Survival outcomes with 12 weeks of adjuvant or neoadjuvant trastuzumab in breast cancer

Background: There is limited access to 1 year of adjuvant trastuzumab in resource-constrained settings. Most randomized studies have failed to prove non-inferiority of shorter durations of adjuvant trastuzumab compared to 1 year However, shorter durations are often used when 1 year is not financially viable. We report the outcomes with 12 weeks of trastuzumab administered as part of curative-intent treatment. Methods: This is a retrospective analysis of patients treated at Tata Memorial Centre, Mumbai, a tertiary care cancer center in India. Patients with human epidermal growth factor receptor (HER2)-positive early or locally advanced breast cancer who received 12 weeks of adjuvant or neoadjuvant trastuzumab with paclitaxel and four cycles of an anthracycline-based regimen in either sequence, through a patient assistance program between January 2011 and December 2012, were analyzed for disease-free survival (DFS), overall survival (OS), and toxicity. Results: A total of 102 patients were analyzed with a data cutoff in September 2019. The median follow-up was 72 months (range 6–90 months), the median age was 46 (24–65) years, 51 (50%) were postmenopausal, 37 (36%) were hormone receptor-positive, and 61 (60%) had stage-III disease. There were 37 DFS events and 26 had OS events. The 5-year DFS was 66% (95% Confidence Interval [CI] 56–75%) and the OS was 76% (95% CI 67–85%), respectively. Cardiac dysfunction developed in 11 (10.7%) patients. Conclusion: The use of neoadjuvant or adjuvant 12-week trastuzumab-paclitaxel in sequence with four anthracycline-based regimens resulted in acceptable long-term outcomes in a group of patients, most of whom had advanced-stage nonmetastatic breast cancer.

Access to HER2?targeted therapy at a tertiary care center in India: An evolution

Background:In a previous retrospective audit from our institution we reported that patients had limited access to HER2-targeted therapy due to financial constraints. Subsequently, the advent of biosimilar versions of trastuzumab and philanthropic support has potentially changed this situation. Herein, we reanalyzed and reported access to HER2-targeted therapy in a more recent cohort of patients. Methods: Medical records of new breast cancer patients registered in one calendar year were retrospectively reviewed, supplemented by online pharmacy data to extract information on receptor status, use of HER2-targeted therapy, and other relevant variables. Since not all HER2 immunohistochemistry (IHC) 2+ tumors underwent fluorescent in-situ hybridization (FISH) testing, we estimated the probable HER2 amplified from this group based on a FISH amplified fraction in those HER2 2+ tumors who did undergo FISH. Results: Between January 2016 and December 2016, 4717 new BC patients were registered at our institution, of whom 729 (20.04%) had HER2 IHC 3+ tumors while 641 (17.62%) had HER2 IHC 2+ tumors. The final number of HER2 overexpressing/amplified tumors was estimated to be 928 (729 HER2 IHC 3+, 105 known FISH amplified, and 94 estimated FISH amplified), of whom 831 received treatment at our institution. Overall 474 (57.03%, 95% confidence interval [CI] 53.6–60.4) of these 831 patients received trastuzumab for durations ranging from 12 weeks to 12 months in the (neo)adjuvant setting or other durations in metastatic setting compared to 8.61% (95% CI 6.2–11.6) usage of HER2-targeted therapy in the 2008 cohort. Conclusion: Access to HER2-targeted therapy has substantially increased among patients treated at a public hospital in the past decade, likely due to the advent of biosimilars, the use of shorter duration adjuvant regimens, and philanthropic support. However, further efforts are required to achieve universal access to this potentially life-saving treatment.

