Pure intertubular seminoma (PITS) of the testis: A multi-institutional cohort of a rare growth pattern of seminoma.

Pure intertubular seminoma (PITS) of the testis is described as the presence of seminoma cells within the interstitium of testis without any evidence of diffuse growth pattern or mass lesion of classical seminoma. These tumors are clinically and grossly inconspicuous and are diagnosed incidentally or during investigations for testicular pain, infertility or other symptoms. Rarely metastasis is the first presentation. Microscopic identification can be difficult and poses a diagnostic challenge in the absence of a mass lesion. Seminomas with exclusive intertubular growth patterns were gathered in an international cohort. Diagnoses were confirmed by fellowship-trained or specialized urologic pathologists. Cases with the presence of a classical diffuse or nested pattern of seminoma or any other germ cell tumor component were excluded. The patient's age, tumor characteristics and additional clinicopathologic features were recorded and analyzed. 15 patients of pure intertubular seminoma (PITS) were collated. The mean age of presentation was 29 years. Patients presented with variable symptoms, including undescended testis (26%, n = 4/15), testicular heaviness/pain (20%, n = 3/15) infertility (20%, n = 3/15) and metastasis (6%, n = 1/15); presentation was unknown in 4 patients. Of note, none of the patients presented because of testicular mass. Serum markers were within normal limits in most patients (93%, n = 14/15) with available data. No tumors were identified macroscopically; however, an ill-defined, grey-white, firm area was noted in one orchiectomy specimen. Microscopically, tumor cells were seen in intertubular spaces as dispersed individual cells or small clusters. Tumor cells were round to polygonal with large nuclei and prominent nucleoli. Mild to moderate lymphocytic infiltrates were seen admixed with tumor cells in 40% (n = 6/15) of the tumors. GCNIS was present in association with most PITS (73%, n = 11/15). Tubular atrophy with thickening of the basement membrane and Leydig cell hyperplasia was observed in one tumor. Thirty-three percent (n = 5/15) of the tumors showed pagetoid involvement of rete testis, including the tumor with metastasis. All tumors showed the classical immunohistochemical profile of seminoma, with PLAP, c-KIT, OCT3/4, D2-40 and SALL4 positivity. PITS can be clinically & pathologically inconspicuous, difficult to stage and liable to be misdiagnosed especially if presented with metastasis. Despite the inconspicuousness, PITS may represent an aggressive growth pattern of seminoma with the propensity for rete testis invasion.

Real-World Data on Treatment Outcome of ALK-Positive Non-Small Cell Lung Cancer from an Indian Multicentric Cancer Registry.

Lalatendu Moharana The Anaplastic lymphoma kinase inhibitors (ALKi) represent the standard of care for metastatic non-small cell lung cancer (NSCLC) patients with EML4-ALK rearrangements. Various ALKi agents are available; however, not all eligible patients receive treatment with them due to various reasons. Given the limited real-world data available in our country, we aimed to assess treatment outcomes through a multicenter collaboration. This retrospective, multi-institutional study was conducted under the Network of Oncology Clinical Trials India and included a total of 67 ALK-positive metastatic lung cancer patients from 10 institutes across India, with a median follow-up of 23 months. In the first line setting, the objective response rate (ORR) with ALKi was 63.6% (crizotinib: 60.7%, ceritinib: 70%, alectinib: 66.6%, p = 0.508), while with chemotherapy, it was 26.1%. The median progression-free survival (mPFS) for the first line ALKi group was significantly higher than that for chemotherapy (19 vs. 9 months, p = 0.00, hazard ratio [HR] = 0.30, 95% confidence interval [CI]: 0.17-0.54). The mPFS for crizotinib, alectinib, and ceritinib was 17, 22, and 19 months, respectively ( p = 0.48). Patients who received ALKi upfront or after 1 to 3 cycles of chemotherapy or after 4 or more cycles of chemotherapy had mPFS of 16, 22, and 23 months, respectively ( p = 0.47). ALKi showed superior mPFS compared to chemotherapy in the second line (14 vs. 5 months; p = 0.002) and the third line (20 vs. 4 months; p = 0.009). The median overall survival (OS) was significantly better in patients who received ALKi in any line of therapy (44 vs. 14 months, p < 0.001, HR = 0.10, 95% CI: 0.04-0.23). Brain progression was higher among those who did not receive ALKi (69.2 vs. 31.5%). In conclusion, the use of ALKi as first line treatment for ALK-positive metastatic NSCLC patients resulted in improved PFS. PFS and ORR did not significantly differ between patients who received ALKi upfront or after initiating chemotherapy. Notably, patients who received ALKi in second or later lines demonstrated significantly better outcomes compared to those receiving chemotherapy. The use of ALKi in any line of therapy was associated with significantly prolonged OS.

