Endometrial serous carcinoma: A retrospective review of histological features & their clinicopathological association with disease-free survival & overall survival

Background & objectives: Endometrial serous carcinoma (ESC) is a high-grade epithelial neoplasm with increased risk for metastasis and recurrence. This study was aimed to assess various histomorphological features of ESC and their clinicopathological association with disease-free survival (DFS) and overall survival (OS). Methods: A total of 205 slides (belonging to 120 patients) diagnosed as ESC from January 2009 to December 2015 were reviewed. Receiver operating characteristics (ROC) curves were established for the diagnostic performance of depth of invasion (DOI), tumour-free distance (TFD) to serosa and percentage myometrial invasion (MI%). OS and DFS were generated by Kaplan-Meier curves and prognostic significance by Cox regression analysis. Results: The mean age at diagnosis was 61.8 yr and the mean tumour size was 4.01 cm. Majority of the females were multiparous (84%; n=94) and postmenopausal (89.2%; n=107). On histopathology, <50 per cent of MI was identified in 37 of the 104 (35%), while 62/104 (59.61%) patients had ?50 per cent MI. Seven (6.7%) patients had full-thickness invasion with serosal involvement, while five (4.8%) patients had no microscopic MI (minimal uterine serous carcinoma). Information about MI was not available in 16 patients. TFD ?7.0 mm, DOI ?6.0 mm and MI% ?40 were significant variables in univariate analyses for OS; however, on multivariate analysis; none of these turned out to be an independent predictor in terms of OS. For DFS, DOI (?6.0 mm) and MI% (?40%) showed a significant association, in univariate as well as multivariate analysis; however, TFD (?7.0 mm) did not show any significant association with DFS. Follow up data were available in 111 of the 120 (92.5%) patients with a five-year OS and DFS of 22.2 and 17.2 per cent, respectively. Interpretation & conclusions: Conventionally calculated DOI (less than or more than half thickness) did not show significance in the present study. Thus, calculating the actual myometrial DOI, MI% and TFD to serosa have the potential for contributing meaningfully to prognostication of ESC

Assessing the histopathology reports of colorectal carcinoma surgery: An audit of three years with emphasis on lymph node yield

Background: A comprehensive histopathology report of colorectal carcinoma surgery is important in cancer staging and planning adjuvant treatment. Our aim was to review histopathology reports of operated specimens of colorectal carcinoma in our institution between 2013 and 2015 to assess different histological parameters, including lymph node yield, and to evaluate compliance to minimum data sets. Methods: After approval by the institutional review board (IRB), we analyzed 1230 histopathology reports of colorectal carcinoma between 2013 and 2015. Various gross and microscopic findings (along with age, sex) were noted, for example, specimen type, tumor site, resection margins including circumferential resection margin (CRM), lymphovascular invasion, perineural invasion, pTNM stage, lymph node yield, etc. Results: Out of 1230 patients, 826 (67.15%) were men and 404 (32.85%) were women. The overall mean age was 52 (range: 18 - 90) years. There were 787 surgeries for rectal cancers. All reports commented on the type of specimen, tumor size (mean = 4.38 cm), proximal, and distal margins. Lymphovascular invasion (LVI) and the pT stage were mentioned in 98.06% and 99.84%, respectively. The overall mean lymph node yield was 18.38 (median = 15, range = 0-130 lymph nodes). A statistically significant difference in lymph node yield was detected between rectal and colonic cancer patients (14.79 and 27.26); post neoadjuvant therapy (NACT) cases, and NACT naive cases (13.51 and 25.11); and high tumor stage and low tumor stage disease (20.60 and 15.22). Not commenting on extramural vascular emboli, tumor budding, and CRM in non-rectal cancer cases were the lacunae. Conclusion: Our compliance with minimal data sets is satisfactory. The overall mean lymph node yield was 18.38 (median = 15). Extramural vascular emboli, tumor budding need to be captured.