Efficacy of screening cancer patients at hospital entrance for COVID-19 with a questionnaire and thermal scanning: An audit

Objectives: Although commonly practiced, the accuracy, effectiveness, and safety of screening patients for COVID-19 at hospital entrances is not well documented. Material and Methods: We performed a retrospective analysis of single institution data involving screening patients for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection at hospital entrances by trained health personnel, with thermal scanning and administration of a standard questionnaire eliciting risk factors and symptoms of COVID-19. SARS-CoV-2 positivity among patients screened positive and negative and among personnel involved in screening were estimated. Results: Between May 22, 2020, and July 4, 2020, a total of 20152 patients involving 54955 hospital visits were screened at hospital entrances of whom 668 (3.31%, 95% CI 3.07–3.57) were screened positive for suspected COVID-19 and 19484 (96.69%, 95% CI 96.44–96.93) were screened negative. Among patients screened positive, of the 638 patients with available records, 109 (17.08%, 95% CI 14.24–20.23) were confirmed to be SARS-CoV-2 positive by polymerase chain reaction test, 288 (45.14%, 95% CI 41.23–49.10) were negative, 71 (11.13%, 95% CI 8.79–13.83) were not tested after secondary assessment, and 170 (26.65%, 95% CI 23.25–30.26) patients declined the test. Among screen negative patients, 162 (0.83%, 95% CI 0.71–0.97) were SARS-CoV-2 positive. Of the 104 personnel involved in screening, 03 (2.88%, 95% CI 0.60–8.20) were confirmed to be SARS-CoV-2 positive during study period. Conclusion: Screening patients with a combination of thermal scanning and a standard questionnaire for COVID-19 has a high positive predictive value for detecting this infection with low risk of SARS-COV-2 transmission to the involved health personnel

FISH patterns of ROS1, MET, and ALK with a correlation of ALK immunohistochemistry in lung cancer: a case for introducing ALK immunohistochemistry ‘Equivocal’ interpretation category in the Ventana anti?ALK (D5F3) CDx assay ? A tertiary cancer center experience

Background: Mutations in ROS1, ALK, and MET genes are targetable alterations in non-small cell lung cancer (NSCLC). They can be evaluated by different techniques, most commonly fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC). Methods: We explored the prevalence of ROS1, ALK, MET mutations, discuss clinicopathological associations and FISH signal patterns on 413 consecutive cases of EGFR negative lung carcinoma from March 2016 to April 2017 using FISH for ALK, ROS1, and MET along with ALK (D5F3) IHC. Results: ROS1 gene rearrangement, ALK positivity (IHC and/or FISH), and MET amplification were seen in 18/358 (5%) cases, 76/392 cases (19.4%), and 10/370 (2.7%) cases, respectively. ALK FISH and ALK IHC were positive in 51/300 (17%) and 58/330 cases (17.57%), respectively, while 8/330 (2.4%) cases were ALK IHC “equivocal” of which 3/8 (37.5%) were ALK FISH positive. Of ALK FISH and IHC co-tested cases, 43/238 (18.07%) cases were positive by both techniques, while 15/43 (34.88%) of ALK positive cases showed discordant ALK FISH and IHC results. All ROS1 rearranged and MET amplified cases were adenocarcinoma. Signet ring cell histology was associated with 78.57% likelihood of being either ALK or ROS1 positive. Genomic heterogeneity was seen in 30% of MET amplified cases. Conclusions: ALK/ROS1/MET gene alterations were found in 25.18% of NSCLC cases. An ALK IHC “equivocal” interpretation category should be incorporated into practice. Atypical patterns of ROS1 and genomic heterogeneity need to be evaluated further for any clinical relevance.

Bladder cancer demographics and outcome data from 2013 at a tertiary cancer hospital in India

BACKGROUND: Bladder cancer (BCa) is the ninth most common cancer accounting for 3.9% of all cancer cases as per the Indian Cancer Registry data. There is a scarcity of data on urinary Bca from India. AIM: The aim of this study was to know demographic background, stage distribution, utilization of various treatment modalities, and oncological outcome in Indian patients presenting with bladder cancer to a tertiary care cancer center in Mumbai. METHODOLOGY: We performed a retrospective audit of all patients registered as urinary BCa in our hospital from January 1, 2013 to December 31, 2013. Electronic medical records of these patients were checked for most of the information gathered. RESULTS: Median age of patients at presentation was 59 years with a range of 18–88 years. There were 84% male and 16% female patients. Forty seven percent of patients had nonmuscle invasive bladder cancer (NMIBC), 36% had muscle invasive bladder cancer and locally advanced disease, and 17% had metastatic disease. Eight patients were treated with trimodality bladder preservation protocol. Recurrence was seen in 38 (22.6%) patients with NMIBC. Out of them. 44.7% and 55.3% were in low- and high-grade tumors, respectively. Overall survival and disease-free survival estimated for 3 years were 63% and 57%, respectively. CONCLUSION: Bladder cancer has a varied spectrum of presentation. Bladder cancer patients presenting to our hospital generally have a higher stage and grade of disease compared with that in the west.