Adolescent and Young Adults with Gastric Cancer (AYA-GC)-The Dilemma of an Under-Represented Group: A Multi-Institutional Analysis from the Indian Subcontinent.

Soumya Surath PandaGastric cancer (GC) is often ignored at a young age, which frequently leads to tragic consequences. The worldwide incidence of GC is increasing at a young age. In view of the limited Indian publication, we sought to characterize clinicopathological parameters and risk factors in the adolescents and young adults (AYA) population. Retrospective data from six centers (which are part of the Network of Oncology Clinical Trials in India) from 2015 to 2020 were collected from patient (18-39 years of age) records. This study was approved by the institutional ethical committee of individual centers. All statistical analyses were performed using Microsoft Excel and SPSS (Version 20). Data interpretation along with the analysis of obtained results was carried out using the following tests: Qualitative data was expressed in terms of frequency/percentage. One-hundred fifty-two AYA GC patients were enrolled. The 31 to 39 years age group was most affected in which 76.3% were females. The majority of patients were nonalcoholic (93.4%), nonsmokers (98.0%), and without a family history (98.0%). The most common (MC) presenting symptom was abdominal pain (67.1%). MC site was antrum (48%). Among esophagogastric junction cancers, the majority were type I and II Siewert classifications (77% [20/26] patients in cardia), MC histology-signet ring cell (67.1%) followed by diffuse-type (65.1%). Most were poorly differentiated (65.1%) and were diagnosed at an advanced stage (III & IV= 54.6%). This is one of our country's first large multicenter studies on GC in the AYA population. There was a higher female prevalence, aggressive tumor behavior and the majority of patients were diagnosed at a more advanced stage. The majority were nonsmokers with a negative family history. Awareness among general people, researchers, clinicians, and policymakers must be improved to better the loss of life years in the younger population.

Clinicopathologic Profile and Treatment Outcomes of Colorectal Cancer in Young Adults: A Multicenter Study From India.

PURPOSE: Colorectal cancer (CRC) in young adults is a rising concern in developing countries such as India. This study investigates clinicopathologic profiles, treatment patterns, and outcomes of CRC in young adults, focusing on adolescent and young adult (AYA) CRC in a low- and middle-income country (LMIC). METHODS: A retrospective registry study from January 2018 to December 2020 involved 126 young adults (age 40 years and younger) with CRC. Patient demographics, clinical features, tumor characteristics, treatment modalities, and survival outcomes were analyzed after obtaining institutional ethics committees' approval. RESULTS: Among 126 AYA patients, 62.70% had colon cancer and 37.30% had rectal cancer. Most patients (67%) were age 30-39 years, with no significant gender predisposition. Females had higher metastatic burden. Abdominal pain with obstruction features was common. Adenocarcinoma (65%) with signet ring differentiation (26%) suggested aggressive behavior. Limited access to molecular testing hindered mutation identification. Capecitabine-based chemotherapy was favored because of logistical constraints. Adjuvant therapy showed comparable recurrence-free survival in young adults and older patients. For localized colon cancer, the 2-year median progression-free survival was 74%, and for localized rectal cancer, it was 18 months. Palliative therapy resulted in a median overall survival of 33 months (95% CI, 18 to 47). Limited access to targeted agents affected treatment options, with only 27.5% of patients with metastatic disease receiving them. Chemotherapy was generally well tolerated, with hematologic side effect being most common. CONCLUSION: This collaborative study in an LMIC offers crucial insights into CRC in AYA patients in India. Differences in disease characteristics, treatment patterns, and limited access to targeted agents highlight the need for further research and resource allocation to improve outcomes in this population.