Factors influencing women to participate in cervical cancer screening by providing menstrual pads: A population?based study from rural areas of Maharashtra State, India

Background: India accounts for a quarter of the world cervical cancer burden. Cervical cancer is highly preventable. However, low level of participating women in screening is one of the major issues. The aim of this work was to study the factors that influence women to participate in cervical cancer screening by providing menstrual pads for human papillomavirus (HPV) testing. Methods: Menstrual clothes were collected from two different populations from the rural areas of Maharashtra state for HPV testing to screen for cervical cancer. For this study, out of 945 participated women, 557 (58.9%) provided their menstrual pads. Multivariate logistic regression was applied to calculate the odds ratio (OR) and 95% confidence interval (95% CI). Results: The probability of providing the menstrual pads was high among the women who were highly educated compared to those with less education (OR: 1.4; 95% CI: 1.0–1.9), having mobile phone facilities as compared to those with no mobile phones (OR: 1.4; 95% CI: 1.0–2.0), who were using new cloths as menstrual pads compared to those who did not use the same (OR: 8.5; 95% CI: 5.0–14.3), who did not have tobacco habit as compared to those who had tobacco habit (OR: 1.4; 95% CI: 1.1–1.9) and in the village where health worker was stationed as compared to the village where health worker was not stationed (OR: 1.8; 95% CI: 1.4–2.5). Conclusion: Factors including health worker availability, using mobile phones for communication and high education level facilitate women’s participation. To improve the participation, there is need to apply special strategies for older age group, less educated women and women having tobacco habit.

Utility of YWHAE fluorescent in-situ hybridisation in mesenchymal tumors of uterus- An initial experience from tertiary oncology centre in India

Background: Endometrial stromal sarcoma (ESS) is a common uterine mesenchymal malignancy. According to World Health Organisation (WHO) 2014 classification, ESSs are further subdivided into low-grade ESS (LGESS) and high-grade ESS (HGESS). HGESS is defined by the presence of YWHAE gene rearrangement and has a poorer prognosis compared to LGESS. METHODS: Twenty-four cases comprising of 16 endometrial stromal sarcoma and 8 lesions mimicking ESS were retrieved from the archives of the Department of Pathology and subjected to fluorescent in situ hybridization (FISH) analysis for YWHAE gene rearrangement. Immunohistochemistry for CD10, ER, PR, Cyclin D1, SMA, H-Caldesmon, Desmin, Ki-67, and Pan Cytokeratin was performed. RESULTS: Two cases with histological features similar to HGESS were positive for YWHAE gene rearrangement while 1 was indeterminate. No cases of LGESS and histological mimics of ESS were positive for this rearrangement. CONCLUSIONS: HGESSs are defined by the presence of YWHAE rearrangement. These tumors present at higher stage and have poorer prognosis. They may not respond to hormonal therapy and may be treated with chemotherapy. Cyclin D1 though not specific remains a sensitive tool to triage endometrial stromal sarcomas for this FISH study.

A well-differentiated neuroendocrine tumor (Grade I) arising in a tailgut cyst

Tailgut cysts are rare congenital lesions presenting as retrorectal space masses. They can occur in all age groups. Patients often present with ill-defined nonspecific symptoms and the diagnosis if often delayed. Malignancy arising in a tailgut cyst is an even rarer and unique occurrence. A precise diagnosis can be made only after complete excision and histopathological examination of the retrorectal space mass. We describe here a case of a 63-year-old male presenting with chronic constipation, who was diagnosed with a well-differentiated neuroendocrine tumor (Grade I) arising in a tailgut cyst after surgical excision.

Prevalence and nonsexual transmission of human papilloma virus (HPV) in the adolescence girls from rural area of Maharashtra state, India

OBJECTIVE: To find out the prevalence of human papilloma virus (HPV) in adolescent girls and to access the nonsexual transmission of HPV from their mother by using the same old cloth used by their mother. METHOD: Menstrual pads were collected from the women of age group years to find out the presence of HPV and whether it can be used as a cervical cancer screening tool. The results of the said study have been published in the European Journal of Cancer Prevention. During this study, menstrual pads of the daughters of participating women were collected to see the nonsexual transmission of HPV. After conducting the health education and obtaining the informed consent, we interviewed 57 mothers (age group 30–50, married, sexually active) and daughters [age group 12–18, unmarried (not exposed to sex)] from the rural area of Pune district of Maharashtra state, India. The menstrual pads were collected and transported to Mumbai for polymerase chain reaction (PCR) testing. HPV testing was carried out by PCR. RESULTS: Out of 57, 28 (49%) daughters and 23 (40.4%) mothers provided menstrual pad. Out of 23 mothers, one was HPV positive [4.3%: 95% confidence interval (CI) 0.2–23.0] and out of 28 girls, 3 (10.7%: 95% CI 2.0–33.0) were HPV positive. The daughter, whose mother was HPV positive, had negative result for HPV. CONCLUSION: The HPV prevalence in adolescence girls was 10.7%. There may be other nonsexual medium that might have caused HPV in adolescence girls, which needs further research.

