Study of the association of the known prognostic variables with EGFR expression in head and neck squamous cell carcinomas.

Context: : Head and neck squamous cell carcinomas (HNSCCs) are the sixth most frequent malignancy in the world. Epidermal growth factor receptors (EGFRs) are members of Erb B family of receptors. EGFR is known to act as a driver of tumorigenesis in various carcinomas. Over expression of EGFR in HNSCC is associated with poor prognosis and resistance to radiotherapy. It is a useful prognostic marker, marker for response to therapy, and also a therapeutic target. Aim: To study the association of the known prognostic variables with EGFR expression in HNSCCs and to correlate it with the clinical outcome. Settings and Design: Cross-sectional observational study. Materials and Methods: A total of 170 patients of HNSCC were evaluated for EGFR expression and followed up for at least two years, with correlation of EGFR expression with various histopathological factors and their clinical outcome. Statistical Analysis Used: : Chi-square test. Results: The expression of EGFR in HNSCC in this study population was 88.82%. Statistical significance was noted between EGFR reactivity and age of the patient, its histological grade and perineural invasion. Statistical significance was also noted between EGFR reactivity and recurrence of malignancy as well as the site of recurrence. Conclusion: EGFR expression in patients with HNSCC is a poor prognostic biomarker and has a comparatively lower survival outcome as compared to non-EGFR expressing HNSCC cases. Hence, it will be helpful for all those patients diagnosed with HNSCC to ideally undergo an additional EGFR immunohistochemical evaluation, which, in turn, will help the oncologists in management of the tumor with anti-EGFR therapy combined with radiotherapy, to obtain a better response and a survival outcome.

Phase 1/2 Study of the Timing and Efficacy of 3 mg Peg-GCSF in Neo/Adjuvant Dose Dense Breast Cancer Treatment Protocols.

Amol PatelBackground Peg-GCSF has similar efficacy at a dose of 60 µg/kg and 100 µg/kg. The conventional 6 mg SC dose was based on the maximum tolerable dose. In Japan, 3.6 mg dose was approved on the basis of dose finding studies. Peg-GCSF is an integral part of dose-dense chemotherapy protocols. Dose finding and scheduling study of peg-GCSF have not been conducted in Indian patients. Materials and Methods We conducted two-center phase 1/2 clinical study addressing the timing and efficacy of peg-GCSF in Indian breast cancer patients (CTRI no: 2021/07/034751). Three groups of timing administration were studied, namely 1, 6, and 24 hours post chemotherapy. The phase 2 part was the expansion of the best timing group. The primary objective was dose density, which was defined as receiving chemotherapy on < 3 days of scheduled date. Adriamycin/epirubicin cyclophosphamide (AC/EC) was administered q2 weeks. The total leucocyte (TLC) and absolute neutrophil (ANC) kinetics were studied. Other outcomes were incidence of grade 4 neutropenia, febrile neutropenia (FN), and requirement of additional doses of G-CSF. Bone pain, fever, and myalgia were studied for adverse effects. Results From November 20 to December 21, 36 patients were enrolled. Patient characteristics are depicted in Table 1. Initially, three patients received the peg-GCSF in each timing group. One patient in each 1-hour and 6 hours needed G-CSF support for maintaining the dose density. The 24-hour group was carried to phase 2 part. Dose density was maintained in 97% of patients. None of the patient in 24-hour group had FN. Also, 4/30 patients had grade 4 neutropenia and required an additional dose of GCSF. Grade 3 or 4 bone pain was not noticed by any of the patients. During the first cycle, the mean ANC (cells/µL) was 5284, 20704, 3010, 6954 on D0, D + 3, D + 7, and D + 13, respectively (Fig. 1A-TLC and 1B-ANC). The mean ANC (cells/µL) rise on D + 3 in cycles 1, 2, 3, 4 was 23810, 29209, 32428,22455, respectively. Conclusion Dose density of AC/EC breast cancer protocol is maintained with peg-GCSF 3 mg. Post chemotherapy 24-hour timing of peg-GCSF administration remains as the standard. A phase 3 trial of 6 mg versus 3 mg is warranted.

