Pathology and Microbiology

From Editor's desk Ranjan Agrawal Indian Journal of Pathology and Microbiology 2019 62(2):193-194

Expanding the scope of tumor budding Antonio D'Antonio, Alessandro Caputo Indian Journal of Pathology and Microbiology 2019 62(2):195-196

Prognostic value of lymph node ratio in cancer Asaranti Kar Indian Journal of Pathology and Microbiology 2019 62(2):197-198

Small round cell lesions of the bone: Diagnostic approach, differential diagnoses and impact on treatment Bharat Rekhi, Asit Mridha, Jayashree Kattoor Indian Journal of Pathology and Microbiology 2019 62(2):199-205 Small round cell lesions of the bone encompass a heterogeneous group of tumors and tumor-like lesions, including Ewing sarcoma, small cell osteosarcoma, mesenchymal chondrosarcoma, neuroblastoma, non-Hodgkin's lymphoma (NHL), “Ewing-like” undifferentiated round cell sarcomas, metastasizing small cell carcinoma, along with plasma cell dyscrasia and Langerhan's cell histiocytosis. At the same time, there are tumor mimics, for example, chronic osteomyelitis, which has overlapping radiologic features with Ewing sarcoma and a primary intraosseous NHL. An exact diagnosis necessitates integration of clinical, radiologic, pathologic, and ancillary test results, including immunohistochemical and molecular results. Currently, there are several immunohistochemical markers and specific molecular signatures, driving most of these tumors, available, for an exact diagnosis. This review focuses on a pragmatic approach towards uncovering specific small round cell lesions of the bone, emphasizing upon integration of traditional morphology with ancillary techniques, including immunohistochemical markers and molecular techniques, the latter, especially in cases of Ewing sarcoma, Ewing-like undifferentiated round cell sarcoma, mesenchymal chondrosarcoma, and neuroblastoma. Subsequent to the diagnostic approach, including an impact on treatment, individual intraosseous round cell lesions have been described in detail. The references include updated articles from PUBMED.

The diagnostic significance of trophoblast cell-surface antigen-2 expression in benign and malignant thyroid lesions Canan Sadullahoğlu, Alper Sayıner, Dinç Süren, Hülya Tosun Yıldırım, Döndü Nergiz, Cem Sezer, Mehmet Tahir Oruç Indian Journal of Pathology and Microbiology 2019 62(2):206-210 Context: Thyroid cancers are the most common malignancy of the endocrine system. Over-expression of trophoblast cell-surface antigen 2 (TROP-2) in various tumors has been found to correlate with poor prognosis and aggressive tumor behavior. Aims: The aim of this study was to evaluateTROP-2 expression in thyroid neoplasms. Subjects and Methods: This study contained 152 cases, including 48 follicular nodular disease (FND), 29 follicular adenoma (FA), 57 papillary thyroid carcinoma (PTC), 12 follicular thyroid carcinoma (FTC), 3 medullary thyroid carcinoma (MTC), 2 poorly differentiated thyroid carcinoma (PDTC) and 1 undifferentiated thyroid carcinoma (UDTC). TROP-2 expression was investigated via immunohistochemistry in sections prepared from paraffin blocks of the cases. Results: The cases comprised 32 (21%) males and 120 (79%) females with a mean age of 46.8 years (range, 15-85 years). TROP-2 expression was observed in 74.6% of the malignant lesions of the thyroid except for medullary carcinoma, poorly differentiated and undifferentiated thyroid carcinoma. Immunoreactivity was 3.4% in FA, 41.7% of cases with FTC and 81.8% in PTC follicular variant (PTC fv). The difference between FA/FTC and FA/PTC follicular variant were both significant (P < 0.005, P < 0.001, respectively). There was no difference between FTC/PTC fv (P = 0.089). Conclusion: TROP-2 can be considered a useful marker for distinguishing PTC fv cases from follicular nodular disease and follicular adenoma cases because of its high sensitivity in the identification of papillary carcinomas of the thyroid.

