Long-term clinical outcomes of male breast cancer patients treated with curative intent by trimodality therapy at an academic university hospital in India.

INTRODUCTION: Male breast cancer is rare and accounts for less than 1% of all breast cancer cases worldwide. METHODS: This retrospective cohort study included all patients of invasive male breast cancer treated with curative intent by a trimodality approach via a multidisciplinary team at an academic university hospital in India between 2009 and 2023. Records were identified from a prospectively maintained database. Clinicopathological parameters, treatment details and survival were recorded and analysed. RESULTS: Thirty-four patients were included. The median (IQR) age was 55(44-63) years. Most patients were overall stage III (74%) and node positive (79%) with Scarff-Bloom-Richardson grade II (50%). Twenty-five patients (73%) were oestrogen receptor (ER) positive. Lymphovascular space invasion (LVSI) and perineural invasion (PNI) were present in 62% and 21% of patients, respectively. The most common chemotherapy timing was adjuvant (53%) followed by neoadjuvant (41%), and the most commonly used regimen consisted of a combination of doxorubicin-cyclophosphamide followed by a taxane (53%). Most (85%) patients underwent a mastectomy, five patients underwent breast conservation. All patients received radiotherapy to a dose of 42.6 Gy in 16 fractions, followed by a tumour bed boost for those undergoing breast conservation. At a median follow-up of 70 months (range 10-159 months), the five and ten-year overall survival was 91% and 58%, and the five-year disease-free survival (DFS) was 67%. The median DFS was 72 months. On univariate analysis, the tumour sub-type (Luminal versus TNBC) significantly predicted DFS (P = 0.03 log-rank). CONCLUSION: Breast cancer in males has a high incidence of node positivity, ER positivity and LVSI. Even with advanced stages at presentation, trimodality therapy in a multidisciplinary setting offers good long-term outcomes.

Cancer stem cell biomarkers SOX2 and Oct4 in cervical cancer patients undergoing chemoradiotherapy.

BACKGROUND: Cancer stem cell biomarkers SRY (sex-determining region Y)-box 2 (SOX2) and octamer-binding transcription factor 4 (Oct4) account for radioresistance in cervical squamous cell cancers (CSCCs). Their clinical implications are limited and contradictory. METHODS: In this prospective cohort study, we recruited patients with FIGO IB2-IVA CSCC treated with primary chemoradiotherapy on regular follow-up. Tissue biopsy specimens were evaluated for SOX2 and Oct4 expression by immunohistochemistry, quantified by a product of proportion and intensity scores. RESULTS: A total of 59 patients were included. Most had a moderately differentiated (81%), keratinizing (59%) CSCC, and ≥FIGO stage IIB disease (95%). SOX2 expression (high:low 21:38 patients) and Oct4 expression (high:low 4:55 patients) had a significant interrelation (p = 0.005, odds ratio (95% CI) - 1.23 (1.004-1.520)). At a median follow-up of 36 months, the 3-year overall survival (OS) was 60% and 53% for low and high SOX2 expression (p = 0.856), and 54% and 100% for low and high Oct4 expression (p = 0.114). The 3-year disease-frese survival (DFS) was 65% and 50% in the low and high SOX2 expression (p = 0.259), and 59% and 75% for low and high Oct4 expression (p = 0.598). SOX2 expression was the only variable significantly associated with a lower OS and DFS on regression analysis. CONCLUSION: Our study demonstrated a trend toward improved OS and DFS with low SOX2 and high Oct4 expression in CSCC patients undergoing chemoradiotherapy.

Evaluation of HER2Neu Status in Periampullary Cancers in Tertiary Care Centre in Northern India: A Three-Year Retrospective Study.

Background Periampullary carcinoma is a heterogeneous group of malignancies, and despite advances in treatment, its mortality rate remains high. A better understanding of the disease and factors influencing its course and potential therapeutic targets is imperative for improving its overall outcome. Through comprehensive cytogenetic analysis, it has been established that the development of periampullary carcinogenesis involves specific chromosomal aberrations, dysregulation of oncogenes, and suppression of genes in a multistep progressive manner. Our study aimed to evaluate the expression of human epidermal growth factor (HER2Neu) in periampullary cancers using immunohistochemistry and fluorescent in situ hybridization. Material and methods This was a retrospective study in which all consecutive cases of periampullary carcinoma diagnosed over a period of three years were evaluated. HER2neu expression was analyzed using immunohistochemistry (IHC) and fluorescent in-situ hybridization (FISH). Histopathological evaluation was performed according to the College of American Pathologists (CAP) protocol. Results Twenty patients were diagnosed during the study period. On histomorphologic analysis, most cases (n=17) were diagnosed as well-differentiated adenocarcinomas, the most common subsite being the ampulla of Vater and pathological staging as pT2N0Mx. On IHC, no overexpression of HER2Neu was reported in any case, but FISH analysis revealed one point of amplification with HER/centromere enumerator probe (CEP) ratio>2. Conclusion HER2Neu evaluation in periampullary carcinoma has limited value; thus, it could have a restricted therapeutic role.