68 Ga-PSMA-11 PET/CT Imaging in Brain Gliomas and Its Correlation With Clinicopathological Prognostic Parameters.

BACKGROUND: Gliomas are the most common primary central nervous system tumors, of which the malignant gliomas account for 60%-75%. The primary and secondary brain malignancies are highly treatment resistant, and their marked angiogenesis attracts interest as a potential therapeutic target. The grade of gliomas, Ki-67 index, and IDH mutation status are among the major prognostic markers in gliomas. Prostate-specific membrane antigen (PSMA) is a zinc-dependent peptidase that is not only expressed in prostate cancer cells but also in the tumor neovasculature. The initial PSMA PET studies in central nervous system tumors using 68 Ga-HBED-CC-PSMA ( 68 Ga-PSMA-11) PET tracer confirmed selective target expression in gliomas of different grades, with higher expression in high-grade glioma compared with low-grade glioma. AIMS AND OBJECTIVES: The aim of the present study was to correlate and compare the 68 Ga-PSMA-11 and 18 F-FDG uptake in brain tumors with their clinicopathological prognostic parameters, so as to study their prognostic implications. In addition, the study also aimed to identify patients who are likely to benefit from potential PSMA-targeted therapies. PATIENTS AND METHODS: This ongoing prospective study was approved by the institutional scientific and medical ethics committee. The patients with primary or recurrent glioma lesions on MRI underwent regional brain PET/CT scanning with 68 Ga-PSMA-11 and 18 F-FDG. The final histopathology of the brain lesions (glioma grade), Ki-67 index, and IDH mutation status were compared with SUV max values of the 68 Ga-PSMA-11 and 18 F-FDG PET/CT. RESULTS: A total of 15 patients (13 males and 2 females; age range, 21-73 years; median age, 58 years) were included in this study analysis. Among the 15 patients, 10 were treatment naive and 2 were patients with recurrent glioma. Three patients turned out to be WHO grade I-II, 6 belonged to grade III, and 6 grade IV (glioblastoma multiforme) on final histopathology. The 68 Ga-PSMA-11 PET/CT showed tracer uptake in all high-grade gliomas with good tumor-to-background ratio. It was PSMA nonavid in 2/3 low-grade gliomas, and it showed low-grade uptake in 1/3 patients. PSMA expression (as evaluated by SUV max values) was significantly higher in higher-grade tumors, those with IDH mutation wildtype status, and higher Ki-67 indices. FDG PET SUV max also showed significant correlation with these prognostic parameters. CONCLUSIONS: In these preliminary results, PSMA PET appears to be an important tool in the evaluation and prognosis of gliomas. PSMA-directed theranostics can be explored as a personalized approach in gliomas with high PSMA uptake. However, with the limitation of small sample size, larger clinical trials are warranted to draw conclusive evidence regarding the same.

A pilot study on DNA hypermethylation status in promoter region of P16 gene in patients with sporadic breast cancer.

Background: Epigenetic modification of cancer-related genes plays a role over and above their genetic alterations and contributes to the tumor initiation and progression of breast cancer. Promoter methylation of tumor suppressor genes is one such epigenetic modification, which can be potential biomarker. In this study, promoter methylation status of p16 gene was studied in blood samples of patients with breast carcinoma. Methods: Seventy-five patients, freshly diagnosed with carcinoma of breast and 20 age and sex matched healthy control subjects were recruited for the study. DNA extracted from EDTA blood sample was bisulfite converted and subjected to methylation-specific PCR to amplify the p16 promoter region. Results: Out of 75 patients, 25 (33%) patients showed hypermethylation in promoter region of p16 gene, which was statistically significant in comparison with the control group (p < 0.05). In subgroup analysis, lymph node involvement, cancer grade, and histopathological finding did not show any difference with methylation status of p16 promoter. Conclusion: Significant hypermethylation of p16 promoter region in the blood of histopathologically proven cases of breast cancer was observed suggesting promoter hypermethylation of p16 may be a possible mechanism accounting for sporadic carcinoma of breast.

Clinico-etiological characteristics of organizing pneumonia: A retrospective study.

