Immunity Status of Health Care Workers Post-Recovery from COVID-19: Natural Adaptive Immunity Persists at Nine Months Post-Infection : An Online Longitudinal Panel Survey

Background : Various studies have pinned longevity of protective Immunoglobulin-G (IgG) titres at 2-5 months. The robustness and longevity of the IgG antibody response to COVID-19 infection has been gauged in a cohort of 214 single institutional health care workers by serial quantitative immunometric tests. Currently no separate guidelines exist for vaccination of COVID-survivors and this study provides data to fill this lacuna in knowledge. Methodology : Prospective longitudinal panel survey administered to the same cohort of Health Care Workers (HCW) till such time they got vaccinated under Indian Government’s free vaccination drive for HCW. Depending upon the date of contraction of infection the HCW could be longitudinally monitored for variable periods (2-9 months). The survey questionnaire comprising multiple-choice, dichotomous, matrix and Likert-scale questions was deployed to the respondents online via email/WhatsApp. Data was expressed as box-whisker plots, trendlines and trend areas. A p-value<0.05 was considered statistically significant. The composite index of ‘Effective Immunity’ was calculated. Results : The mean IgG antibody titre was 11.13±8.6AU at 1-2m, 9.68±8.9AU at 3-4m, 8.35±5.9 AU at 6-7m and 7.87±4.4 AU at 8-9m after first symptom, respectively. The lowest titre at all time points was 0 while the highest titres were 46.8 AU, 56.5 AU, 23.4 AU and 17.4 AU at 1-2m, 3-4m, 6-7m and 8-9m, respectively. Conclusion : Adaptive active immunity acquired through natural infection may last for at least 9 months post-initial exposure and lies in the moderate protection range in 77% HCW, which can be extrapolated to vaccination and immunity passports. Separate vaccination guidelines are required for COVID-survivors. The first shot of vaccine serves as a booster second exposure/booster dose in all COVID-survivors.HCW with low IgG-titre may suffer from a false sense of security. Periodic quantitative IgG-titre based serological tests can help guide timing of second shot of vaccination and predict likelihood of re-infection

Histopathological and immunohistochemical clues to the illusive diagnosis of follicular dendritic cell sarcoma: A clinicopathological masquerader

Follicular dendritic cell sarcoma is a rare histiocytic and dendritic neoplasm mainly involving the lymph nodes and selective extranodal sites. They are often misdiagnosed due to nonspecific clinical, radiological, and morphological findings in addition to their rarity. Four cases described below had variable age of presentation, site of involvement, size of the lesion, and histopathological features. Application of an extensive immunohistochemical panel, including a combination of >1 dendritic cell marker, clinched the diagnosis. A combination of D2-40 and Cluster of differentiation 21 (CD21) worked best in establishing a definite role in the current series. Programmed death-ligand 1 (PD-L1) analysis was positive in two of the three cases where it could be performed. However, none of our cases had received immunotherapy. Prompt recognition of the described histopathology features and incorporation of novel immunohistochemical markers can translate to timely initiation of therapy for this aggressive disease

Biomarker testing for advanced lung cancer by next-generation sequencing; a valid method to achieve a comprehensive glimpse at mutational landscape