Expression of immune checkpoint protein in oral squamous cell carcinoma and its clinicopathological correlation: A tertiary care center cross-sectional study.

Background: Recent evidence suggests that oral squamous cell carcinoma (OSCC) patients who exhibit the immunohistochemical expression of immune checkpoint protein programmed cell death ligand 1 (PD-L1) are more likely to have a poor clinical outcome and may serve as an independent prognostic marker. Aims and Objectives: This study aimed to assess the immunohistochemical expression of immune checkpoint protein PD-L1 in OSCC and its clinicopathological correlation. Materials and Methods: OSCC cases were included in the study. This was a tertiary care center cross-sectional one-year duration study. Histomorphological diagnosis and immunohistochemical expression of PD-L1 were performed after taking ethical clearance. The statistical analysis was performed using Statistical Package for Social Sciences (SPSS) version 21.0 statistical analysis software. Results: A total of 106 cases of OSCC were included in the study. Histologically, the majority of cases (58.5%) were graded as well differentiated, followed by moderately differentiated (58.5%) and poorly differentiated (4.7%), respectively. In PD-L1 immunohistochemical expression, score 1+ was accorded to 37 (34.9%), 2+ was accorded to 31 (29.2%), and score 3+ was accorded to 33 (31.1%) cases. Tumor size, pattern, depth of invasion lymphovascular invasion (LVI), and perineural invasion (PNI) were found to be significantly associated with PD-L1 immunohistochemical scores. Conclusions: We concluded that the immunohistochemical expression of immune checkpoint protein PD-L1 positivity in tumor cells was seen in the majority of the cases (60.37%) in our patient. This suggests that the PD-1 or PD-L1 pathway plays a significant role in tumor immune evasion in OSCC.

Immunohistochemical Expression of p16 and CDK4 in Soft Tissue Tumors.

BACKGROUND AND OBJECTIVES:  The aim of this study was to determine the immunohistochemical expression of p16 (p16INK4a) and cyclin-dependent kinase 4 (CDK4) and CDK4 markers in various lineages of soft tissue tumors and to evaluate their role in differentiating atypical lipomatous tumors/well-differentiated liposarcomas from benign lipomas. MATERIAL AND METHODS: A total of 70 cases of both excisional and incisional biopsies of soft tissue tumors were included in this study. Histopathological examination was done by using formalin-fixed, paraffin-embedded tissue samples. After that, we performed IHC expressions of p16 and CDK4 markers on the unstained slides of these soft tissue tumors.  Results: Immunohistochemical study showed that positive expressions of p16, CDK4, and combined (p16+CDK4) markers were 51.4%, 10.0%, and 12.9%, respectively in soft tissue tumors. Positive p16 expression was observed among a higher proportion of malignant cases (66.7%) as compared to benign (20.0%) and intermediate (50.0%) cases. This difference was found to be statistically significant (p=0.009). Negative expression of only CDK4 and combined (p16 and CDK4) were observed among a higher proportion of benign as compared to malignant and intermediate cases (90.0% vs. 78.6% & 75.0%, p=0.393 and 65.0% vs. 26.2% & 37.5%, p=0.028, respectively). This difference was not found to be statistically significant. For adipocytic tumors, the majority of malignant and intermediate tumors had positive p16 (7/7; 100%) and CDK4 (6/7; 85.7%) immunohistochemical expression. These differences were found to be statistically significant. CONCLUSION: Immunohistochemical marker p16 can be used to differentiate between malignant and benign soft tissue tumors. Amongst adipocytic tumors, combination of p16 and CDK4 immunohistochemical expression can be used to differentiate liposarcomas from benign ones.

Immunohistochemical appraisal of epithelial mesenchymal transition type III in gall bladder cancer.

