Amita Maheshwari

Spectrum of neuroendocrine carcinomas of the uterine cervix, including histopathologic features, terminology, immunohistochemical profile, and clinical outcomes in a series of 50 cases from a single institution in India.

Neuroendocrine carcinomas of the cervix are uncommon, characterized by a histomorphological spectrum and, mostly, an aggressive clinical course. There are only few substantial studies on such cases documented from our country, where cervical cancer is the second most common cancer affecting women. Herein, we present a spectrum of 50 cervical neuroendocrine carcinomas, including histopathologic features, terminology, immunohistochemical (IHC) profile, and clinical outcomes, wherever available. Fifty tumors occurred in women, with their age ranging from 23 to 69 years (mean, 48.6 years; median, 46.5 years). Stagewise, among 25 cases, most cases (6, or 24%) presented with stage IB. Average tumor size was 4.7 cm. On histopathologic review, 26 tumors (52%) were classified as small cell carcinoma (SMCA); 14 (28%), as large cell neuroendocrine carcinomas (LCNECs); 4 (8%), as SMCA+LCNECs; and 6, as mixed carcinomas, including 3 tumors (6%) with SMCA and squamous cell carcinoma (SCC), 2 tumors (4%) with LCNEC and adenocarcinoma, and a single tumor (2%) with LCNEC and squamous cell carcinoma. On IHC performed in 41 tumors (82%), 36 tumors (87.8%) were positive for at least a single neuroendocrine marker, and 22 (53.6%) expressed 2 neuroendocrine markers. Synaptophysin was positive in 22 (59.4%) of 37 tumors; chromogranin, in 27 (72.9%) of 37; CD56, in 8 (100%) of 8; and neuron-specific enolase in 7 (87.5%) of 8 tumors. Treatment wise, among 30 patients (60%), 6 (20%) underwent surgery, including Wertheim hysterectomy (5) and simple hysterectomy (1); 8 (26.6%) underwent surgery with adjuvant treatment, and 10 patients (33.3%) were offered chemotherapy and/or radiotherapy. On follow-up (27 patients, or 54%) over 1 to 144 months, 16 patients (59.2%) were alive with disease over median duration of 9 months, and 7 (25.9%) were free of disease over median duration of 26.5 months. There were 5 recorded deaths. Thirteen tumors (48.1%) metastasized, most commonly to liver. In cases with early stage disease and adjuvant treatment, including radiotherapy, LCNEC histology fared well. This study forms the largest documented series on cervical neuroendocrine carcinomas from our country, testifying the current histopathologic classification system. Although SMCAs can be recognized on morphology, LCNECs need to be correctly identified because these can be misdiagnosed in the absence of neuroendocrine markers. Synaptophysin, chromogranin, and CD56 are optimal IHC markers. Small cell carcinomas, pure or mixed, are relatively more aggressive. All these tumors are best treated with multimodal therapy. Early stage disease treated with radical surgery and adjuvant treatment seems to increase survival. Despite aggressive treatment, prognosis is dismal.

IGF-1R inhibition potentiates cytotoxic effects of chemotherapeutic agents in early stages of chemoresistant ovarian cancer cells

The kinetics and effect of hyper activated IGF-1R signaling is not well investigated during acquirement of platinum and taxol resistance in ovarian cancer cells. Herein we reported an upregulated IGF-1R expression in early stages of cisplatin paclitaxel and cisplatin-taxol resistance. Picropodophyllin, an IGF-1R inhibitor, alone and in combination with cisplatin, paclitaxel or both at lowest possible doses could reverse the resistance at early stages. Upregulated IGF-1R was also found in primary tumors of ovarian cancer patients after three to four cycles of platinum-taxol treatment. These findings indicate that a combination of cytotoxic agents and IGF-1R inhibitor is more effective at early stages of chemoresistant ovarian cancer.

Accuracy of intraoperative frozen section in the diagnosis of ovarian neoplasms: Experience at a tertiary oncology center

BackgroundEpithelial ovarian neoplasms are an important cause of morbidity and mortality in women. The surgical management of ovarian neoplasms depends on their correct categorization as benign, borderline or malignant. This study was undertaken to evaluate the accuracy of intra-operative frozen section in the diagnosis of various categories of ovarian neoplasms.MethodsIntraoperative frozen section diagnosis was retrospectively evaluated in 217 patients with suspected ovarian neoplasms who underwent surgery as primary line of therapy at our institution. This was compared with the final histopathologic diagnosis on paraffin sections.ResultsIn 7 patients (3.2%) no opinion on frozen section was possible. In the remaining 210 patients frozen section report had a sensitivity of 100%, 93.5% and 45.5% for benign, malignant and borderline tumors. The corresponding specificities were 93.2%, 98.3% and 98.5% respectively. The overall accuracy of frozen section diagnosis was 91.2%. The majority of cases of disagreement were in the mucinous and borderline tumors.ConclusionIntraoperative frozen section has high accuracy in the diagnosis of suspected ovarian neoplasms. It is a valuable tool to guide the surgical management of these patients and should be routinely used in all major oncology centers.