INTRODUCTION: Organizing pneumonia (OP) is an idiopathic interstitial pneumonia characterized radiologically by the patchy peripheral areas of ground-glass opacities and consolidation. It is commonly associated with a variety of conditions such as connective tissue diseases (CTD), drugs, infections, malignancy, radiation exposure, post-transplant, and other interstitial pneumonia. There are no specific clinical manifestations unless there is an underlying etiology. We present a series of such cases. AIMS AND OBJECTIVES: The aim of the study was to identify the clinical characteristics and etiological spectrum of patients manifesting radiologically with OP pattern. MATERIALS AND METHODS: This was a retrospective analysis of clinico-radiological profile and etiological diagnosis of 23 patients, who had a radiological diagnosis of OP during the period of January 2017-September 2019. RESULTS: Our patients presented with nonspecific symptoms of cough, fever, breathlessness, and occasionally with hemoptysis. The various etiologies identified were CTD (n = 4), infection (n = 2), drugs (n = 4), radiation (n = 1), chronic aspiration syndrome (n = 1), malignancy (n = 2), hypersensitivity pneumonitis (n = 1), and chronic heart failure (n = 2), and in majority (n = 7), no underlying etiology was evident and were labeled as cryptogenic organizing pneumonia. CONCLUSION: OP is an underdiagnosed entity and is associated with numerous diseases varying from pulmonary tuberculosis to malignancy. Identification of the underlying disease process is of paramount importance as it enables the treating physician to implement necessary therapeutic interventions.

Primary Breast Tumors with Mesenchymal Morphology.

Overview Mesenchymal tumors of the breast are rare. Few epithelial tumors also have mesenchymal components. It is crucial to identify these as per histogenesis. This can be facilitated by markers of epithelial-mesenchymal transition (EMT). Objectives The aim of this study was to categorize the breast lesions with mesenchymal morphology and to study EMT on immunohistochemistry (IHC). Materials and Methods This is a retrospective study of 5-year duration from January 2015 to December 2019. Inclusion criteria: all breast lesions showing mesenchymal/nonepithelial morphology, complete or partial, on histology. Exclusion criteria: Mammary carcinomas without any mesenchymal/nonepithelial morphology, fibroadenomas, and lymphomas. Demographics, clinical, gross examination, histology, and IHC findings of selected cases were reviewed and recorded. Three additional markers p53, E-cadherin, and ß-catenin were performed. Statistical Analysis Used Frequency calculation for each variable (IHC). Results Thirteen (2.5%) out of total 510 breast specimens showed mesenchymal histology. Of these, five (38.5%) were metaplastic breast carcinomas (MBC), four (31%) were phyllodes tumor (PT), and one (7.7%) case each of malignant peripheral nerve sheath tumor, primary stromal sarcoma of breast, pseudoangiomatous stromal hyperplasia, and myofibroblastoma. Loss of E-cadherin was seen in 4/5 (80%) MBCs and was retained in ductal component of PTs. p53 was not expressed in any of the tumors except 3/5 (60%) MBCs. ß-Catenin was aberrant in all MBCs. Conclusions Primary breast tumors with mesenchymal morphology present a spectrum ranging from benign mesenchymal, fibroepithelial neoplasms to malignant tumors of mesenchymal and epithelial origin. Loss of E-cadherin, expression of p53, and aberrant expression of ß-catenin are suggestive of EMT and molecular heterogeneity of MBCs.

Isolated saccular aneurysm of the external jugular vein

Venous aneurysm of the head and neck is a rare clinical entity due to its asymptomatic nature and tendency of clinicians to report only surgical results. Whereas the primary aneurysm of internal jugular vein (IJV) in children is being increasingly recognized, secondary aneurysms of veins of the head and neck in adults, notably the external jugular vein (EJV) aneurysm remains only in anecdotal case reports. We present the case of a 63-year-old previously healthy woman who presented with a gradually progressive right lateral neck swelling over the last 18 months. Following the evaluation, she was diagnosed as a case of isolated spontaneous right-sided EJV aneurysm and was managed by surgical excision of the aneurysm.

A Rare Case of Poikilodermatous Mycosis Fungoides.