Outcomes of advanced epithelial ovarian cancer treated with neoadjuvant chemotherapy

Background: Ovarian cancer is the fourth most common cancer in Indian women. Majority of these are epithelial ovarian cancers (EOCs), most of which present in advanced stage. Women with poor performance status and/or those unlikely to achieve optimal debulking at upfront surgery, benefit from neoadjuvant chemotherapy (NACT) followed by interval cytoreduction, with lesser surgical morbidity and equal survival rates as compared to primary cytoreduction. Methodology: This was a retrospective analysis of patients with advanced ovarian cancer, treated with NACT followed by interval debulking surgery at Tata Memorial Hospital from January 2014 to December 2014. Results: Epithelial cancers constituted 84.4% (n = 406) of all cases of ovarian malignancies. Of these, overwhelming majority (84.3%, n = 342) were in the advanced stage. Sixty percent of all EOC patients received NACT. The mean baseline serum CA-125 level in women treated with NACT was 4294.7 U/ml (range, 11–151,200 U/ml). The median number of NACT cycles (paclitaxel + carboplatin) was 3. Optimal cytoreduction was achieved in 81.5% cases. The rates of Grade 3 or 4 intraoperative and postoperative complications were 4% each. The median postoperative stay was 5 days and the median time between surgery and adjuvant chemotherapy was 20 days. The median progression-free survival (PFS) was 15.15 months (95% confidence interval [CI]: 12.95–17.34), and the median overall survival (OS) was 34.73 months. Multivariate analysis revealed that optimal cytoreduction (hazard ratio [HR] = 2.04 [95% CI: 1.15–3.62]; P = 0.015) and number of NACT cycles (3 vs. >3; HR = 1.51 [95% CI: 1.06–2.16]; P = 0.022) were significantly associated with PFS, and optimal cytoreduction (HR = 3.21 [95% CI: 1.53–6.73]; P = 0.002) and ECOG status (0–1 vs. ≥2; HR = 2.64 [95% CI: 1.25–5.55]; P = 0.011) with OS. Conclusions: High rates of optimal cytoreduction were achieved at interval cytoreductive surgery after NACT, with acceptable surgical morbidity, early start of adjuvant chemotherapy, and survival outcomes comparable to international standards.

Locally advanced cervical cancer: A study of 5-year outcomes

Background: Cervical cancer is the second most common cancer among Indian women. This present retrospective study was conducted to report patient outcomes with locally advanced cervical cancer treated in the year 2010. Materials and Methods: Case records of cervical cancer patients registered from January 1, 2010, to December 31, 2010 were retrieved. A total of 1200 patients were registered, of which 583 received either definitive or adjuvant radiotherapy (RT). Of these, 345 patients who received complete treatment at our hospital were included for outcome analysis. Descriptive statistics were used to summarize patient- and treatment-related variables, and Kaplan–Meier analysis was performed for survival analysis. Results: The median age was 56 years (range: 33–90). Squamous carcinoma was the most common histology (91.4%) and the majority were FIGO Stage III (45.4%). Median follow-up of the cohort was 44 months (1–85 months). The 5-year disease-free survival (DFS) across stages was 50%. Most important predictor of DFS was FIGO staging (Stage II vs. Stage III: 62% vs. 45%) and use of concurrent chemoradiotherapy (CTRT) l (RT vs. CTRT: 32% vs. 57%, respectively). Patients aged >70 years had a significantly poor DFS at 5 years; however, did not have any effect on survival. Grade 3 or more late toxicity was seen in only 5% of the patients. Conclusion: Five-year DFS of 62% and 45% of Stage II and III patients treated under routine care represents comparable stage-matched results to the rest of the world, respectively.