Breast cancer in a tertiary cancer center in India - An audit, with outcome analysis

Background: Surgery is the mainstay in the management of thyroid cancer. Surgical outcomes need to be tempered against the excellent prognosis of the disease. Aims: This study aims to study the surgical outcomes including the 30-day morbidity and 5-year survival of thyroid cancer patients. Settings and Design: Retrospective analysis of a prospectively maintained surgical database in a tertiary cancer center in India. Materials and Methods: We analyzed 221 surgically treated patients in the year 2012. Statistical Analysis: Used IBM SPSS 24.0 (Armonk, NY) with p < 0.05. Results: The median age was 40 years with predominantly papillary thyroid carcinoma (55%). Localized disease in 47% of cases, locoregional disease in 42.5% and distant metastasis in 10.2% of cases at presentation was noted. Treatment naïve patients were 71% and revision surgeries were done in 29% patients. Extended thyroidectomy constituted 11% of the surgeries. Temporary hypocalcemia was seen in 30.8% of patients, 5% requiring intravenous calcium supplementation. Vocal cord palsy as per nerve at risk and chyle leak were seen in 4.5% and 3.1%, respectively. Aggressive histology, extended thyroidectomy, and inadvertent parathyroidectomy were significant factors associated with complications. Five year estimated overall survival with median follow-up of 50 months was 98%, and event-free survival was 84.8%. Advanced age, distant metastasis at presentation and aggressive histology connoted poor outcomes. Conclusion: Thyroid cancer, irrespective of the extent of disease, has good prognosis. Aggressive histology, the extent of thyroid surgery, distant metastasis and age are important factors, which should be factored in the algorithm of thyroid cancer management.

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.

Pseudopapillary prostatic adenocarcinoma: A diagnostic pitfall for pathologists.

Prostatic adenocarcinoma and urothelial carcinoma are common tumours seen in elderly patients. They both act as a close differential diagnosis for each other clinically as well as histologically. Various morphological patterns have been described in prostatic adenocarcinomas. However, pseudopapillary pattern was not described until recently a paper which described seven such cases. These tumours mimic urothelial carcinoma as the papillary pattern is usually seen in urothelial carcinoma and may act as a pitfall for the diagnosing pathologists. As both the tumours are treated with different therapeutic protocol it is necessary to differentiate the two and hence the pathologist should be aware of this morphological variant of prostatic carcinoma. Critical histological review and immunohistochemical examination is helpful to make the diagnosis. Here we discuss one such case of pseudopapillary prostatic adenocarcinoma mimicking urothelial carcinoma with a brief review of histological and immunohistochemical examination useful to distinguish the two tumours.

Granulosa cell tumor of testis: Clinicopathological correlation of a rare tumor.

Background: Granulosa cell tumor of testis is a rare tumor accounting for less than 4% of adult testicular tumors though they account for nearly 30% of childhood testicular tumors. Due to the rarity of these tumors, exact etiology, pathogenesis, prognostic factors and best treatment approach are not well known. The molecular events in pathogenesis of these stromal tumors have begun to unravel and these developments put forth a reasonable and scientifi c explanation for the association of these tumors with developmental anomalies like undescended testis. However, many questions remain unanswered. Materials and Methods: We performed a retrospective analysis of clinicopathological features of all Granulosa Cell Tumors of testis from our archives in addition to an extensive literature search using PUBMED with the key words “Granulosa Cell Tumor, testis”. Results: We found six cases in our archives, two of which were of juvenile type and four of adult type. One out of these six cases presented with metastases. All cases underwent radical orchidectomy. Morphology and immunohistochemistry were classical in all cases and there was no diagnostic dilemma. Literature search revealed 63 cases of testicular Granulosa Cell Tumor in addition to highlighting the similarities in the biology and the dissimilarities in the clinical behavior as compared to ovarian Granulosa Cell Tumor. Conclusion: Testicular Granulosa Cell Tumor is a rare tumor, which although histologically similar to its ovarian counterpart, differs in clinical behavior. Further detailed investigations are needed to reveal the mystery behind the differing clinical behavior despite histological and immunohistochemical similarity between the testicular and ovarian Granulosa Cell Tumors.