Background: Next-generation sequencing (NGS) based assay for finding an actionable driver in non-small-cell lung cancer is a less used modality in clinical practice. With a long list of actionable targets, limited tissue, arduous single-gene assays, the alternative of NGS for broad testing in one experiment looks attractive. We report here our experience with NGS for biomarker testing in hundred advanced lung cancer patients. Methods: Predictive biomarker testing was performed using the Ion AmpliSeq™ Cancer Hotspot Panel V2 (30 tumors) and Oncomine™ Solid Tumor DNA and Oncomine™ Solid Tumor Fusion Transcript kit (70 tumors) on IonTorrent sequencing platform. Results: One-seventeen distinct aberrations were detected across 29 genes in eighty-six tumors. The most commonly mutated genes were TP53 (43% cases), EGFR (23% cases) and KRAS (17% cases). Thirty-four patients presented an actionable genetic variant for which targeted therapy is presently available, and fifty-two cases harbored non-actionable variants with the possibility of recruitment in clinical trials. NGS results were validated by individual tests for detecting EGFR mutation, ALK1 rearrangement, ROS1 fusion, and c-MET amplification. Compared to single test, NGS exhibited good agreement for detecting EGFR mutations and ALK1 fusion (sensitivity- 88.89%, specificity- 100%, Kappa-score 0.92 and sensitivity- 80%, specificity- 100%, Kappa-score 0.88; respectively). Further, the response of patients harboring tyrosine kinase inhibitor (TKI) sensitizing EGFR mutations was assessed. The progression-free-survival of EGFR positive patients on TKI therapy, harboring a concomitant mutation in PIK3CAmTOR and/or RAS-RAF-MAPK pathway gene and/or TP53 gene was inferior to those with sole-sensitizing EGFR mutation (2 months vs. 9.5 months, P = 0.015). Conclusions: This is the first study from South Asia looking into the analytical validity of NGS and describing the mutational landscape of lung cancer patients to study the impact of co-mutations on cancer biology and treatment outcome. Our study demonstrates the clinical utility of NGS testing for identifying actionable variants and making treatment decisions in advanced lung cancer

Synergistic Occurrence of EGFR, ALK, and KRAS Gene Mutations in a Patient with Non-small Cell Lung Cancer (Adenocarcinoma)

Lung cancer is a commonly diagnosed malignancy. Adenocarcinoma, a subgroup of non-small cell lung cancer, is the commonest form and presents in an advanced stage of the disease, leaving a limited treatment option. Response to the standard chemotherapy regimens is overall poor. We present a case of synergistic occurrence of triple gene mutations in a patient with well-diff erentiated adenocarcinoma lung treated at a tertiary cancer care center in North India.

Case Report of Non-small Cell Lung Cancer Patient with EGFR T790M Mutation Treated with Th ird Generation Inhibitor

Lung cancer treatment based on the molecular classifi cation of the tumor has paved the way for multiple lines of targeted treatment, even though the development of resistance remains a major cause of concern. Epidermal growth factor receptor (EGFR) remains the poster boy for the use of targeted therapy, and the presence/absence of mutations in this gene has led to the development of inhibitors targeting specifi c mutations. We present the case of an advanced non-small cell lung cancer patient with EGFR T790M mutation treated with Osimertinib, a third-generation inhibitor.

Evaluation of immunohistochemical subtypes in diffuse large B‑cell lymphoma and its impact on survival.

Background and Aim: Diffuse large B‑cell lymphoma (DLBCL) is the most common type of non‑Hodgkin lymphoma in Indian population. The disease could be divided into the prognostically important subtypes, germinal center B‑cell (GCB)‑like and activated B‑cell‑like, using gene expression profiling (GEP). The molecular subtype as defined by GEP could also be predicted by using immunohistochemistry (IHC) based algorithms using three biomarkers CD10, BCL‑6, and multiple myeloma oncogene‑1 (MUM1). It has been confirmed that patients belonging to the GCB subtype have a better outcome and survival than those belonging to the second subtype. The present study was conducted to study the prevalence of these two subgroups and their correlation with survival of the patients. Materials and Methods: A total of 83 patients of DLBCL were included in the study. Hematoxylin‑ and eosin‑stained sections were prepared from the paraffin‑embedded tissue blocks. The staining for all the three antibodies was considered positive when more than 30% cells were stained with the respective antibody. Results: The results showed that 44 patients (53%) had GCB immunophenotype and 39 patients (47%) had non‑GCB phenotype. However, no statistically significant difference in overall and disease‑free survival was noted between the subgroups. Conclusion: This study demonstrated that frequency of GCB subtype of DLBCL is significantly higher than the non‑GCB subtype, and the non‑GCB immunophenotype has better relapse‑free survival 78% (standard error = 0.10) at the end of 3 years, while GCB has 56% (standard error = 0.23). Further studies should be performed with larger number of patients to show difference in clinical outcome between GCB and non‑GCB subgroups.

