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.

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

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.

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.

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.

Monophasic synovial sarcoma of tongue.

Synovial sarcoma is a well defined morphologic entity extensively researched in literature. Synovial sarcoma displays a wide spectrum of clinical presentations and histologic appearances that may give rise to diagnostic dilemmas. One such unusual site in the head and neck area is the tongue. We report a case of monophasic synovial sarcoma of the tongue in a 22-year-old male. Microscopically, this tumor mimicked a poorly differentiated carcinoma which is more common at this site though the patient was young for this type of tumor. On immunohistochemistry, neoplastic cells were positive for cytokeratin, vimentin, calponin, CD99 and bcl2. Molecular studies - viz. reverse transcriptase polymerase chain reaction revealed a SYT-SSX translocation clinching the diagnosis. This paper highlights the immunohistochemistry profile and SYT-SSX translocation which helped arrive at an accurate diagnosis only because the index of suspicion for a monophasic synovial sarcoma is high.

Primary endobronchial synovial sarcoma confirmed by SYT-SSX1 fusion gene transcript by reverse transcriptase polymerase chain reaction.

Primary sarcomas of lung are rare compared to metastatic sarcomas. Herein, we report a rare case of primary pulmonary synovial sarcoma with polypoid endobronchial growth in a 35-year-old lady who presented with cough and dyspnea. A malignant pulmonary tumor was suspected and left pneumonectomy was performed. Grossly, a non-encapsulated polypoidal endobronchial tumor measuring 6 cm in greatest diameter, with a solid, tan-white cut surface was identified. Microscopically, tumor was characterized by a proliferation of oval to spindle-shaped cells arranged in sheets and fascicles. Focal hemangiopericytomatous pattern was noted. Immunohistochemically, tumor cells were positive for vimentin, BCL-2, MIC-2 and calponin and focally positive for pancytokeratin and epithelial membrane antigen. A subsequent molecular analysis performed using reverse transcriptase-polymerase chain reaction with RNA extracted from paraffin-embedded tissue, revealed SYT/SSX1 fusion gene which confirmed the diagnosis of synovial sarcoma. The utility of immunohistochemistry and molecular techniques in diagnosis of such a rare case is stressed and the relevant literature is discussed.

Localized amyloidosis of the urinary bladder, clinically masquerading as bladder cancer.

Amyloidosis is characterized by extracellular deposition of a proteinaceous, hyaline material. Localized deposition of amyloid in individual organs is uncommon. It can occur in the absence of systemic involvement. Herein, we describe two cases of localized amyloidosis of the urinary bladder, which clinically, radiologically, and on cystoscopy masqueraded as bladder cancer. A diagnosis of amyloidosis in both these cases was ascertained on biopsy, supplemented with special stains.

Clear cell sarcoma of the kidney--a study of seven cases over a period of three years.

Clear cell sarcoma of the kidney (CCSK) can display diverse morphological patterns and mimic various other pediatric renal tumors. An accurate diagnosis of this tumour is important considering the therapeutic and prognostic implications. AIM: The present study was undertaken to describe the various histological patterns of CCSK. The histology of 7 cases and the available case files of CCSK accrued over a period of3 years were reviewed. Immunohistochemical (IHC) stains were performed in 3 cases. The histological patterns observed in this study were classical (observed in 4 cases), epithelioid trabecular, myxoid, palisading and hyaline sclerosis types. IHC revealed reactivity to vimentin and non-reactivity to cytokeratin, desmin, smooth muscle actin, neuron specific enolase (NSE) and S-100 protein. Since CCSK is essentially a histological diagnosis, the importance of an accurate diagnosis of CCSK by a pathologist cannot be overemphasized. This study describes the various histological patterns that can be observed in CCSK.

Renal angiomyolipomas--a study of 18 cases.

Angiomyolipoma is a distinctive neoplasm composed of an intimate admixture of three components, viz. mature adipocytes, smooth muscle cells and blood vessels. This study was undertaken to better define the various morphological patterns of angiomyolipoma and their immunohistochemical profile. The paraffin blocks and slides of 18 cases of renal angiomyolipoma, accessioned over a period of 8 years from Tata Memorial Hospital, were reviewed. There were 2 men and 16 women in the age range of 17 to 68 years. Pre-operative fine needle aspiration cytology (FNAC) was performed in 6 cases, of which 5 were erroneously diagnosed as renal cell carcinomal sarcoma. Histologically, 14 cases revealed conventional histology. The remaining 4 cases were particularly misleading posing diagnostic problems due to variant patterns (leiomyomatous variant-3 cases and epithelioid variant- 1 case). Apart from the usual histology, necrosis, giant cells, and varying degrees of nuclear pleomorphism were present in three of the cases. Immunohistochemistry performed in 16 cases revealed immunoreactivity for HMB45 in all the 16 tumors (100%), estrogen receptor (ER) and progesterone receptor ((PR) in 2 cases (12.5%) and 6 cases (37.5%) respectively.

Modified H & E staining technique for fine needle aspiration cytology (FNAC) smears.

Papanicolaou (Pap) staining procedure has achieved worldwide acceptance in cytology practice due to its crisp cytological details. There are many centres or private laboratories in our country which cannot fulfill the economic requirement of Pap staining and hence employ comparatively cheaper haematoxylin and eosin (H & E) stain. Although routine H & E cannot replace Pap, this study is an attempt to modify H & E staining that would offer comparable diagnostic results. The present study is restricted to FNAC material from palpable lesions i.e.breast and lymph nodes. For this purpose 50 lymph nodes ( LN) and 18 breasts were aspirated. Out of two fixed smears, 1 was stained by Pap technique for routine reporting and other by modified H & E method which was examined and reported by other pathologist, Dr.Sangeeta B.Desai ( SBD) The diagnosis of both the techniques were compared. Emphasis was also given on cytomorphological characteristics. Out of fifty lymph node aspirates from various sites, no diagnostic discrepancy was observed in 46 cases. Three out of 4 had sampling errors whereas, poor nuclear staining was noticed in a single case. Out of eighteen breast aspirates concordant diagnosis was achieved in 16 cases. Out of two discrepant diagnosis 1 was due to sampling error, and the other was an interpretative error. All the cases were confirmed histologically. In conclusion, modified H & E staining is useful for common sites of aspirations of superficial lesions.