Practical Consensus Guidelines for the Use of S-1 in GI Malignancies.

Purvish M ParikhS-1 (5-fluorouracil prodrug [tegafur] in combination with 5-chloro-2,4-dihydroxypyridine [CDHP] and potassium oxonate [OXO]) was first approved in 1999. In order to make it easy for community oncologists, we decided to put together this expert consensus guideline for its use in gastrointestinal (GI) malignancies. A total of 15 subject matter experts used modified Delphi method to discuss, analyze, and vote on key aspects regarding practical approach to use of S-1 in GI cancers, a process involving 6 months of work. The consensus guidelines specify how S-1 use can be optimized in patients with colorectal, gastric, and pancreatic tumors. The voting for the 17 key points resulted in a majority consensus for all the statements (approval ranging from 13/15 [87%] to 15/15 [100%]). S-1 is a combination of three drugs (tegafur, CDHP, and OXO) specifically designed to reduce toxicity and enhance efficacy; clinical data and meta-analysis confirm both factors; and it is recommended as standard of care for GI cancers. S-1 is approved and one of the standards of care for all lines of therapy in colorectal cancer and pancreatic cancers. S-1 with oxaliplatin is the standard of care for gastric cancers.

PD-L1 expression in head and neck squamous cell carcinoma and its clinical significance: A prospective observational study from a tertiary care centre.

BACKGROUND: Programmed Death Ligand 1 (PD-L1) expression in tumor cells contribute to tumor immunity and therapies directed against it, have shown encouraging results in recent years. As there is limited data on the significance of PD-L1 expression in Head and Neck Squamous Cell Carcinoma (HNSCC) from India, we aimed to study the PD-L1 expression and its relation with different clinic-pathological parameters in patients of HNSCC from a tertiary care center in Eastern India. METHODS: A prospective evaluation of HNSCC patients diagnosed and managed at our center over a period of two and half years, was performed. PD-L1 expression in formalin fixed-paraffin embedded tumor tissue specimens was measured using SP-263 (Ventana) and 22C3 (Dako). A PD-L1 expression of <1%, 1-19%, ≥20% were considered negative, low, and high expression, respectively, and was correlated with various parameters. RESULTS: A total of 71 patients (mean age 50.8 ± 13.3 years, 86% males) were diagnosed with HNSCC (buccal mucosa-28, tongue-22, rest of oral cavity-8, larynx-7, nasopharynx-6). The tumor was poorly differentiated in 12 (17%). PD-L1 positivity was seen in a total of 51 (71.8%) patients (1-19%:18, ≥20%:33). Thirty (85.7%) patients among those aged <50 years and 58.3% of those aged ≥50 years showed PD-L1 positivity which was significant (P = 0.01). There were no statistically significant differences in PD-L1 positivity with respect to gender, tobacco use, tumor grade as well as tumor and nodal stage. Median follow up duration was 18 months (range 3-31 months) and there was significant difference in overall survival among PD-L1 positive and negative groups (31 vs 24 months; log rank P = 0.03). CONCLUSIONS: 72% of HNSCC patients in our cohort showed PD-L1 positivity and it was not associated with any patient demographic characteristics or aggressive pathological features. Positive PD-L1 expression may have a beneficial effect on overall survival in HNSCC.

PD-L1 expression and its significance in advanced NSCLC: real-world experience from a tertiary care center.

