Molecular epidemiological study of microtubule-associated protein-like 4-anaplastic lymphoma kinase fusion gene using immunohistochemistry as a cost effective alternative to fluorescence in situ hybridization for Indian patients with adenocarcinoma lung

Background: With fluorescence in situ hybridization (FISH) as the main-stay for the detection of anaplastic lymphoma kinase (ALK) rearrangements, the ALK Break Apart FISH Probe Kit has become a Food and Drug Association-approved companion diagnostic for targeted therapy with the ALK inhibitor crizotinib in lung cancers. The objective of this molecular epidemiological study was to estimate the prevalence of microtubule-associated protein-like 4-ALK (EML4-ALK) fusion gene using immunohistochemistry (IHC) as a cost effective alternative to FISH for Indian patients with nonsmall-cell cancer (NSCC)-adenocarcinoma, favor adenocarcinoma lung and NSCC- Not otherwise specified (NOS). Materials and Methods: Patients with NSCC-adenocarcinoma, favor adenocarcinoma lung, and nonsmall cell lung cancer-NOS histology were considered for this study. Permission was obtained from the Ethics Committee before the start of the study. Clinical characteristics and treatment details were collected from the patient's medical records. IHC analysis was performed using a Ventana automated immunostainer (Benchmark XT). Detection was performed using OptiView DAB Detection and Amplification Kit. Results: A total of 200 NSCC-adenocarcinoma, favour adenocarcinoma and NSCC-NOS patients were included in the study. There were 122 (61%) men and 78 (39%) women with a median age of 57 years. Of the 200 patients, 43 (21.5%) were nonsmokers and 175 (87.5%) had Stage-IV disease at the time of initial diagnosis. 48 (24%) cases were positive for epidermal growth factor receptor mutations, whereas EML4-ALK fusion gene was present in 27 (13.5%) patients. 25 of the 27 patients with ALK positivity received crizotinib therapy. Conclusions: The incidence of EML4-ALK gene fusions (13.5%) in this Indian population is four-fold high than the previous reported incidences and supports the claim of several recent studies that a relatively new ALK clone, 5A4, and D5F3 from Leica/Novocastra and cell signaling technology/Ventana, respectively can accurately identify ALK rearranged lung adenocarcinoma. The inclusion of IHC for the detection of EML4-ALK gene fusions as a low cost alternative seems justified in low resource setting

Diffuse alveolar hemorrhage (DAH): a rare presentation of metastatic angiosarcoma

Abstract Background Angiosarcoma is an uncommon and highly aggressive malignant tumor. Angiosarcoma presenting as diffuse alveolar hemorrhage (DAH) is rare. Case presentation A young female who presented with history of dyspnea was found to have features of DAH on radiological evaluation. Angiosarcoma was confirmed from the histopathological examination of the underlying lung nodule. Management with the palliative chemotherapy showed clinical improvement, and resolution of changes of DAH on imaging. Conclusion Angiosarcomas are not usually listed in the causes of DAH. It must be considered in the differentials of DAH after ruling out the common causes

Expression of epidermal growth factor receptor, p53, Bcl2, vascular endothelial growth factor, cyclooxygenase-2, cyclin D1, human epidermal receptor-2 and Ki-67: Association with clinicopathological profiles and outcomes in gallbladder carcinoma

Background: The present study observed the expression levels of epidermal growth factor receptor (EGFR), p53, Bcl2, vascular endothelial growth factor (VEGF), cyclooxygenase-2 (cox-2), cyclin D1, human epidermal receptor-2 (HER-2) and Ki-67 in gallbladder carcinoma (GBC) and their association with clinicopathological profiles and disease outcomes. Materials and Methods: Fifty consecutive samples of cholecystectomy/biopsies from GB bed (archived formalin fixed paraffin embedded tissue blocks of different stages of GBC) were included, and patient details related to their demographic profile, investigations, tumor profile, treatment, and follow-up were recorded. Immunohistochemistry was performed to study the expression levels. Results: Overexpression of EGFR, p53, Bcl2, VEGF, cox-2, cyclin D1 and HER-2 was observed as 74%, 44%, 8%, 34%, 66%, 64%, and 4%, respectively. Association of Bcl2 overexpression in mucinous morphology (40%, P = 0.045), cox-2 overexpression in early stage (I/II) tumors (87.5%, P = 0.028) and VEGF overexpression in alive patients (47.1%, P = 0.044) was observed. Co-expression of EGFR and p53 were statistically significant (P = 0.033). Ki-67 labeling index was significantly higher in patients in age group <40 years (P = 0.027), and poorly differentiated tumors (P = 0.023). Advanced disease and poorly differentiated tumors showed a significantly poor median survival (P < 0.05). Conclusion: EGFR, cox-2 and cyclin D1 were largely overexpressed. Advanced tumor stages and poorly differentiated tumors are predictors of poor survival

Case Report-Malignant adenomyoepithelioma of the breast

Malignant adenomyoepithelioma of the breast is a rare tumor characterized by biphasic proliferation of both epithelial and myothelial cells. Here we report a 20-year-old female presented to us with recurrence of a breast lump shortly following lumpectomy. Histopathological examination suggested malignant adenomyoepithelioma. She had undergone modified radical mastectomy, received local radiation to the chest wall and six courses of adriamycin and cyclophosphamide. She remains in complete remission at 18 months follow-up. The present case is rare in several respects. The age of presentation was 20 years, much less than what has been reported. Mammography showed micro-calcifications, thus far not described. In addition, our patient had an exceptionally aggressive tumor that recurred within two months of lumpectomy. This tumor also showed good chemo sensitivity