Background: Epithelial-mesenchymal transition (EMT) is the heart of invasion. EMT associated with cancer progression and metastasis is known as type III EMT. Beta-catenin, E-cadherin, and MMP9 markers of EMT are routinely employed for diagnostic purposes. Aims: We employed these markers to study EMT by immunohistochemistry (IHC) in gall bladder cancer (GBC) with respect to depth of tumor invasion, clinical outcome, and disease-free survival. Settings and Design: This was a prospective case-control study. Material and Methods: Seventy gall bladders were included (50 GBC and 20 CC). After detailed histology, immunoexpression was studied in terms of percentage and strength of expression. Statistics Analysis Used: Expression was compared between CC and GBC by Student t test and analysis of variance. Kaplan-Meier was used for survival analysis, and the extent of agreement ("Kappa") was calculated. Results and Conclusions: The age of incidence of GBC was 49.40 (+11.6) years with female predominance (F:M = 4:1). In 88% (44/50) of GBC, the fundus was involved. Moderately differentiated adenocarcinoma was most frequent [54%; 27/50]. Significant downregulation of E-cadherin (P = 0.022) and beta-catenin (P < 0.001) and upregulation in MMP9 (P < 0.001) were seen in GBC with respect to CC with significant association among them. MMP9 expression was significantly associated with higher tumor stage but with chemotherapeutic response. Our results display that epithelial-mesenchymal transition type III plays a role in GBC invasion. MMP9 overexpression and loss of membranous beta-catenin may be considered a marker for poor clinical outcomes and advanced disease.

Primary Pure Intrarenal Yolk Sac Tumor in 1.5-Year-Old Boy-A Rare Case Report.

Germ cell tumors primarily arise in gonads and extragonadal germ cell tumors, an uncommon entity, originates usually along the midline. Here, we report the fifth example of intrarenal pure yolk sac tumor in a 1.5-year-old boy who presented with abdominal pain and underwent excision of the mass for suspected Wilms tumor. On histopathology and immunohistochemistry, a diagnosis of a yolk sac tumor was rendered. Postoperative serum alpha-fetoprotein levels were 21 000 ng/dl. The purpose of this report is to emphasize the importance of suspecting a germ cell tumor as one of the differential diagnoses of a suspected case of Wilms tumor and the significance of evaluating serum alpha-fetoprotein levels preoperatively.

Detection of Epstein Barr Nuclear Antigen-1 (EBNA-1), Early Antigen 1F, 2R (EA-1F, EA- 2R) along with Epstein-Barr virus Latent Membrane Protein 1 (LMP1) in Breast Cancer of Northern India: An Interim Analysis.

INTRODUCTION: Worldwide, breast cancer (BC)  is a prominent cause of death, with a disproportionately high incidence in developed countries. Epstein-Barr virus (EBV) infection has been reported in up to 90% of the world's population.  Although the exact link of EBV infection and breast carcinoma is not yet determined. The present study was carried out to assess the pathological correlation of EBV infection and BC in women from Northern India. METHODOLOGY: In this prospective observational study, 130 patients with histologically proven breast carcinoma were included. After detailed histology, the paraffin block with infiltrative tumor was selected for molecular analysis and further immunohistochemistry (IHC)- EBV PCR and Epstein-Barr virus latent membrane protein 1 (LMP1) IHC. RESULTS: Most of the patients were diagnosed with Infiltrating Ductal Carcinoma not otherwise specified (IDC-NOS), followed by Infiltrating Ductal Carcinoma + Ductal Carcinoma in situ (IDC + DCIS). The total of 25 tissues of breast carcinoma had positive EBV PCR results (19.23%). The co-relation between the molecular and immunohistochemical results was significant in 11/25 cases that showed immunoexpression for LMP1 by IHC. Sensitivity of 44% and specificity of 100% were observed for LMP1 IHC, having a PPV value of 100% and an NPV of 88%. No significant correlation was observed between age, tumor subtype, grade, stage with respect to EBV infection; however, there was a significant association with nodal metastasis with extra nodal extension in tumors that had EBV infection. CONCLUSION: The present study establishes an association between LMP1 and patients with EBV positive breast cancer. The authors suggest that additional multicentric studies be conducted to strengthen the reliability and generalizability of the observations of the current study.

Can dual staining with p16 and Ki67 be biomarkers of epithelial dysplasia in oral lesions?

