Frequency of Programmed Death Receptor Ligand 1 Expression and Clinicopathological Factors Associated With Metastatic Triple-Negative Breast Cancer at a Tertiary Cancer Care Centre in South India.

Purpose Triple-negative breast cancer (TNBC) has a poor outcome compared to other subtypes. Immune checkpoint inhibitors (ICIs) have changed the treatment paradigm in metastatic diseases as well as in neoadjuvant setting. The response to these agents is affected by programmed death ligand 1 (PDL1) receptor expression which are reported objectively as a score. PDL1 is a prognostic marker also. Here, we present clinicopathological characteristics of metastatic TNBCs, report the proportion of PDL1 expression and its association with clinicopathological factors as well as survival. Methods This is a prospective study carried out at a tertiary cancer care centre in South India. Case records of all breast cancer patients treated in two years between August 2021 and July 2023 were reviewed, patients with metastatic TNBC were selected. Patient's characteristics, histological features, molecular profile, and treatment were analyzed. PDL1 testing was carried out on pretreatment tumor tissue sections with immunohistochemistry (IHC) (Dako 22C3). PDL1 staining was interpreted as negative or positive based on combined positive score (CPS), with an expression less than 10 considered negative. Results A total of 118 patients were analyzed. With a median age of 46 years (36-65 years), 52.5% (62/118) were premenopausal. Family history of Ca Breast was seen in 22% (26/118) patients. A majority of patients had left-sided tumor 55.9% (66/118). Visceral metastasis was more common 96.6% (82/118) than skeletal. Radical intent of treatment was adopted in 10% as patients had oligometastatic disease at presentation. As front-line treatment, anthracycline-based chemotherapy was administered to the majority 54.2% (64/118). The PDL1 expression with CPS more or equal to 10 was seen in 32.2% (38/118) patients. Survival was associated with menopausal status (p value=0.000) and family history (p value=0.028) but not with PDL1 nor sidedness in our study. Estimated survival at 12 months in PDL1 negative case is 10 ± 0.29 months, while in PDL1 positive case it is slightly more at 10 ± 0.75 months, but difference was not found to be statistically significant (p value=0.15). Conclusion TNBCs are highly aggressive subtype with limited treatment options and poorer outcomes. Our study shows PDL1 expression in 31.66% of the cases similar to other literature from India. Survival is associated with menopausal status and family history. No association was found between survival and PDL1 as well sidedness in our study.

Synchronous hepatocellular carcinoma and renal cell carcinoma: A cytological marvel.

Multiple primary synchronous tumours have always created an inquisitiveness among clinicians, radiologists and pathologists. The diagnosis invariably proposes a challenge to diagnosticians. The coexistence of a primary hepatocellular carcinoma (HCC) and renal cell carcinoma (RCC) is exceedingly rare, with countable number of cases being reported in literature. We report a pioneer case of 75-year-old male, having chronic hepatitis B, diagnosed with synchronous primary RCC and HCC in by fine-needle aspiration cytology (FNAC) and confirmed by immunohistochemistry.

BRCA1 expression, its correlation with clinicopathological features, and response to neoadjuvant chemotherapy in high-grade serous ovarian cancer.

AIM: In high-grade serous ovarian cancers (HG-SOC), BRCA1 mutation is one of the predominant mutations reported by various studies. However, the non-mutational mechanisms of BRCA pathway inactivation in HG-SOC are unclear. We evaluated BRCA1 inactivation by estimating its expression with its repressor, ID4, in primary and neoadjuvant chemotherapy (NACT)-treated HG-SOC tumors with known therapeutic responses. METHODS: We evaluated the expression pattern of BRCA1 protein by immunohistochemistry in 119 cases of HG-SOC from a hospital cohort consisting of primary (N = 69) and NACT-treated (N = 50) tumors. Histological patterns (SET), stromal infiltration by lymphocytes (sTILs), and chemotherapy response score (CRS) were estimated by microscopic examination. Gene expression levels of BRCA1, and its repressor ID4, were estimated by qPCR. The association of BRCA1 protein and mRNA with clinicopathological features was studied. The relevance of the BRCA1/ID4 ratio was evaluated in tumors with different CRS. RESULTS: BRCA1 protein expression was observed in 12% of primary and 19% of NACT-treated HG-SOC tumors. We observed moderate concordance between BRCA1 protein and mRNA expression (AUC = 0.677). High BRCA1 mRNA expression was significantly associated with a more frequent SET pattern (p = 0.024), higher sTILs density (p = 0.042), and increased mitosis (p = 0.028). BRCA1-negative tumors showed higher expression of ID4 though not statistically significant. A higher BRCA1/ID4 ratio was associated with high sTILs density in primary (p = 0.042) and NACT-treated tumors (p = 0.040). CONCLUSION: Our findings show the utility of the BRCA1/ID4 ratio in predicting neoadjuvant therapy response, which needs further evaluation in larger cohorts with long-term outcomes.

