Roshan F. Chinoy

HPV Screening for Cervical Cancer in Rural India

BACKGROUND In October 1999, we began to measure the effect of a single round of screening by testing for human papillomavirus (HPV), cytologic testing, or visual inspection of the cervix with acetic acid (VIA) on the incidence of cervical cancer and the associated rates of death in the Osmanabad district in India. METHODS In this cluster-randomized trial, 52 clusters of villages, with a total of 131,746 healthy women between the ages of 30 and 59 years, were randomly assigned to four groups of 13 clusters each. The groups were randomly assigned to undergo screening by HPV testing (34,126 women), cytologic testing (32,058), or VIA (34,074) or to receive standard care (31,488, control group). Women who had positive results on screening underwent colposcopy and directed biopsies, and those with cervical precancerous lesions or cancer received appropriate treatment. RESULTS In the HPV-testing group, cervical cancer was diagnosed in 127 subjects (of whom 39 had stage II or higher), as compared with 118 subjects (of whom 82 had advanced disease) in the control group (hazard ratio for the detection of advanced cancer in the HPV-testing group, 0.47; 95% confidence interval [CI], 0.32 to 0.69). There were 34 deaths from cancer in the HPV-testing group, as compared with 64 in the control group (hazard ratio, 0.52; 95% CI, 0.33 to 0.83). No significant reductions in the numbers of advanced cancers or deaths were observed in the cytologic-testing group or in the VIA group, as compared with the control group. Mild adverse events were reported in 0.1% of screened women. CONCLUSIONS In a low-resource setting, a single round of HPV testing was associated with a significant reduction in the numbers of advanced cervical cancers and deaths from cervical cancer.

Clinicomorphologic features of a series of 10 cases of malignant triton tumors diagnosed over 10 years at a tertiary cancer hospital in Mumbai, India

A rhabdomyoblastic differentiation in a malignant peripheral nerve sheath tumor is unusual and is termed as a malignant triton tumor. A series of 10 such cases with their clinicomorphological features, diagnosed over a 10-year period, is presented. The average age of occurrence was 30 years, with the maximum number of cases in the second decade and with male outnumbering female patients. More cases were seen in the setting of neurofibromatosis. On histology, 80% of the cases were of high grade. Distinct rhabdomyoblastic cells were identified in the areas of malignant peripheral nerve sheath tumor. Immunohistochemistry confirmed the neurogenic differentiation with varying S-100 expression and the rhabdomyoblastic differentiation with desmin and myoglobin positivity in all cases. Surgery with adequate margins constituted the treatment mainstay with adjuvant chemotherapy and/or radiotherapy in individual cases. On follow-up with 7 cases, 3 showed local recurrences, including one that, in addition to another 2 cases, showed lung metastasis. One patient died of the disease. This case along with another high-grade case displayed a diffuse Ki-67 and p53 positivity. Malignant triton tumor is an uncommon tumor associated with an aggressive behavior. Surgery with clear margins is the treatment mainstay. Adjuvant radiotherapy is effective.

Proteomic profiling of cancer of the gingivo-buccal complex: Identification of new differentially expressed markers

Tobacco‐related oral cancer is the most common cancer among Indian males, gingivo‐buccal complex (GBC) being the most affected subsite due to the habit of chewing tobacco. Proteins from the lysates of microdissected normal and transformed epithelium from clinically well‐characterized tissue samples of the GBC were separated by two‐dimensional gel electrophoresis to identify differentially expressed proteins. Eleven protein spots showed differential expression, which could withstand the stringency of statistical evaluation. The observations were confirmed with additional tissues. Nine of these differentiators were identified by MS as lactate dehydrogenase B, α‐enolase, prohibitin, cathepsin D, apolipoprotein A‐I, tumor protein translationally controlled‐1, an SFN family protein, 14‐3‐3σ and tropomyosin. Cluster analysis indicated that these proteins, as a coexpressed set, could distinguish normal and transformed epithelium. Functionally, these differentiator molecules are relevant to the pathways and processes that have been previously implicated in oral carcinogenesis and could therefore be investigated further as a panel of markers for management of cancer of the GBC.