Response to article titled "US-funded measurements of cervical cancer death rates in India: scientific and ethical concerns" by Eric J Suba.

Dr Eric Suba has been distorting facts and persistently disseminating biased and misleading views and statements regarding our studies over the past several years. His article in the Indian Journal of Medical Ethics fails to mention the facts that seem unfavourable to his arguments, and the ethical concerns are unsubstantiated by the evidence. In this context, we present the following clarifications for the attention of your readers, notably with regard to: (i) the study design and inclusion of a control group; (ii) the informed consent of the women participating in the study; (iii) the conformity with international ethical standards and guidelines, and (iv) the provision of screening to women in the control arm of the studies. We also highlight the benefits that are flowing from this research and the risk that misinformation may further delay access for women to life-saving cervical cancer screening.

Paraganglioma of the urinary bladder: A clinicopathologic spectrum of a series of 14 cases emphasizing diagnostic dilemmas.

Background: Paraganglioma (PG) of the urinary bladder is a rare neuroendocrine neoplasm, accounting for < 0.1% of all bladder tumours. Distinction from urothelial carcinoma is imperative as management and prognosis vary markedly. In this report, we describe our experience with the histopathology of paragangliomas of the urinary bladder with emphasis on the histologic features that have led to their being misdiagnosed as conventional urothelial cancer and, most importantly, those that will help pathologists recognize this rare tumor of the bladder. Materials and Methods: All cases of PG of urinary bladder diagnosed at our institute from 2002-2012 were retrieved and diagnosis confi rmed in accordance with WHO classifi cation. Clinical and treatment details were obtained from hospital medical records. Results: Fourteen cases of PG of urinary bladder including 5 consult cases were analysed. These included 11 transurethral resections ± partial cystectomies, 2 partial cystectomies and 1 radical cystectomy. Two out of the 5 consult cases had been submitted with a diagnosis of urothelial carcinoma and 1 with that of a rhabdomyosarcoma. Age ranged from 15-84 years (median, 43 years) with a male to female ratio of 1:2.5. Presenting symptoms were haematuria, dysuria and fl ank pain; only 1 case had antecedent hypertension. Histologically, typical ‘zellballen’ (72%), diffuse (21%) and ribbon-like (7%) growth patterns amidst a richly vascularised stroma were seen. Muscularis propria invasion and necrosis was present in 72% and 21%, respectively. Substantial cautery artifacts led to misdiagnosis in the 3 erroneous cases. Tumour cells were positive for chromogranin, synaptophysin; sustentacular cells were S-100 positive. Follow up was available in 6 patients; median follow-up was 29 months (8-120 months). One patient developed distant metastasis in cervical lymph node 10 years after diagnosis; remaining were alive without evidence of disease. Conclusions: Paraganglioma of the urinary bladder is a rare tumor and may be misdiagnosed as urothelial cancer especially on TURBT, but a high index of suspicion, careful search for the characteristic histological features and supportive immunohistochemical studies should lead to a correct diagnosis

Immunohistochemical validation of TLE1, a novel marker, for synovial sarcomas.