Acute non-ST elevation myocardial infarction following paclitaxel administration for ovarian carcinoma: A case report and review of literature

We report a case of an acute non-ST elevation myocardial infarction (AMI) induced by paclitaxel in a patient with ovarian cancer. A 45-year-old premenopausal lady without any co-morbidity was started on the first cycle of neoadjuvant chemotherapy with paclitaxel-based regimen for advanced stage ovarian cancer. The patient developed chest pain 3 h after paclitaxel infusion with characteristic electrocardiographic changes of antero-apical myocardial infarction. The patient recovered on conservative medical management with reversion of electrocardiogram (ECG) changes. Cardiac ischemia and myocardial infarction, possibly due to coronary vasospasm, are rare adverse effects of paclitaxel with reported incidence of 0.26%. We have reported a case of paclitaxel-induced myocardial infarction with reversible cardiac dysfunction. The possibility of myocardial infarction should be considered in patients who develop chest pain or other symptoms after paclitaxel infusion.

In vivo Raman spectroscopy of human uterine cervix: exploring the utility of vagina as an internal control

Abstract. In vivo Raman spectroscopy is being projected as a new, noninvasive method for cervical cancer diagnosis. In most of the reported studies, normal areas in the cancerous cervix were used as control. However, in the Indian subcontinent, the majority of cervical cancers are detected at advanced stages, leaving no normal sites for acquiring control spectra. Moreover, vagina and ectocervix are reported to have similar biochemical composition. Thus, in the present study, we have evaluated the feasibility of classifying normal and cancerous conditions in the Indian population and we have also explored the utility of the vagina as an internal control. A total of 228 normal and 181 tumor in vivo Raman spectra were acquired from 93 subjects under clinical supervision. The spectral features in normal conditions suggest the presence of collagen, while DNA and noncollagenous proteins were abundant in tumors. Principal-component linear discriminant analysis (PC-LDA) yielded 97% classification efficiency between normal and tumor groups. An analysis of a normal cervix and vaginal controls of cancerous and noncancerous subjects suggests similar spectral features between these groups. PC-LDA of tumor, normal cervix, and vaginal controls further support the utility of the vagina as an internal control. Overall, findings of the study corroborate with earlier studies and facilitate objective, noninvasive, and rapid Raman spectroscopic-based screening/diagnosis of cervical cancers.

Primary vaginal Ewing's sarcoma or primitive neuroectodermal tumor in a 17-year-old woman: a case report

IntroductionPrimary Ewings sarcoma or primitive neuroectodermal tumor of the genital tract of women is uncommon. Rarer still is its occurrence in the vagina, with only five cases described so far. Out of these, only one case was confirmed using molecular analysis.Case presentationWe present an extremely rare case of Ewings sarcoma or primitive neuroectodermal tumor in a 17-year-old Indian girl. She presented with a vaginal mass that was initially diagnosed as a malignant round cell tumor. Immunohistochemistry showed diffuse positivity for vimentin, membranous positivity for MIC2, and positivity for BCL2 and FLI-1. On the other hand, she was negative for cytokeratin, epithelial membrane antigen, desmin, Myo D-1, myogenin and smooth muscle actin. A diagnosis of primitive neuroectodermal tumor was thus offered. Furthermore, a molecular analysis of our patient using reverse transcription-polymerase chain reaction technique showed positivity for t(11; 22) (q24; q12) (EWSR1-FLI1), thus confirming the diagnosis of a Ewings sarcoma/primitive neuroectodermal tumor. Our patient was offered chemotherapy on Institutional protocol EFT 2001.ConclusionThis is a rare case of primary vaginal Ewings sarcoma or primitive neuroectodermal tumor, which was confirmed with molecular analysis, in the youngest patient known so far. This study reinforces the value of integrating morphological features with membranous MIC2 positivity, along with application of molecular techniques in objective identification of an Ewings sarcoma or primitive neuroectodermal tumor at uncommon sites.

Uterine smooth muscle tumors of uncertain malignant potential and atypical leiomyoma: A morphological study of these grey zones with clinical correlation

OBJECTIVES To study the histological features in uterine STUMP, and atypical leiomyomas (AL), and to correlate with clinical outcome. MATERIALS AND METHODS From January 2004 to August 2010, a total of 21 cases were retrieved from records, labeled as STUMP(7), AL (5), AL with low risk of recurrence (2), smooth muscle tumor of low malignant potential (STLMP) (2), and symplastic leiomyoma (5). The slides were reviewed for coagulative tumor cell necrosis (CTCN), hyaline necrosis/ infarction type necrosis, presence and degree of cytological atypia, mitotic activity, epithelioid morphology and myxoid features. The other characteristics (such as size, circumscription, individual tumor cell necrosis), were noted, wherever available. RESULTS The mean age was 45 years (median 46; range 24-67 yrs). CTCN was seen in 2 cases on examination of additional material; wherein a revised diagnosis of leiomyosarcoma had been given. Infarction type necrosis and individual cell necrosis was seen in 2 and 3 cases, respectively. Mitoses were less than 5/10 hpf in all the cases. One of the tumours labeled as STUMP also had concurrent endometrial adenocarcinoma. Follow up: Follow-up was available in 11 cases (52.3%). One patient had died. (cause not known). In 10 patients, the follow-up ranged from 4 to 56 months (mean 20.9 months; median 15 months) nine patients were alive and well. One patient (labeled STLMP) had metastatic liver disease 3 yrs after the primary surgery, at the last follow-up. CONCLUSIONS 1) There is an overlap in using the terminologies as STUMP, AL, AL with low risk of recurrence, AL with low malignant potential. A designation of STUMP does convey a category of borderline malignancy to the gynecological surgeons. Most behave in a benign fashion and follow-up without adjuvant therapy is currently recommended. Critical evaluation of coagulative tumor necrosis is essential. Follow-up remains a challenge in our setting.