Pulmonary hemangioendothelioma with osteoclast‑like giant cells: A rare observation.

Pulmonary epithelioid hemangioendothelioma (PEH) is a rare vascular neoplasm, predominantly encountered in women, more often in the age group of 40 years and below. It is a tumor of borderline malignant potential with a clinical course intermediate between hemangioma and angiosarcoma. The tumor has variable prognosis, and treatment options include surgical excision in operable cases and chemotherapy in disseminated ones. The present report describes complete clinical, radiological, and histopathological features of PEH with osteoclast‑like giant cells and metaplastic ossification in a 20‑year‑old boy who presented with dyspnea and episodes of hemoptysis with review of literature.

Human papillomavirus (HPV) genome status & cervical cancer outcome - A retrospective study.

Background & objectives: Persistent infections with high-risk (HR) human papillomaviruses such as HPV 16, 18, 31, 33 and 45 have been identified as the major aetiological factor for cervical cancer. The clinical outcome of the disease is often determined by viral factors such as viral load, physical status and oncogene expression. The aim of the present study was to evaluate the impact of such factors on clinical outcome in HPV16 positive, locally advanced cervical cancer cases. Methods: One hundred and thirty two pretreatment cervical tumour biopsies were selected from patients undergoing radiotherapy alone (n=63) or concomitant chemo-radiation (n=69). All the samples were positive for HPV 16. Quantitative real time-PCR was carried out to determine viral load and oncogene expression. Physical status of the virus was determined for all the samples by the ratio of E2copies/E7copies; while in 73 cases, the status was reanalyzed by more sensitive APOT (amplification of papillomavirus oncogene transcripts) assay. Univariate analysis of recurrence free survival was carried out using Kaplan-Meier method and for multivariate analysis the Cox proportional hazard model was used. Results: The median viral load was 19.4 (IQR, 1.9- 69.3), with viral integration observed in 86 per cent cases by combination of the two methodologies. Both univariate and multivariate analyses identified viral physical status as a good predictor of clinical outcome following radiation treatment, with episomal form being associated with increased recurrence free survival. Interpretation & conclusions: The present study results showed that viral physical status might act as an important prognostic factor in 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 identifi ed. 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.

Mesonephric adenocarcinoma (endometrioid type) of endocervix with diffuse mesonephric hyperplasia involving cervical wall and myometrium: An unusual case report.

Malignant mesonephric tumors are rare variants of cervical adenocarcinoma, derived from remnants of mesonephric ducts and are associated with mesonephric remnants and/or mesonephric hyperplasia. Few cases have been described in literature. We report an unusual case of cervical mesonephric adenocarcinoma of endometrioid type with squamous morules in association with diffuse mesonephric hyperplasia involving the cervical walls and extending into the myometrium.

Clinicopathological spectrum of 19 adenosarcomas of female genital tract, including uncommon clinical associations and immunohistochemical profile, reviewed at a single institution.

Background: Adenosarcomas of the female genital tract have been rarely documented as case series from our continent. Materials and Methods: Over a seven-year period, 19 adenosarcomas were critically reviewed. Results: Nineteen tumors occurred in the age range of 21-65 years (mean: 43), in the endometrium (8), endometrium and cervix (4), cervix (4), and ovary (3). Four cases displayed coexisting leiomyomas; two, adenomyosis; two on background endometriosis; and one in post-treated cervix carcinoma. Histopathologically, the tumors were low grade (10; 52.6%) and high grade (9; 47.3%), the latter with sarcomatous overgrowth (SO) (7/9 cases). Dedifferentiation (8, 42.1%) and conspicuous decidualization (2) were noted. Immunohistochemically, the tumors focally expressed CD10 (4/6), smooth muscle actin (SMA) (3/8), desmin (8/11); diffuse vimentin (7/7), and estrogen receptor/progesterone receptor (ER/PR) (2/4). Ki-67 (6 cases) varied 5-20%. Seventeen patients underwent surgery and four received adjuvant treatment (3/4 high-grade tumors). Five tumors recurred (4 high-grade tumors with SO) and one metastasized. Among 11 patients, five were alive with disease (AWD) (mean: 29.4 months) and six, free of disease (FOD) (mean: 15 months), the latter mostly with low-grade type tumors (83.3% cases). Conclusions: Diverse clinicopathological spectrum was noted within adenosarcomas. Low-grade tumors were less aggressive than high-grade ones, with SO. Immunohistochemically, lower CD10 and ER/PR positivity was noted in high-grade tumors. Surgery formed the mainstay of treatment. Adjuvant treatment was offered in high-grade subtypes, including in tumors with SO.