Radial endobronchial ultrasound for the diagnosis of bronchoscopically invisible lesions: First case series from India

Background: A peripheral, bronchoscopically invisible pulmonary lesion is a diagnostic challenge. Transthoracic needle aspiration has long been the investigation of choice but runs the risk of pneumothorax (up to 44%). Newer technologies like radial endobronchial ultrasound (R-EBUS) offer a safer approach. We present our results of R-EBUS in the diagnosis of bronchoscopically invisible lesions. This is the first large case series from India. Aims: (1) To determine the yield of R-EBUS for the diagnosis of bronchoscopically invisible lesions. (2) To compare the yields of forceps versus cryobiopsies in the diagnosis of these lesions. Setting: Tertiary care cancer center. Design: Prospective study. Methods: Consecutive patients presenting between January and October 2015 with bronchoscopically invisible peripheral pulmonary lesions were included. R-EBUS was used to localize and sample the lesion and the yields were analyzed. Yields of cryo and forceps biopsy were compared where both methods had been used. Data were analyzed using SPSS version 22. Results: A definite diagnosis obtained in 67.3% (37/55) patients with no major complications. No significant difference was found in yield between: (1) small (3 cm) lesions: (46.2% versus 78.6%, P = 0.38). (2) central and adjacent lesions: 61.5% versus 70%. (3) forceps and cryobiopsy (n = 28, 75% versus 67.9% P = 0.562). Conclusions: R-EBUS is a safe procedure in our setting and its yield is comparable to that reported in literature. The yield of central and adjacent lesions and forceps or cryobiopsy appears similar. Further refinements in the technique could improve yield

Clinical outcome study of crizotinib in immunohistochemistry-proven echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase fusion gene among Indian patients with adenocarcinoma lung

Aims: The anaplastic lymphoma kinase (ALK) Break Apart FISH Probe Kit and Ventana anti-ALK (D5F3) CDx immunohistochemistry (IHC) assay are the Food and Drug Administration-approved companion diagnostic for targeted therapy with the ALK inhibitor crizotinib in lung cancers. The aim of this study was to assess the efficacy and safety of twice daily crizotinib tablet (250 mg) in IHC-proven echinoderm microtubule-associated protein-like 4 (EML4)-ALK fusion gene among Indian patients with adenocarcinoma lung in the routine clinical practice. Subjects and Methods: Patients with nonsmall cell lung cancer (NSCLC), adenocarcinoma histology, whose tumors were found to be positive for EML4-ALK fusion gene using IHC, were considered for this study. IHC analysis was performed using a Ventana automated immunostainer (Benchmark XT). Detection was performed using Optiview DAB detection and amplification kit. Results: A total of 25 NSCLC adenocarcinoma patients were included in the study. There were 14 (56%) women and 10 (44%) men with a median age of 53 years. All patients had Stage IV disease at the time of initiation of crizotinib therapy. One patient achieved complete response and 20 achieved response rate (PR) for an overall PR of 84%. The median progression-free survival (PFS) was 11.8 months and median overall survival (OS) was 20.6 months. Two (8%) patients experienced severe hepatotoxicity requiring permanent discontinuation of crizotinib therapy. Conclusions: A very high PR, PFS, and OS achieved in our study population indicates that IHC can accurately identify EML4 ALK fusion gene mutations in lung adenocarcinoma patients who are responsive to ALK inhibitors such as crizotinib. IHC should be considered as a cost-effective alternative to FISH, especially in low-resource countries

Analysis of Spatial Heterogeneity of Responses in Metastatic Sites in Renal Cell Carcinoma Patients Treated with Nivolumab

Background: The purpose was to determine whether tumor response to CPI varies by organ and to characterize response patterns in a group of surgically treated metastatic RCC patients treated with Nivolumab. Methods: A retrospective analysis was undertaken between January 2016 and March 2020 on patients receiving Nivolumab for metastatic RCC, following first-line therapy and having at least one baseline and two follow-up scans. A Fisher&rsquo;s exact test was used to compare categorical variables, and a Kruskal&ndash;Wallis test was used to compare continuous variables. Results: Twenty-one out of thirty patients evaluated were eligible, and they were divided into two groups: responders (n = 11) and non-responders (n = 10). According to all iRECIST standards, 18 (85.7 percent) of the 21 patients had PD (10 patients), PR (3 patients), or SD (8 patients). At baseline, 7, 15, 4, 13, 7, and 7 patients, respectively, had detectable hepatic metastasis and lung, brain, lymph node, soft tissue, and other intra-abdominal metastases; these patients were evaluated for organ-specific response. The ORRs for hepatic metastasis and lung, brain, lymph node, soft tissue, adrenals, and other intraperitoneal metastases were correspondingly 10%, 20%, 35%, 0%, and 25%. In total, 13 (61.9%) of them demonstrated varied responses to CPI therapy, with 6 (28.5%) demonstrating intra-organ differential responses. The lymph nodes (35%) had the best objective response (BOR), followed by the adrenals and peritoneum (both 25%), the brain (20%), and the lung (20%). The response rate was highest in adrenal gland lesions (2/4; 50%), followed by lymph nodes (13/19; 68.4 percent) and liver (5/10; 50%), whereas rates were lowest for lesions in the lung (9/25; 36%), intraperitoneal metastases (1/4; 25%), and brain (1/5; 20%). Conclusions: In renal cell carcinoma, checkpoint inhibitors have a variable response at different metastatic sites, with the best response occurring in lymph nodes and the least occurring in soft tissue