Background: Oral carcinogenesis is a multistage process with epithelial dysplasia as a premalignant condition. There is a significant inter-observer variation in diagnosing and grading the oral epithelial dysplasia. As human papillomavirus (HPV) is believed to have à strong relationship with oral carcinogenesis, using P16 as a biomarker may help in identifying the cells which may be undergoing the malignant transformation. However, due to the low specificity of P16, dual staining test P16INK4/Ki67 might be a better promising marker for identifying the transformed cells. This study was designed to evaluate the dual expression of P16 and Ki67 as a promising biomarker for dysplasia and their correlation with clinicopathological factors. Materials and Methods: Immunohistochemical analysis for p16 and ki67 was performed on 30 premalignant oral lesions and 36 oral squamous cell carcinoma (OSCC) by dual staining using the CINtec PLUS kit. Results: CINtec positivity was observed only in leukoplakia with dysplasia (46.7%) and squamous cell carcinoma (25%). None of the cases of leukoplakia without dysplasia or oral submucosal fibrosis stained positive for CINtec plus staining. In leukoplakia with dysplasia, there was no significant association with any of the clinicopathological parameters studied. In OSCC cases, alcohol intake showed statistically significant association with CINtec positivity. Conclusion: P16INK4/Ki67 assessment by dual staining is a promising biomarker for identifying dysplasia in cases with diagnostic dilemmas.

Melanotic neuroectodermal tumor of infancy (MNTI) - A rare entity.

Melanotic neuroectodermal tumor of infancy is a rare pigmented pediatric tumor seen at craniofacial sites with the most common site being maxilla. This tumor arises from neural crest origin with a polyphenotypic expression of epithelial, neuroblastic, and melanotic markers. It is a locally aggressive tumor with rapid, expansile, and destructive growth. The tumor has fairly high chances of recurrence and malignant transformation, if not diagnosed and treated with time. There is no standard protocol for management owing to its rarity. Hereby, we present one such case of a 2-month-old male child with rapidly enlarging upper jaw swelling. The patient was treated with wide local excision, followed by two cycles of chemotherapy. The patient is in follow-up and doing well with no evidence of any local recurrence or metastasis till date.

Rare presentation of cervical deciduosis as antepartum haemorrhage.

Cervical deciduosis refers to the condition in which ectopic decidual changes take place in the cervix. It is mostly asymptomatic but sometimes may have various clinical presentations. In our case, patient had a rare clinical presentation of cervical deciduosis, in the form of an antepartum haemorrhage at 32 weeks. On examination, there were multiple friable lesions measuring 5-15 mm in size on both the lips of the cervix and it was very much simulating to malignancy, so biopsy was done. However, biopsy led to uncontrolled bleeding and finally the patient required premature lower segment caesarean section. Both mother and baby were well. Biopsy report was diagnostic of cervical deciduosis. On follow-up at 6 weeks post partum, the cervix was found to be absolutely healthy. Since, cervical deciduosis is a benign condition which gets resolved 4-6 weeks post partum. So, keeping differential diagnosis of cervical deciduosis in mind is very important to avoid unnecessary cervical biopsies during pregnancy. And patient with suspicion of cervical deciduosis should be followed up postpartum strictly.

Polymorphous adenocarcinoma of the submandibular gland.

Polymorphous adenocarcinoma (PA) of the salivary glands is a rare malignancy that predominantly affects the minor salivary glands of the palate. Major salivary gland involvement is rare (<5%). The submandibular gland is a highly unusual location for this tumour. Recently, the WHO has updated the classification of salivary gland tumours in which the PA subtype has been modified. We report a very uncommon case of a classical variant of PA involving the submandibular gland in a 49-year-old woman managed at our institute and discuss the most recent pathological criteria for diagnosis, management strategy and prognosis of PA.

A rare case report of transitional urothelial carcinoma metastasizing to isolated upper cervical lymph node diagnosed on cytology.

Transitional urothelial carcinoma frequently metastasizes to pelvic and retroperitoneal lymph nodes usually within 2 years of primary diagnosis but isolated metastasis to upper cervical lymph node after 5 years of primary diagnosis is extremely rare. We report here a case of a 53-year-old male who presented with Level II cervical node enlargement after 5 years of being diagnosed and treated for urothelial carcinoma. The diagnosis of cervical metastasis from urothelial carcinoma was suggested by fine-needle aspiration cytology and confirmed by immunocytochemistry.