Simultaneous occurrence of chronic myeloid leukemia and chronic lymphocytic leukemia: Report of an unusual case.

The coexistence of chronic myeloid leukaemia(CML) and chronic lymphocytic leukemia(CLL) has been reported occasionally in literature, with only seven cases of simultaneous occurrence of these two diseases. We present here a case of 57 yr male patient where a complete blood count and differential done using volume conductivity scatter (VCS) technology suggested a diagnosis of CML with CLL. It was further confi rmed by immunophneotyping and cytogenetic analysis. The patient was started on tyrosine kinase inhibitor, 400 mg once daily. Four months after the treatment, patient is doing fi ne with a count of 22 × 109/L and 64% lymphocytes.

Clear cell adenocarcinoma of the male urethral tract.

We present a rare case of clear cell adenocarcinoma of the male bulbomembranous urethra. Mostly these tumors have been described in the female urethral tract with its possible origin from mullerian remnants, wolffian remnants or paraurethral glands. Histologically, these tumors have typically tubulocystic pattern comprising of hobnailed cells with clear glycogenated cytoplasm along with well-defined cytoplasmic membranes. This case is being presented due to its rarity, aggressive behavior and to discuss, trauma as its possible etiological factor

Extrauterine adenomyoma with uterus like features: A rare entity presenting 17 years post hysterectomy.

We report a case of a 47-year-old female (posthysterectomy) with bleeding per vaginam. Imaging studies showed a large abdomino-pelvic mass diagnosed as extrauterine adenomyoma with uterus-like features. This pathological entity is extremely uncommon with only few case reports available in the reported literature. This case is being highlighted for its rarity and to discuss the possible theories for origin of this uncommon condition.

Glomus tumor of the stomach.

Gastric glomus tumors are rare neoplasms. We report here a case of gastric glomus tumor in a 25-year-old female who presented with exsanguinating gastrointestinal hemorrhage. Clinically and on gross examination, the tumor was suspected to be a gastrointestinal stromal tumor (GIST). Histopathological and immunohistochemical evaluation revealed it to be a glomus tumor.

Multiple non-odontogenic cysts--a case report.

Nonodontogenic cysts have been identified at various locations in oral cavity. These occur primarily in relation to fusion of maxillary process either with its counterpart or different portions of nasal part of frontonasal process. Usually solitary, these primarily affect maxilla alone; can rarely be seen in ramus of mandible. We present a case of multiple non-odontogenic cysts involving both maxilla and mandible.

Hypertrophic spinal pachymeningitis presenting as compressive myelopathy: a case report.

Hypertrophic pachymeningitis (HP) is a rare chronic inflammatory process that causes thickening of the dura leading to compressive myelopathy. HP has diverse etiologies like infections, chronic inflammatory processes, collagen vascular diseases and malignancy. We report one such case of HP who presented with compressive myelopathy, underwent decompressive surgery and died due to complications of surgery with the original disease process.

Atypical Whipple's disease.

We report an unusual case of Whipple's disease diagnosed with help from the patient himself. The patient presented with rash resembling dermatitis herpetiformis, constipation, and intermittent diarrhea. A suspicion of celiac disease led to duodenal biopsy, which showed features of Whipple's disease on histology and electron microscopy.

Papillary endothelial hyperplasia in angiokeratoma.

Papillary endothelial hyperplasia (Masson's tumour) is a reactive proliferation of endothelium producing papillary structures with fibrovascular cores. Dilatation, stasis and accompanying inflammation have been incriminated as the inciting events, evident by the presence of this lesion in haemorrhoids, urethral caruncles and laryngeal polyps. We present here a case of papillary endothelial hyperplasia in angiokeratoma hitherto undescribed despite sharing common etiopathogenetic features of dilatation and stasis with other aforementioned lesions.