BACKGROUND: Targeted therapies against programmed death ligand-1 (PD-L1) in non-small cell lung cancer (NSCLC) have revolutionized the management in recent years. There is paucity of data on the significance of PD-L1 expression in NSCLC from India. We aimed to study the prevalence of PD-L1 expression and its relation with different clinico-pathological parameters in advanced NSCLC from a tertiary care center in Eastern India. METHODS: All consecutive patients with advanced NSCLC diagnosed from January 2020 to December 2021 were prospectively evaluated for PD-L1 expression in formalin fixed-paraffin embedded tumor tissue specimens using immunohistochemistry analysis. A PD-L1 expression of < 1%, 1-49%, and ≥ 50% were considered negative, low, and high expression positive respectively, and association with various parameters was performed. RESULTS: Out of the 94 patients (mean age 59.6 ± 14 years and 63.8% males), PD-L1 positivity was seen in 42 (44.7%) patients, with low positivity (1-49%) in 29 patients and high positivity (≥ 50%) in 13 patients. Epidermal Growth Factor Receptor (EGFR) mutations were seen in 28 patients (29.8%). There were no significant differences in PD-L1 positivity with respect to gender, age, and molecular mutation status. PD-L1 positivity was significantly associated with tobacco use (p = 0.04), advanced tumor stage (p < 0.001), and higher nodal stage (p < 0.001). Median overall survival in the cohort was 17 months and it was not significantly different between the PD-L1 positive and negative groups. CONCLUSIONS: Forty-five percent of advanced NSCLC patients in our cohort showed positive PD-L1 expression and it is associated with tobacco use and aggressive tumor characteristics.

Management and outcome of EGFR mutant lung cancer with SARS-CoV-2 infection.

The world and India, in particular, have been grappling with the coronavirus disease (COVID-19) pandemic for more than a year now. The simultaneous presence of active COVID-19 infection with lung cancer poses both a diagnostic and therapeutic dilemma, because of similar clinical, radiological features along with increased susceptibility to ICU admissions and death. We present the case of a metastatic EGFR mutant lung cancer patient who was started on Gefitinib during active COVID-19 infection. He had made a complete recovery from COVID-19 infection while achieving a partial response to therapy in terms of primary lung cancer. The case highlights the importance of active involvement of a medical oncologist in the care of all cancer patients with COVID-19 infection instead of the traditional holding of all therapy for cancer until COVID-19 recovery as suggested by the majority of guidelines.

Ramucirumab in Indian Patients with Advanced Gastric Cancer-Does Borderline Performance Status and Heavy Burden of Disease in Real World Practice Impact Clinical Benefit?

Vikas OstwalBackground Ramucirumab is considered a standard of care as second-line therapy (CT2) in advanced gastric cancers (AGCs). The aim of this study was to assess practice patterns and outcomes with ramucirumab among Indian patients with AGCs. Materials and Methods A computerized clinical data entry form was formulated by the coordinating center's (Tata Memorial Hospital) medical oncologists and disseminated through personal contacts at academic conferences as well as via email for anonymized patient data entry. The data was analyzed for clinical characteristics, response rates, and survival outcomes. Results A total of 26 physicians contributed data, resulting in 55 patients receiving ramucirumab and being available for analysis. Median age was 53 years (range: 26-78), 69.1% of patients had greater than two sites of disease, and baseline Eastern Cooperative Oncology Group's performance score (ECOG PS) ≥ 2 was seen in 61.8% of patients. Ramucirumab was used as monotherapy in 10.9% of patients, while the remaining 89.1% received ramucirumab combined with chemotherapy. Median event-free survival (EFS) and median overall survival (OS) with ramucirumab were3.53 months (95% CI: 2.5-4.57) and 5.7 months (95% CI: 2.39-9.0), respectively. Common class specific grade adverse events seen with ramucirumab included gastrointestinal (GI) hemorrhage (9.1% - all grades) and uncontrolled hypertension (Grade 3/4 - 3.6%). Conclusions Ramucirumab appears to have similar efficacy in Indian AGC patients when compared with real-world data from other countries in terms of median EFS, but OS appears inferior due to more patients having borderline ECOG PS and high metastatic disease burden. GI hemorrhages appear more common than published data, although not unequivocally related to ramucirumab.

Cutaneous involvement in diffuse large B cell lymphoma at presentation: report of two rare cases and literature review.