Are we achieving the benchmark of retrieving 12 lymph nodes in colorectal carcinoma specimens? Experience from a tertiary referral center in India and review of literature.

Introduction: The number of lymph nodes (LNs) retrieved from a specimen of colorectal carcinoma may vary. Factors that can possibly affect LN yield are age of the patient, obesity, location of the tumor, neoadjuvant therapy, surgical technique and pathologist's handling of the specimen. Aim: The aim of our study is to look at lymph node retrieval from colorectal cancer (CRC) specimens in our hands and review the literature. Materials and Methods: From May 2010 to January 2011, a total of 170 colorectal carcinoma cases were operated in our institute. Type of the surgeries, lymph node yield was looked at. Results: There were 103 (60.6%) males and 67 (39.4%) females. The commonest age group was 50-59 years (30.6%). The surgeries included 107 surgeries for rectal carcinoma (63%) and 63 surgeries for colonic carcinoma (37%). Sixty six (38.8%) cases had received preoperative chemoradiotherapy, whereas 104 (61.2%) cases were without adjuvant therapy. The total lymph node positivity (metastatic disease) was 44.7% .The overall mean lymph node yield was 12.68 (range 0-63; median 11). The mean lymph node harvest in the age group < 39 was 15.76 whereas, the lymph node harvest in the group more than 39 years old was 11.90. ( statistically significant; P=0.03). The mean lymph node yield from specimens of rectal cancers (10.30) was lower than the mean lymph node yield from specimens for colonic cancers (16.71);( statistically significant, P<0.01). There was also statistically significant difference between the mean LN yield in chemoradionaiive cases (14.63) and in the cases where neoadjuvant therapy was received, (9.59); P<0.01. Conclusion: Pathologist while assessing a specimen of CRC should aim to retrieve a minimum of 12 LN. Surgical expertise and diligence of the pathologists remain two main alterable factors that can improve this yield. Neoadjuvant or preoperative radiotherapy can yield in less number of nodes.

Immature teratoma of the ovary: A clinicopathological study of 28 cases.

Aim: Immature teratoma (IT) of the ovary represents 1% of all ovarian cancers and 20% of malignant ovarian germ cell tumors. This retrospective study of 28 such cases aims to look at its morphological spectrum and to study the correlation of the grade and stage of the tumor with prognosis. Materials and Methods: A retrospective study of 28 cases of IT of the ovary was done. Neuroepithelium was graded as grade I, II and III according to the standard criteria. The presence of immature mesenchyme was also looked for and similarly graded. Results: The median age for the cases was 19 years and abdominal pain was the commonest symptom. Neuroepithelium was seen in 26 cases (6 were grade I, 13 were grade II, and 7 were grade III); and two showed immature mesenchymal tissue (IM) only. IM was seen in all 28 cases, but no correlation with the grade of the IT of the ovary is found. The follow up is available in 23 cases ranging from 6 months to 78 months (median 33 months). Of these, 13 were stage I, 3 were stage II and 7 were stage III ITs. Out of 23 patients, 17 patients were alive without evidence of disease recurrence during the last follow up. Adverse events in the form of death and local recurrence occurred in 6 patients. One patient died of the disease at 7 months duration from the disease onset (stage III, grade II IT). Conclusion: Morphological spectrum of IT of ovary is varied. Immature mesenchyme was seen in all the cases of IT of ovary and its presence should prompt a careful search for immature neuroepithelium. Stage I IT of ovary has better prognosis. Combination of surgery and chemotherapy can give longer survival even in recurrent disease.

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 5/10hpf 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.