Epithelioid trophoblastic tumor of uterus presenting as an ovarian mass: a diagnostic and therapeutic dilemma.

Epithelioid trophoblastic tumor (ETT) is a rare gestational trophoblastic tumor and often poses a diagnostic and therapeutic challenge to the involved clinicians. We report a case of epithelioid trophoblastic tumor in a young woman which involved the uterus, parametrium and the right ovary. Misdiagnosis as a choriocarcinoma led to improper treatment and progressive disease. Microscopically it revealed a relatively monotonous population of epithelioid cells arranged in nests with hyaline-like matrix surrounding the tumor cells. Differential diagnosis between placental site trophoblastic tumor and carcinoma was ruled out based on histology and immunohistochemistry. The patient developed lung and brain metastasis after 10 months and is alive with disease 1(1/2) years thereafter and is taking palliative chemotherapy. The patient had beta-HCG level of 85.1 mIU/mL at the time of diagnosis; but just before metastasis, the levels rose. Awareness of the histological features of ETT is essential to avoid misdiagnosis, as it represents a tumor which is primarily treated by surgery rather than with chemotherapy.

Critical Role of Fine Needle Aspiration Cytology and Immunocytochemistry in Preoperative Diagnosis of Pediatric Renal Tumors

OBJECTIVE To evaluate accuracy and role of immunocytochemistry (ICC) in cytologic diagnosis of pediatric renal tumors. STUDY DESIGN Fine needle aspirates from 75 cases of pediatric renal tumors were studied. Radiologic-guided aspirations were performed, with 6-7 smears stained with Papanicolaou and Giemsa stains. Smears were screened without the knowledge of final histologic diagnosis. Subsequently, clinical details, final histology and diagnosis rendered by the original cytologist were noted to judge accuracy of diagnosis by a sensitized cytologist. Five neuroblastomas that entered close differentials for Wilms tumor were also evaluated. ICC studies were also performed after staining. RESULTS Of 58 Wilms tumors, 5 were misdiagnosed; 3 renal rhabdoid tumors and 1 clear cell sarcoma were missed on cytology. Non-Hodgkins lymphomas presenting as renal masses were accurately diagnosed on cytology, but primitive neuroectodermal tumors (n = 3) and renal cell carcinomas (n = 2) were not accurately diagnosed. Accuracy rate improved from 65% to 92% on review by a cytologist aware of cytologic features of pediatric renal tumors. CONCLUSION A good accuracy rate of diagnosis of pediatric renal tumors can be achieved by priming pathologists to typical features of tumors. Immunocytochemistry plays a supportive role in cases with atypical morphology or unusual presentations.

Immunocytochemistry on Scrape Cytology in Breast Cancer

Objective To standardize the technique of immunocytochemical (ICC) assessment of estrogen (ER) and progesterone receptor (PR) status in breast cancer by scrape cytology and to compare the results with immunohistochemistry on paraffin blocks. Study Design ICC assessment for ER and PR was done on scrape smears from tissue samples in 200 cases of primary breast cancer. The results were compared to those obtained from immunohistochemical (IHC) evaluation of formalin-fixed paraffin sections obtained from the same tissue samples. Results ER/PR positivity rates as well as staining scores were compared between the scrape smears and tissue sections. The concordance between cytology and histology was 84% for ER and 90% for PR. Both the positivity rates and the staining intensity scores were higher for cytochemistry than for histochemistry. Conclusion The ICC method on scrape smears is a simple test with rapid turnaround time. The sample required is sm,all, and antigen loss due to fixation and processing is minimal. This new method gives a higher yield of hormone receptor positivity and, when used in conjunction with the IHC method, may improve the pickup rate of ER-positive cases, thereby playing an important role in risk stratification and therapeutic decision making in patients with breast cancer.