperphosphatemic TC was established, the patient was treated with oral sevelamer and is under constant follow-up to detect recurrence, if any. The present case highlights the fact that although an uncommon lesion, TC must be considered in the differential diagnosis of subcutaneous hard lump in the vicinity of a joint.

Ependymoblastoma in an adult: a diagnostic challenge on cytology

Ependymoblastoma is a rare, highly malignant brain tumour considered by most to be a subtype of primitive neuroectodermal tumour manifesting in young children. The authors present an unusual case of ependymoblastoma occurring in an 18-year-old female, one of the oldest patients reported with this tumour. The crush smears were highly cellular comprising singly scattered small, round immature cells with fine granular chromatin. The paraffin sections showed a tumour composed of uniform, small-sized, primitive cells forming well defined multi-layered rosettes with prominent mitoses. The tumour cells exhibited diffuse Vimentin and focal glial fibrillary acidic protein reactivity. A few cells showed S-100 reactivity. The patient underwent radiotherapy following complete tumour debulking but, succumbed to the disease within 2 months of diagnosis.