Angiomatoid Fibrous Histiocytoma, A Great Mimicker -A Short Series of 3 Cases with EWSR1 Fusion.

Angiomatoid Fibrous histiocytoma (AFH) is a rare soft tissue neoplasm that is often misdiagnosed initially. It is commonly encountered in the superficial extremities of children and young adults. It is composed of a nodular proliferation of bland looking spindled to ovoid cells, some with variant histology and characterized by EWSR1 fusion. We, herein, present three such cases, who presented with swelling in the right leg (case 1), right forearm (case 2), and right thigh (case 3). Case 2 presented in the fourth decade with a large swelling compared to the other two cases that presented in 3rd decade with a small swelling. Histologic examination of case 2 showed extensive myxoid changes making it diagnostically challenging. All three cases showed EWSR1 fusion with a break-apart probe. Follow-up was uneventful in all three cases. AFH, although it is a benign neoplasm, is a great mimicker of various low-grade spindle cell sarcomas. Awareness of this entity with its various histomorphological variants is necessary to accurately diagnose this lesion.

Extranodal natural-killer/T-cell lymphoma, nasal type: An immunomorphological study from a regional cancer institute in India.

Introduction: Extranodal natural-killer/T-cell lymphoma, nasal type (ENKTL), is a rare, aggressive, predominantly extranodal non-Hodgkin lymphoma (NHL) of putative natural-killer (NK) cell and rarely T-cell origin, always associated with Epstein-Barr virus (EBV) infection and characterized by highly distinctive histopathological features with predilection for the upper aerodigestive tract. While the nasal cavity is the prototypical site, less frequently extranasal ENKTL can also occur. The objective of this case series is to study the immunomorphological features of ENKTL from a tertiary cancer centre as the data are sparse from India despite it being a distinct entity with characteristic clinicopathological features. Methods: We identified 11 cases of ENKTL from the departmental archives between January 2015 and June 2018. The clinicopathological and immunohistochemistry (IHC) findings of these tumors were analyzed. EBV encoded RNA (EBER) in situ hybridization (EBER-ISH) for EBV was done in eight cases. Results: The disease was more common in males (male: female ratio 1.8:1) with the mean age of 45 years (range 31-65 years). Sinonasal region was the most common site with 9 cases and skin and penis were involved in one case each. The patient with penile involvement on further investigations was found to have occult nasal involvement, Histomorphological features such as angiocentricity/angioinvasion was seen in seven cases (63.6%) and significant necrosis was present in all 11 cases (100%). All cases were uniformly positive for cytoplasmic CD3 and CD56 with high Ki67 proliferating index and EBER-ISH test for EBV was positive in all the eight cases. Conclusion: ENKTL is an aggressive NHL and should be differentiated from other T- and B-cell lymphomas as the prognosis and therapy differ. Nasal biopsies showing predominant necrosis and atypical lymphoid cells with angiocentricity must raise the suspicion of ENKTL and should be confirmed by immunomorphological and molecular studies.

Discordance in clinical versus pathological staging in breast cancer: Are we undermining the significance of accurate preoperative staging in the present era?

BACKGROUND: The present era of individualized treatment for breast cancer is influenced by the initial disease status including the anatomical extent, grade, and receptor status. An accurate preoperative staging is the basis of treatment planning and prognostication. Our study aims to determine the discordance between the preoperative clinical and the postoperative pathological stages of breast cancer patients. METHODOLOGY: The medical records of all non-metastatic breast cancer patients from January 2017 to December 2018 who underwent upfront surgery were reviewed. They were staged as per the eighth AJCC and the concordance between the clinical (c) and pathological T (tumor), N (nodal), and final AJCC stage was studied. A Chi-square test was used to determine factors that significantly correlate with disease discordance. RESULTS: A total of 307 breast cancer patients were analyzed. Among these, 43.3% were hormone receptor-positive, 30.6% were Her2 positive and 26% were triple-negative. Overall stage discordance was seen in 48.5% (n = 149) patients (upstaging in 22.1%, downstaging in 26.4%). The discordance rate was 48.9% for T stage (cT versus pT) and 57.4% for N stage (cN versus pN). Among patients with clinically node-negative disease, 53.4% were found to have positive nodes on histopathology, while 27.2% had vice versa. Overall, the factors associated with upstaging were ER-positive, Her2 positive and triple-negative status (all p < 0.05), while none of the factors showed significant association with downstaging. CONCLUSIONS: About half of breast cancer patients had discordance between clinical and pathological staging with higher discordance in the nodal stage. This changes the disease prognosis, and may also affect the offered surgical treatment and radiotherapy. Thus highlighting the need for a precise pre-operative staging. Also, this information will aid clinicians in discussions with patients, keeping in mind the likelihood of change in disease staging and management.