Poikilodermatous mycosis fungoides (PMF) is a rare clinical variant of early-stage mycosis fungoides with peculiar histological features and with low risk of disease progression. Since poikiloderma can coexist with classical mycosis fungoides lesions, PMF can only be considered when poikilodermatous lesions are predominant (>50% of lesions). We here report one such rare case of PMF with poikilodermatous lesions covering almost 70% of the body surface and with characteristic clinical, histopathological, dermoscopic, and immunohistochemical findings.

A Rare Presentation of Concurrent Onset and Coexistence of Generalized Lichen Planus and Psoriasis in a Child.

Independently, psoriasis and lichen planus (LP) are common inflammatory skin conditions affecting around 2-3% and 1% of the population, respectively. However, the coexistence of both diseases is rare. Common immunological mechanisms with altered T-cell-mediated autoimmunity, cytokine milieu, and Koebner phenomenon play a role in their pathogenesis. As reviewed in the literature, psoriasis may independently be associated with other autoimmune conditions like vitiligo, alopecia areata, LP, and discoid lupus erythematosus. A rare co-occurrence of these two or three autoimmune diseases has been reported. Here, we report a case of a 10-year-old boy who presented with persistent nonpruritic multiple hyperpigmented scaly papules and plaques over the body since 6 months of age. Histopathology revealed features suggestive of both LP and psoriasis in the same section. A diagnosis of psoriasis-LP overlap was made, and the patient was managed with tab acitretin 25 mg daily and narrowband ultraviolet B (NBUVB) phototherapy with which he showed satisfactory clearance of the lesions.

Isolated saccular aneurysm of the external jugular vein.

Venous aneurysm of the head and neck is a rare clinical entity due to its asymptomatic nature and tendency of clinicians to report only surgical results. Whereas the primary aneurysm of internal jugular vein (IJV) in children is being increasingly recognized, secondary aneurysms of veins of the head and neck in adults, notably the external jugular vein (EJV) aneurysm remains only in anecdotal case reports. We present the case of a 63-year-old previously healthy woman who presented with a gradually progressive right lateral neck swelling over the last 18 months. Following the evaluation, she was diagnosed as a case of isolated spontaneous right-sided EJV aneurysm and was managed by surgical excision of the aneurysm.

Application of International association for the study of lung cancer/American Thoracic Society/European Respiratory Society criteria for the diagnosis of lung carcinomas on small biopsies: A tertiary care center experience.

BACKGROUND: The new IASLC/ATS/ERS classification provides standardized terminology for lung cancer diagnosis in small biopsies and cytology specimens. OBJECTIVES: The aim was to study the feasibility of the guidelines using one marker for adenocarcinoma (ADC) and one for squamous cell carcinoma (SQCC) in non-small cell lung carcinomas (NSCLCs). SUBJECT AND METHODS: In this study, we reviewed all the formalin-fixed paraffin-embedded tissue blocks diagnosed as lung carcinoma between July 2016 and December 2017. Cases were labeled as SCLC, ADC, SQCC, NSCLC favor ADC, NSCLC favor SQCC, NSCLC-not otherwise specified (NOS), and NSCLC-NOS possible adeno-SQCC (ADSQCC) as per IASLC/ATS/ERS 2011 guidelines. A three-step approach incorporating morphology, immunohistochemistry (IHC), and molecular analysis was used. RESULTS: One hundred and nine cases were included. Six of the 109 cases were SCLC and 1 case was of large-cell neuroendocrine type. Of the remaining 102, 51 were diagnosed based on their classical histomorphology into SQCC (8) and ADC (43). Remaining 51 cases required IHC/special stains for categorization. The panel comprised anti-CK7, anti-thyroid transcription factor-1 (TTF-1), and anti-p63. Twenty-nine were positive for anti-TTF-1 and thus labeled as NSCLC favor ADC. Fifteen were labeled as NSCLC favor SQCC as they were highlighted by anti-p63. Four cases showed reaction to both the antibodies in different sets of tumor cells and thus were classified as NSCLC-NOS, possible ADSQCC. Remaining 3 cases did not show reaction to any of the antibodies and hence were labeled NSCLC-NOS. CONCLUSION: The need for every laboratory to use minimal tissue for ancillary tests to diagnose lung carcinoma on small biopsies is reemphasized. Tissue from small biopsies needs to be preserved not only for the diagnosis but also for molecular testing and evaluation of markers of resistance to therapy, in this era of personalized medicine.