Background & objectives: Logistic and financial constraints limit application of several available immunohistochemical (IHC) markers and molecular analysis in every case of synovial sarcoma, diagnosed in our settings. Recently, TLE1 has been recognized as a robust IHC marker for diagnosing a synovial sarcoma. Here, we present IHC features of synovial sarcomas, including TLE1 expression in these cases and in some other tumours. Methods: Conventional sections from 42 synovial sarcomas (30 retrospective & 12 prospectively diagnosed) were subjected to TLE1 IHC staining, including 21 tumours confirmed with molecular testing. TLE1 immunostaining was graded from 0, 1+, 2+, 3+, with 2+ or 3+ grades interpreted as positive staining. Results: Of the 42 tumours, 26 (61.9%) were of monophasic spindle cell type, 13 biphasic type (30.9%), two (4.7%) calcifying type and remaining one (2.3%) was a poorly differentiated synovial sarcoma. On immunohistochemistry (IHC), tumours were positive for epithelial membrane antigen (EMA) (26/34, 76.4%), cytokeratin (CK)7 (6/10, 60%), CK/MNF116 (6/21, 28.6%), B cell lymphoma 2 (BCL2) (36/37, 97.3%), cluster of differentiation molecule 99 (MIC2) (23/31, 74.1%) and transducin-like enhancer of split 1 (TLE1) (40/42, 95.2%), while negative for CD34 in all 21 tumours, wherever performed. TLE1 was also positive in tumour controls, including schwannomas (5/5, 100%), neurofibromas (2/2, 100%), malignant peripheral nerve sheath tumors (2/12, 17%) and Ewing sarcomas (4/10, 40%). TLE1 sensitivity for diagnosis of synovial sarcomas was 95.2 per cent. Its overall specificity was 63.7 per cent, whereas with regards to tumors forming its closest differential diagnoses, its specificity was 72 per cent. Interpretation & conclusions: Although molecular confirmation is the diagnostic gold standard for synovial sarcoma, TLE1, in view of its high sensitivity may be a useful marker within the optimal IHC panel comprising EMA, BCL2, MIC2, CD34 and CK7, especially on small biopsy samples, for substantiating a diagnosis of synovial sarcoma. Awareness of TLE1 expression in other tumours and its correct interpretation are necessary.

Retroperitoneal sclerosing PEComa with melanin pigmentation and granulomatous inflammation-A rare association within an uncommon tumor.

PEComa, defined as a perivascular epithelioid cell tumor, displays a wide clinicopathological spectrum. Lately, a sclerosing PEComa has been identified as its distinct variant, but with limited documentation, in view of its rarity. Herein, we describe an uncommon case of a 53-year-old lady, who was referred to us with pain abdomen. Radiological imaging disclosed a well-defined, hypodense retroperitoneal mass. The excised tumor was a round, encapsulated soft tissue mass measuring 7 cm with a tan-brown cut surface. Microscopy showed uniform, epithelioid cells with clear cytoplasm, focal melanin pigmentation and mild nuclear atypia, arranged in sheets and nests around capillary-sized vessels in a dense sclerotic stroma. Additionally, co-existing epithelioid granulomas were noted. On immunohistochemistry (IHC), tumor cells were diffusely positive for HMB45; focally for desmin and smooth muscle actin (SMA), while negative for EMA, CD10, S100-P, Melan A, CD34, AMACR and CK MNF116. This case reinforces sclerosing PEComa as an uncommon, but a distinct clinicopathological entity and exemplifies diagnostic challenge associated with it; necessitating application of IHC markers for its correct identification. Presence of melanin pigment and granulomatous inflammation in the present tumor constitute as novel histopathological findings in a sclerosing PEComa.

HER 2 status in invasive breast cancer: Immunohistochemistry, fluorescence in-situ hybridization and chromogenic in-situ hybridization.

Introduction : HER2/neu gene status in breast cancers can be evaluated by targeting protein and gene - immunohistochemistry (IHC) and fluorescence in-situ hybridization (FISH). Recent studies have shown chromogenic in-situ hybridization (CISH) as a relatively cheaper alternative. Materials and Methods : Forty-three nonconsecutive, randomly selected primary invasive breast cancer cases were evaluated for c-erbB-2 (HER2 protein) by IHC and gene amplification by FISH and CISH. Results of each of the same were compared. Results : CISH showed approximately 90% and 100% concordance for IHC negative and positive cases, respectively; while approximately 94.4% and 91% concordance with FISH amplified and non-amplified cases, respectively. Conclusion : This study showed feasibility of incorporation of CISH as a low cost option in routine management of breast carcinoma in the Indian setting. Secondly, reconfirmation of IHC negative and positive cases can be done by CISH.