Primary mucinous carcinomas of the lung: Clinical characteristics and treatment outcomes.

INTRODUCTION: Invasive mucinous adenocarcinoma (IMA) of the lung is a distinct histologic variant of adenocarcinomas comprising about 2%-10% of lung adenocarcinomas. A large proportion of IMAs carry KRAS mutations and only rarely epidermal growth factor receptor (EGFR) mutations or ALK/ROS translocations; thus, most cases are not amenable for targeted therapy at present. This study was conducted to elicit the unique clinicopathological characteristics of IMA. MATERIALS AND METHODS: Medical records of patients diagnosed with IMA by needle biopsy at Kidwai Cancer Institute, Bangalore, from 2013 to 2018, were retrieved and reviewed. Statistical analysis was performed using SPSS version 23.0 (IBM Corp., Armonk, NY, USA). RESULTS: Four hundred and ninety cases of needle biopsy of the lung were diagonosed at our institute between January 2013 and December 2018. Nine cases (1.8%) were diagnosed as IMA. The median age of presentation was 59 years. Six (66.7%) were current smokers with pack-year > 20. Three (33.3%) of the cases were initially misdiagnosed as pneumonia in view of computed tomography findings. The lung was the most common site of metastasis (77.8%). Serum Carcinoembryonic Antigen (CEA) was elevated in six cases (66.7%). None of the cases had any driver mutations in EGFR gene or ALK and ROS1 translocations. All cases were treated with pemetrexed-carboplatin doublet followed by pemetrexed maintenance till progression. The median progression-free survival (PFS) was 15 months (range: 5-18 months). Docetaxel was given as the second-line chemotherapy in all progressed patients. Best response noted was stable disease, seen in 4 (57.1%) cases. The median PFS for docetaxel was 6 months (range: 3-8 months). The median overall survival was 22 months (range: 9-27 months). Patients with initially raised CEA at progression had a serial rise in serum CEA. CONCLUSIONS: IMA is rarely diagnosed on needle biopsies due to insufficient tissue. They mimic pneumonia on imaging, thus delaying diagnosis. EGFR mutations, ALK, and ROS1 translocations are usually negative making them ineligible for tyrosine kinase inhibitors. Response to chemotherapy is modest.

Spectrum of metastatic neoplasms of the brain: A clinicopathological study in a tertiary care cancer centre.

BACKGROUND: While brain metastases (BM) are the most common causes of neurologic disorders in patients with known systemic malignancies, they can often be the initial manifestations of an undetected primary elsewhere. BM are major causes of morbidity and mortality in cancer patients. AIMS: We describe a mixed population (data from both retrospective and prospective collection) having a BM from a solid tumor. We report the percentage distribution of the most frequent types of BM, confirming the data published in the literature. This paper may play a role in presenting the Southeast Asian reality compared with the Western countries. SETTING: A tertiary-care cancer centre. MATERIALS AND METHODS: Data for 4 years were retrieved from the records of the Department of Pathology of our institute. Hematolymphoid and meningeal tumors were excluded. Hematoxylin and eosin (H and E) stained slides were reviewed, and in cases with an unknown primary, immunohistochemistry (IHC) was advised. The panel of markers was chosen based on the histomorphology on H and E sections. IHC was done in cases with an unknown primary where paraffin blocks were available. RESULTS: Lung cancer was found to be the most common primary malignancy (n = 30; 48.4%) followed by breast cancer (n = 13; 21%), colorectal cancer (n = 6; 9.6%), and skin cancer (melanoma) [n = 3; 4.8%]. CONCLUSION: The incidence of BM from lung and breast cancer was similar to that seen in the Western studies. However, BM from colorectal cancer and melanoma show a higher and lower incidence, respectively, in comparison with the Western literature.

Estrogen receptor, Progesterone receptor, and human epidermal growth factor receptor-2 status in breast cancer: A retrospective study of 5436 women from a regional cancer center in South India.