Osteoclastic variant of anaplastic thyroid carcinoma: A case report of rare entity.

Anaplastic thyroid carcinoma (ATC) is a rare, highly malignant thyroid tumor with dismal prognosis. Osteoclastic giant cell variant of ATC is extremely rare and is characterized by the presence of a large number of multinucleated giant cells resembling osteoclasts. We report here this unusual variant in a 67-year-old female with a history of long-standing goiter of 13 years duration. Histologically, many multinucleated osteoclast-like giant cells were seen accompanying the malignant spindle cell component. Despite extensive sampling, no evidence of differentiated thyroid malignancy could be elucidated.

A dissimulate presentation of histoid Hansen's disease in the form of erythema nodosum leprosum.

Hansen's disease is a chronic infectious granulomatous disease with varied clinical presentation. Histoid Hansen's disease is an important emerging lepromatous subset of Hansen's disease known to mimic varied dermatoses. Occurrence of reactions, especially erythema nodosum leprosum (ENL), is rare in this form of leprosy. We report a case of Histoid Hansen's disease with initial presentation of ENL while undergoing management for infertility.

Two atypical presentations of lepra reactions.

Leprosy or Hansen's disease is a chronic infectious granulomatous disease with varied presentation, especially in the setting of lepra reactions. We report two such atypical presentations each of Type I and Type II Lepra reactions; the first being an elderly male presenting with fever, while the second case being of a young boy being evaluated for cervical lymphadenitis.

Invasive cutaneous mucormycosis in a preterm neonate presenting as a vesicobullous lesion.

Mucormycosis is a relatively rare fungal infection seen in immunocompromised patients. Very few cases of invasive cutaneous mucormycosis occurring in neonates have been reported in literature. It is an aggressive disease with a mortality rate of around 64% in neonates, so a high index of suspicion is essential for rapid diagnosis and definitive treatment with broad-spectrum antifungals such as Amphotericin B. We present a case of a premature infant born at 25 weeks of gestation who developed vesicobullous lesions all over the body on day 5 of life. Biopsy from the vesicles confirmed the presence of angioinvasive fungal hyphae of mucormycosis which were highlighted on Periodic acid-Schiff and Grocott stain.

Primary Cutaneous B-cell Lymphomas: Case Report of Two Cases.

Primary cutaneous lymphomas are a unique, heterogeneous group of lymphoproliferative disorders which have a primary cutaneous manifestation in the absence of systemic involvement of lymph nodes, bone marrow, or visceral organs at the time of diagnosis. Among the primary cutaneous lymphomas, B-cell lymphoma is much less common and accounts for 20%-25% of cases. Primary cutaneous diffuse large B-cell lymphomas (PCDLBCLs) are aggressive neoplasms with poor prognosis. Early and accurate diagnosis is required as these patients respond well to systemic anthracycline-based chemotherapy (R-CHOP). In this article, we report two cases of PCDLBCL, other which presented with rapidly enlarging skin nodules and were diagnosed based on clinical features, histomorphology, and characteristic immunohistochemical expression. Both the patients were treated with systemic chemotherapy and responded well. During the 6 months' follow-up period, the lesions regressed. The patients are symptom free with no evidence of disease relapse or dissemination to extracutaneous sites.

Autopsy findings of miliary tuberculosis in a renal transplant recipient.

Miliary tuberculosis is a lethal form of disseminated tuberculosis (TB), deriving its name from the millet-seed-sized granulomas in multiple organs. As TB still remains a leading cause of morbidity and mortality in India, its disseminated forms need to be diagnosed early to ensure more aggressive treatment at the earliest possible time. However, a considerable number of cases are missed ante-mortem. We discuss the case of a 32-year-old immunocompromised, non-HIV patient with an ante-mortem diagnosis of pulmonary TB. However, multiple organ involvement by Mycobacterium tuberculosis was demonstrated on autopsy. This case highlights the role of autopsy as a research and learning tool, and prudential clinico-pathologic correlation, which will improve clinical outcomes in the future.