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.

Neoadjuvant Chemotherapy Followed by Radical Surgery Versus Concomitant Chemotherapy and Radiotherapy in Patients With Stage IB2, IIA, or IIB Squamous Cervical Cancer: A Randomized Controlled Trial

Purpose We compared the efficacy and toxicity of neoadjuvant chemotherapy followed by radical surgery versus standard cisplatin-based chemoradiation in patients with locally advanced squamous cervical cancer. Patients and Methods This was a single-center, phase III, randomized controlled trial ( ClinicalTrials.gov identifier: NCT00193739). Eligible patients were between 18 and 65 years old and had stage IB2, IIA, or IIB squamous cervical cancer. They were randomly assigned, after stratification by stage, to receive either three cycles of neoadjuvant chemotherapy using paclitaxel and carboplatin once every 3 weeks followed by radical hysterectomy or standard radiotherapy with concomitant cisplatin once every week for 5 weeks. Patients in the neoadjuvant group received postoperative adjuvant radiation or concomitant chemotherapy and radiotherapy, if indicated. The primary end point was disease-free survival (DFS), defined as survival without relapse or death related to cancer, and secondary end points included overall survival and toxicity. Results Between September 2003 and February 2015, 635 patients were randomly assigned, of whom 633 (316 patients in the neoadjuvant chemotherapy plus surgery group and 317 patients in the concomitant chemoradiation group) were included in the final analysis, with a median follow-up time of 58.5 months. The 5-year DFS in the neoadjuvant chemotherapy plus surgery group was 69.3% compared with 76.7% in the concomitant chemoradiation group (hazard ratio, 1.38; 95% CI, 1.02 to 1.87; P = .038), whereas the corresponding 5-year OS rates were 75.4% and 74.7%, respectively (hazard ratio, 1.025; 95% CI, 0.752 to 1.398; P = .87). The delayed toxicities at 24 months or later after treatment completion in the neoadjuvant chemotherapy plus surgery group versus the concomitant chemoradiation group were rectal (2.2% v 3.5%, respectively), bladder (1.6% v 3.5%, respectively), and vaginal (12.0% v 25.6%, respectively). Conclusion Cisplatin-based concomitant chemoradiation resulted in superior DFS compared with neoadjuvant chemotherapy followed by radical surgery in locally advanced cervical cancer.

Clinico-pathological spectrum of primary ovarian malignant mixed mullerian tumors (OMMMT) from a tertiary cancer institute: A series of 27 cases

AIMS AND OBJECTIVES To study the clinico-pathological characteristics of primary ovarian malignant mixed mullerian tumor (OMMMT) and assess the prognostic factors associated with treatment outcome and survival. MATERIALS AND METHODS The pathology database was searched for primary ovarian carcinosarcoma diagnosed and/or managed at our institute from period of January 2004 to July 2010. The histological sections were reviewed, with emphasis on type and grade of epithelial and sarcomatous components. The medical records were retrospectively analyzed for clinical details and follow up. RESULTS A total of 27 cases of primary ovarian carcinosarcoma were identified. The median age at diagnosis was 51 years. Fourteen patients had advanced stage (stage III and IV) at presentation. Cytoreductive surgery was done in 18 cases, and 7 had received upfront chemotherapy. Histologically, 10 cases had epithelial predominance (> 50% epithelial component) and 11 had sarcoma predominance. The most frequent epithelial component was endometroid type, and most common sarcoma component was rhabdomyosarcomatous. Hyaline droplets within sarcomatous stroma were seen prominently in 15 cases. Three cases showed germ cell /yolk sac-like areas. Eighteen cases had follow up with a median of 15 months (4-40 months). The recurrence-free survival in advanced stage and sarcoma predominant was 10.5 months in comparison to 13 months in early stage and epithelial predominant OMMMT. CONCLUSION Primary ovarian carcinosarcoma is a rare biphasic malignancy with variable proportions of epithelial and spindle elements. Presence of hyaline droplets within spindle sarcoma in a biopsy from ovarian mass should alert the pathologists regarding MMMT. Advanced stage, suboptimal cytoreduction, and sarcoma predominant tumors are likely to have a worse outcome in ovarian MMMT.