Epithelioid malignant mesothelioma of tunica vaginalis with deciduoid features: An unusual malignancy clinically masquerading an inguinal hernia.

Paratesticular/scrotal and inguinal canal mass lesions in elderly patients may pose a diagnostic challenge to both the surgeon as well as the pathologist. In most cases, these represent hernial sacs with their contents, and true neoplasms like lipomas, rhabdomyosarcomas, and fibrous pseudotumors are infrequent. Malignant mesotheliomas arising from the tunica layers are rare cause of inguinal and paratesticular tumors. Herein, we report a case of an elderly patient who presented with an inguinal hernia which pathologically had features of deciduoid malignant mesothelioma.

Composite epithelial kidney tumor comprising of adeno and neuroendocrine carcinomatous components: An unusual variant of renal cell carcinoma.

Renal cell carcinomas accounts for an approximately 2% of human malignancies with atleast ten different histological subtypes recognized by the World Health Organization (WHO) 2004 classification. Composite carcinomas with dual divergent epithelial differentiation in kidneys are extremely uncommon. We report an unusual case of a 37-year-old female who presented with symptoms related to renal tumor for the last three years. Computed tomography scan revealed a large heterogenously contrast enhancing left kidney mass comprising of two distinct histological components of low grade adenocarcinomatous and carcinoid-like low grade neuroendocrine carcinomas with presence of hilar lymph nodal metastases of both the components. The component of adenocarcinoma was immunoreactive to E-cadherin, cytokeratins 7 and 19 with negativity for cluster of differentiation 10, cytokeratin 20, CD117, and vimentin; while the neuroendocrine component was immunoreactive for vimentin, chromogranin and synaptophysin with negativity for CD10, CD117, and cytokeratins 7, 19 and 20. MIB-1 labeling index in the both the components was 2-3%. The present case is the first of its kind to be reported in the kidney and emphasizes the diversity potential of kidney tumors.

Tubulocystic carcinoma of kidney associated with papillary renal cell carcinoma.

Tubulocystic renal cell carcinoma (TCRCC) is a rare variant of renal cell carcinoma, which has distinct histology but there is some controversy about its association with papillary renal cell carcinoma (PRCC) and cell of origin in literature. We report an 18-year-old girl with the rare TCRCC of kidney associated with PRCC with metastases to the para-aortic nodes. The patient presented with hematuria and a right renal mass with enlarged regional nodes for which a radical nephrectomy with retroperitoneal lymph node dissection was done. On gross examination, a solid cystic lesion involving the lower pole and middle pole of the kidney measuring 12x9x9 cm was seen along with an additional cystic lesion in upper pole of kidney. Microscopically the main tumor showed the typical histology of a tubulocystic carcinoma with multiple cysts filled with secretions lined by variably flattened epithelium with hobnailing of cells. The mass in the upper pole was a high-grade PRCC and the nodal metastases had morphology similar to this component. To conclude, at least a small but definite subset of TCRCC is associated with PRCC, and cases associated with PRCC do seem to have a higher propensity for nodal metastasis as in the case we report.

Assessment of HER-2/neu status in breast cancer using fluorescence in situ hybridization & immunohistochemistry: Experience of a tertiary cancer referral centre in India.

Background & objective: Determination of HER2 status in breast cancer has become important to identify potential candidates for anti-HER2 therapy. In this study we compared fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC) for the determination of HER2 status in breast cancer patients referred to a tertiary care referral centre. Methods: A total of 200 cases of invasive breast cancer were evaluated for HER2 status using IHC and FISH and results were compared. Results: The IHC 3+ (93.9%) and IHC negative (85.9%) cases showed good concordance with the corresponding FISH results; while 66.6 per cent of IHC 2+ cases showed gene amplification by FISH. In addition, hormone receptor expression and HER2 gene status showed a statistically significant inverse association (P<0.05). Interpretation & conclusion: These findings reaffirm IHC as a prudent first-step to screen tissue samples for HER2 status and to determine suitability for technically demanding FISH test and the dual coloured FISH as a gold standard for determination of HER2/neu status in IHC equivocal cases of breast carcinoma.