Surgical outcomes in oral cancer involving the central arch of the mandible in elderly patients: An institutional experience.

BACKGROUNDS: Oral squamous cell cancer (SCC) is one of the most common cancers. The most common age of presentation is fifth to sixth decade. Management of this disease is dictated by stage, age, and related comorbidities. Elderly patients have their own set of limitations as far as their management is concerned. Carcinoma involving central mandibular arch is a challenging disease for surgeons, especially in the elderly. This article describes our experience with the surgical treatment of oral cancer involving the central arch of the mandible in elderly patients. METHODS: Forty elderly (≥60 years) patients with histologically proven SCC of the oral cavity in which disease was involving the central arch of the mandible, were included in our study. Demographic, clinical, and treatment-related factors were recorded. The outcome was assessed in terms of postoperative complications, recurrence, and patient survival. RESULTS: The median age of the patients was 63 years. The male:female ratio was 7:3. A history of oral tobacco use was present in 95% of patients. The most common site of disease was lower alveolus (80%) followed by carcinoma of the lower lip (20%). Majority of our patients (77.3% [30]) were having Stage IV disease. Mandibulectomy was either segmental (62.5%) or marginal (37.5%). Bilateral neck dissection (37/40, 92.5%) was done in most patients. Among all patients, 62.5% (25) received adjuvant radiotherapy. The local recurrence rate after a median follow-up of 30 months was 15% (6). Two-year disease-free survival and overall survival were 89% and 90%, respectively. CONCLUSION: Central arch of the mandible is a difficult disease to treat. It needs a complex and lengthy reconstructive procedure. Comorbidities such as extreme age, diabetes, and pulmonary and cardiac illnesses make it more challenging to manage. With the proper evaluation of comorbidities and avoiding long, cumbersome procedures, we can provide patients a fairly good chance of survival.

Continuing cancer surgery through the first six months of the COVID-19 pandemic at an academic university hospital in India: A lower-middle-income country experience.

BACKGROUND: The novel coronavirus pandemic (COVID-19) hinders the treatment of non-COVID illnesses like cancer, which may be pronounced in lower-middle-income countries. METHODS: This retrospective cohort study audited the performance of a tertiary care surgical oncology department at an academic hospital in India during the first six months of the pandemic. Difficulties faced by patients, COVID-19-related incidents (preventable cases of hospital transmission), and modifications in practice were recorded. RESULTS: From April to September 2020, outpatient consultations, inpatient admissions, and chemotherapy unit functioning reduced by 62%, 58%, and 56%, respectively, compared to the same period the previous year. Major surgeries dropped by 31% with a decrease across all sites, but an increase in head and neck cancers (p = .012, absolute difference 8%, 95% confidence interval [CI]: 1.75% - 14.12%). Postoperative complications were similar (p = .593, 95% CI: -2.61% - 4.87%). Inability to keep a surgical appointment was primarily due to apprehension of infection (52%) or arranging finances (49%). Two COVID-19-related incidents resulted in infecting 27 persons. Fifteen instances of possible COVID-19-related mishaps were averted. CONCLUSIONS: We observed a decrease in the operations of the department without any adverse impact in postoperative outcomes. While challenging, treating cancer adequately during COVID-19 can be accomplished by adequate screening and testing, and religiously following the prevention guidelines.

Oncocytic mucoepidermoid carcinoma (OMEC) of the parotid gland in a 12-year-old patient: A diagnostic challenge on cytology.

Mucoepidermoid carcinoma is the most common malignant salivary gland neoplasm comprising approximately 10% of all tumours of the major salivary gland. Owing to a plethora of morphological variations, it poses a diagnostic challenge on fine-needle aspiration cytology. Oncocytic variant of mucoepidermoid carcinoma is a rare subtype seen in the age group of 20-80 years. It is crucial to make the correct diagnosis on cytology as it has therapeutic implications. Oncocytes can be present in a wide range of salivary gland lesions ranging from non-neoplastic conditions to benign and malignant lesions. We report a case of oncocytic mucoepidermoid carcinoma of the parotid gland in a 12-year-old boy which is the youngest age reported for the same. On cytology, this case was initially diagnosed as Warthin's tumour and was supported by radiology. However, histomorphological findings clinched the diagnosis of an oncocytic variant of mucoepidermoid carcinoma with the aid of immunohistochemistry.