AIM: The aim of the study was to analyze the estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 (HER2) status over 7 years in South Indian women with breast cancer. Further analysis of a subgroup was done to study clinically defined subtypes and the role of preanalytical factors in needle core biopsies (NCBs) and excised specimens. MATERIALS AND METHODS: This was a retrospective study from January 2010 to December 2016. Patients diagnosed with invasive breast cancer and available immunohistochemistry (IHC) reports of ER, PR, and HER2 status were analyzed. The cases for the year 2016 were analyzed further to observe the impact of preanalytical factors on the IHC staining patterns and surrogate status. RESULTS: A total of 5436 patients were included with a median age of 48 years. Among these, 65% were ≤ 55 years. The overall incidence of hormone receptor (HR)-positive patients was 48%; HER2 positive, 15%; and triple-negative breast cancer (TNBC), 37%. The incidence of HR positive, HER2 positive, and TNBC were 45%, 16%, and 39% and 53%, 13%, and 34% in patients <56 years and over 55 years, respectively (P < 0.001). There was an increase in HR positivity and decrease in TNBCs over time. There was no significant difference in the staining patterns in NCBs and excised specimens. CONCLUSION: With time, there is an increase in hormone-positive tumors which may be attributed to better IHC techniques and tissue handling. There was no statistical difference in the patterns of ER, PR, and HER2 immunostaining in core biopsy and excised specimens.

Clinicopathological Profile and Outcomes of Follicular Dendritic Cell Sarcoma of the Head and Neck Region - A Study of 10 Cases with Literature Review.

INTRODUCTION: Follicular Dendritic Cell Sarcomas (FDCS) are rare disorders of the lymph node and soft tissues. Accurate characterization of these neoplasms is important in planning optimal treatment given its potential for recurrence and metastasis. AIM: To analyse the clinicopathological profile and outcomes of a series of 10 cases of follicular dendritic cell sarcoma arising in the head and neck region diagnosed at our regional cancer centre. MATERIALS AND METHODS: A series of 10 cases of FDCS of the head and neck region from the hospital registry of head and neck cancers diagnosed between 2007 and 2013 were collected and analysed retrospectively. Clinical details, pathologic features, immuno-phenotypic profile, treatment approach and outcomes over a period of 5 years were noted. The Recurrence Free Survivals (RFS) of all the patients were recorded. RESULTS: The median age of the patients was 57 years and the mean age was 50.9 years. Male: female ratio was 7:3. In eight of the 10 patients, the tumours were located in the tonsils. All the tumour cells showed diffuse cytoplasmic CD21 and CD23 positivity by IHC. All the 10 cases underwent surgical excision of the tumour and three cases underwent additional neck dissection for cervical lymph node enlargement. All the patients with high grade tumours were uniformly managed with Tri-modality treatment (Surgery followed by radiotherapy and chemotherapy). The overall recurrence rate was 70%. The mean and median recurrence free survival was 39.6 and 44 months, respectively. Two of the three patients who remained recurrence free at the end of the 60 months had low grade tumours. CONCLUSION: Early recognition of follicular dendritic cell sarcomas requires a high index of suspicion and bi-modality or tri-modality treatment may cure a subset of low and high grade tumours respectively and prolong recurrence in a large subset of patients. Surgery is the mainstay and the definitive modality of treatment; the advantages and benefit of adjuvant radiotherapy and chemotherapy are yet to be established. Tri-modality management may have a role in high grade patients which needs to be substantiated in future studies.

Calcium-Oxidant Signaling Network Regulates AMP-activated Protein Kinase (AMPK) Activation upon Matrix Deprivation.

The AMP-activated protein kinase (AMPK) has recently been implicated in anoikis resistance. However, the molecular mechanisms that activate AMPK upon matrix detachment remain unexplored. In this study, we show that AMPK activation is a rapid and sustained phenomenon upon matrix deprivation, whereas re-attachment to the matrix leads to its dephosphorylation and inactivation. Because matrix detachment leads to loss of integrin signaling, we investigated whether integrin signaling negatively regulates AMPK activation. However, modulation of focal adhesion kinase or Src, the major downstream components of integrin signaling, failed to cause a corresponding change in AMPK signaling. Further investigations revealed that the upstream AMPK kinases liver kinase B1 (LKB1) and Ca(2+)/calmodulin-dependent protein kinase kinase ß (CaMKKß) contribute to AMPK activation upon detachment. In LKB1-deficient cells, we found AMPK activation to be predominantly dependent on CaMKKß. We observed no change in ATP levels under detached conditions at early time points suggesting that rapid AMPK activation upon detachment was not triggered by energy stress. We demonstrate that matrix deprivation leads to a spike in intracellular calcium as well as oxidant signaling, and both these intracellular messengers contribute to rapid AMPK activation upon detachment. We further show that endoplasmic reticulum calcium release-induced store-operated calcium entry contributes to intracellular calcium increase, leading to reactive oxygen species production, and AMPK activation. We additionally show that the LKB1/CaMKK-AMPK axis and intracellular calcium levels play a critical role in anchorage-independent cancer sphere formation. Thus, the Ca(2+)/reactive oxygen species-triggered LKB1/CaMKK-AMPK signaling cascade may provide a quick, adaptable switch to promote survival of metastasizing cancer cells.