BACKGROUND: Diffuse large B cell lymphoma (DLBCL) can occur at nodal and/or extra-nodal sites. After the gastrointestinal tract, cutaneous involvement predominates in extra-nodal DLBCL. Skin involvement at presentation can be in the form of plaques, papules, nodules or ulcers. Differentiating primary cutaneous DLBCL from systemic DLBCL with cutaneous involvement is important for appropriate patient management. CASE PRESENTATION: We describe here, two interesting cases of skin involvement in DLBCL- one primary cutaneous DLBCL and the other, cutaneous involvement in systemic DLBCL with different clinico-pathological profiles. Though both cases had almost similar morphology of the skin lesions (ulcero-proliferative) at presentation, the disease was confined to the skin in the former, while the latter had involvement of lymph nodes and bone marrow. CONCLUSIONS: Meticulous clinical evaluation, appropriate histopathological and immunohistochemical workup helped in their diagnosis and correct classification of the disease status, guiding the further treatment decisions.

Primary gastric Hodgkin's lymphoma: A rare coincidence.

Mostly primary gastric lymphomas are of the non-Hodgkin variety. Primary Hodgkin lymphoma (HL) of the stomach is an unusual entity that may be a big challenge in diagnosis. We reporter are case presenting as gastric outlet obstruction, which was later diagnosed as primary Hodgkin's Lymphoma of the stomach. Its rare coincidence makes it worth to be reported to sensitize clinicians as well as pathologists for the uncommon extra nodal site of Hodgkin's Lymphoma.

Flow Cytometry Based MRD and Its Impact on Survival Outcome in Children and Young Adults with ALL: A Prospective Study from a Tertiary Cancer Centre in Southern India.

Presence of minimal residual disease (MRD) following induction chemotherapy is a well-recognized risk factor to predict relapse in acute lymphoblastic leukemia (ALL). There is paucity of data on MRD and outcome in ALL from India. We share our experience in establishing a flow cytometry-based MRD assay for ALL with emphasis on determination of the number of patients who had MRD on day 35 of induction therapy and its correlation with outcome and other prognostic factors. We prospectively studied MRD in patients with ALL less than 25 years who achieved morphological complete remission with induction therapy. The initial series consisted of 104 patients with ALL. Ninety-two patients had bone marrow samples collected on day 35 of remission induction chemotherapy that was adequate for MRD. Strategy of monitoring MRD was based on flow cytometry using six color staining according the leukemia associated immunophenotype found at diagnosis. Data analysis was done using Fisher exact test. The median age was 8.5 years (range 0.9-22 years). Thirty-seven out of ninety-two patients (40.2%) had MRD at end of induction. MRD on day 35 was between 0.01 and 0.1% in 18.9% of patients, between 0.1 and 1% in 59.5% and more than 1% in 21.6% patients. Among the patients who had MRD, 16.7% had favourable cytogenetics, 60% had intermediate and 13.3% had high-risk cytogenetics. The presence or absence of residual leukemia by flow cytometry at day 35 was not significantly related to age (p = 1.0), male gender (p = 0.08) hyperleukocytosis (p = 0.25) or day 8 blast clearance (p = 0.21). However, T cell phenotype (p < 0.001) was significantly associated with MRD. The 5-year event free survival (EFS) for patients who had MRD versus those who did not was 69% and 61.1% respectively (p = 0.41). The 5-year overall survival (OS) for patients who had MRD versus those who did not was 72.5% and 61.1% respectively (p = 0.33). Flow cytometric techniques can be applied to monitor MRD in patients of ALL undergoing induction therapy. Our results suggest MRD correlates with certain known prognostic factors. Though the EFS and OS was lower in MRD positive patients, the results were not statistically significant probably because of the small sample size.

Primary hepatic marginal zone lymphoma: A rare coincidence.

Primary hepatic lymphoma (PHL) is an extremely rare disease and is often misdiagnosed. The optimal therapy is still unclear and the outcomes are uncertain. Among PHLs, a primary hepatic low-grade marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue is still rarer. The present study reports the case of an elderly female diagnosed with PHL (mucosa-associated lymphoid tissue) and treated with single agent rituximab. After 18 months, she had a progressive disease and developed Waldenstorms macroglobulinemia concomitantly. To date, the patient has received 2 cycles of the RCOP (rituximab, cyclophosphamide, vincristine, and prednisone) regimen and patient's condition is presently stable. This case is reported for its rarity and to convey the importance of the meticulous examination of the tissue. Diagnosis of this condition is important, because the disease is treatable.