Ureteric lymphoma as a rare cause of right lower ureteric obstruction.

Primary lymphoid neoplasms of the urinary tract are exceedingly rare, with only 21 cases being reported and comprising less than 5% of all primary extranodal lymphomas. We report a case of a 45-year-old man who presented with right flank pain and weight loss, and who was found to have a stricture in the right lower ureter causing ureteral obstruction. Histopathology revealed lower ureteric non-Hodgkin lymphoma, which, on further evaluation, was found to be isolated ureteric lymphoma. The patient was doing well after six cycles of R-CHOP chemotherapy. This case is being reported as a rare cause of distal ureteric obstruction.

A rare case of primary anaplastic large cell lymphoma of the central nervous system.

Primary central nervous system lymphoma (PCNSL) is an uncommon variant of extranodal non-Hodgkin's lymphoma, confined to the central nervous system (CNS) and is usually seen in immunocompromised patients. The vast majority of cases are of the B-cell type and T-cell PCNSL is rare. Here, we report an 18-year-old male who presented with fever, headache, and history of seizures. On evaluation, he was found to have a left parieto-occipital mass which was completely excised. Histopathology was suggestive of a T-cell neoplasm and immunohistochemistry showed tumor cells positive for leukocyte common antigen, anaplastic lymphoma kinase (ALK), CD30, and CD4 which confirmed the diagnosis of ALK-positive anaplastic large cell PCNSL. There was no evidence of disease outside the CNS. He was started on the DeAngelis protocol for PCNSL. To the best of our knowledge, only 27 cases of anaplastic large cell PCNSL have been previously reported in literature.

Sarcomatoid carcinoma of penis with bilateral inguinal metastases-a case report and review of literature.

Sarcomatoid carcinoma or carcinosarcoma of the penis is a rare entity with 36 cases reported in the literature. A 61-year-old male presented with swelling in the glans and shaft of the penis with bilateral inguinal lymph node metastases. He underwent total penectomy with bilateral inguinal block dissection. Histopathology revealed sarcomatoid carcinoma of the Penis with bilateral inguinal lymph node metastases. The patient later developed bilateral lung metastases in 6 months and was succumbed to death. Sarcomatoid carcinoma or carcinosarcoma is a rare malignancy with poor prognosis.

Floor-of-mouth metastasis in colorectal cancer.

Colorectal cancers have potential for lymphatic and hematogenous metastases. Surgery is the definitive treatment, but the prognosis can be improved with the addition of chemotherapy, radiotherapy or both. However, the incidence of recurrence, both local and distant, remains significant. Distant metastases occur most often in the liver and lung; however, metastases to bone, adrenals, lymph nodes, brain, skin and the oral region have been reported. Metastases to the oral region are uncommon and may occur in the oral soft tissues or jaw bones. The prognosis in such patients is usually very poor. We report a case of colorectal carcinoma with metastasis to the floor of the mouth. This is probably the first reported case of metastasis to the floor of the mouth in a patient with colorectal cancer.

Ovarian sex cord tumour with annular tubules diagnosed by fine needle aspiration cytology--a case report.

Sex cord tumor with annular tubules (SCTAT) is a rare ovarian neoplasm with distinctive morphological features whose cytological features have rarely been described. We report a case of SCTAT diagnosed on fine needle aspiration cytology (FNAC) with a brief review of literature. A 35 year old female presented with recurrent abdominal mass. Fine needle aspiration was done under ultra sound guidance. Cytology smears showed three dimensional tubular structures, metachomatic hyaline masses and uniform neoplastic cells dispersed and in cohesive clusters. Cell block study showed the characteristic simple and complex tubules leading to the diagnosis. The cytological findings of a rare ovarian neoplasm are described, which is only the third such report in English literature. The cytologic features of ovarian SCTAT are as distinctive as its histologicfeatures. Cell block study brings out the distinctive architecture of the tumor and helps in differentiating it from other closely related tumors.