Incidental papillary thyroid microcarcinomas in thyroidectomy specimens: A single-center experience from Turkey Fatma Senel, Hatice Karaman, Aynur Aytekin, Güler Silov, Ali Bayram Indian Journal of Pathology and Microbiology 2019 62(2):211-215 Background: Papillary thyroid microcarcinoma (PTM) is a relatively common entity in the general population. PTM is often asymptomatic and is detected incidentally during the histopathological examination of thyroidectomy specimens from operations because of benign thyroid disease. Aims: The aims of the study are to determine the incidence of incidental papillary thyroid microcarcinomas (IPTMs) in our center, to examine the clinicopathologic characteristics of these tumors, and to present our experiences. Materials and Methods: This study includes 827 patients who underwent thyroidectomy operation in our center between January 2013 and June 2017 and were examined histopathologically in the Pathology Clinic. Patients' demographic characteristics, preoperative diagnoses, operative procedure, histopathological findings, and postoperative prognostic indexes are presented. Results and Conclusion: Of the 827 patients, 138 (16.6%) were diagnosed with a malignancy. Of these, 124 were papillary carcinoma, 5 were follicular carcinoma, 4 were lymphoma, 2 were medullary carcinoma, 2 were anaplastic carcinoma, and 1 was poorly differentiated carcinoma. The IPTM incidence rate was 8.01%; the multifocality and bilaterality rates were 23.3% and 13.3%, respectively. In 98.3% of IPTM cases, total thyroidectomies were performed, and in 1.7% of cases, subtotal thyroidectomy was performed followed by complementary thyroidectomy. No relapse or metastasis was detected in any of these cases. A careful histopathological examination of the thyroidectomy specimen is essential because IPTM is frequently skipped in fine needle aspiration cytology. We consider it best to perform total thyroidectomies because bilaterality and multifocality rates are high in IPTM. Long-term life expectancy in these tumors is quite good.

Evaluation of lymph node ratio and morphologic patterns of nodal reactive hyperplasia in primary organ malignancy Shinde V Sweety, Ashwini Sardar Narayankar Indian Journal of Pathology and Microbiology 2019 62(2):216-221 Background: Lymph node ratio (LNR) in cancer staging is the ratio of nodal metastases (LNM) to total nodes harvested (LNH). Reactive nodal hyperplasia can exhibit morphological patterns I to VI. Aims: To measure LNR and evaluate it with tumor stage, tumor grade, LN reactive patterns, and LN size. Setting and Design: Retrospective, observational study of 100 cancer resections including breast, gastrointestinal (GIT), genitourinary (GUT), and head, face, neck, and thyroid (HFNT). Materials and Methods: Total 1463 LNs were reviewed for metastases and reactivity patterns I–VI as per the World Health Organization (WHO) protocol. LNR was calculated from LNM and LNH. Statistical Analysis Used: Association between qualitative variables was assessed by the Chi-square test and Fisher's exact test, those between quantitative variables using the unpaired t-test and Mann–Whitney U test. Results: Mean LNH (23.7) was highest in HFNT and lowest (6.6) in GIT (P = 0.008). Mean LNR was highest (0.29) in breast and least (0.06) in HFNT (P = 0.861). Commonest LN reactive patterns were sinus histiocytosis (60), mixed (48), and follicular hyperplasia (46) (P = 0.000). Maximum cases of breast (59.6%), GUT (53.8%), and HFNT (45%) belonged to stage T2, while GIT (60.0%) to stage T3 (P = 0.000). Maximum well-differentiated cases belonged to HFNT (13, 59.0%), while moderately poorly differentiated cases of breast (38, 55.8% and 7, 70.0%) (P = 0.000). The largest and smallest metastatic LN was 2.4 cm and 0.4 cm (P = 0.009). LNs with thickened capsule showed nodal metastases in 75.7% (P = 0.003871). Conclusions: LNH and LNR cut-off values show organ-wise variation and need standardization. LNR shows stronger relation with tumor grade than tumor stage. Commonest LN reactive patterns include sinus histiocytosis and follicular hyperplasia. Thickened LN capsule strongly suggests nodal metastases. A longitudinal follow-up is warranted to study prognostic association between LNR and LN reactive pattern.

Tumor budding in infiltrating breast carcinoma: Correlation with known clinicopathological parameters and hormone receptor status Radhika Agarwal, Nita Khurana, Tejinder Singh, PN Agarwal Indian Journal of Pathology and Microbiology 2019 62(2):222-225 Introduction: Tumor budding (TB) is proposed as an essential step in the invasion and metastasis of various tumors. However, there is limited information about its role in breast cancer. This study was designed to assess the prognostic significance of TB in clinical practice. Objectives: To study and grade TB in patients with invasive breast cancer and to correlate it with known prognostic parameters. Materials and Methods: In this prospective study, 40 cases of invasive breast cancer were studied over a period of 1.5 years. Tumor buds were defined as comprising five tumor cells or less at the invasive front of the tumor. Cases were separated into two groups according to TB density as low grade and high grade. Significance and correlation between TB with established clinicopathological parameters and hormone receptor status were studied by Chi-square test. P value <0.05 was considered significant. Results: All 40 cases in this study were newly diagnosed cases, who did not receive any therapy. The majority of patients were premenopausal (55%), had small tumor size ≤5 cm (67.5%), had negative lymph nodes (67.5%), had grades 2 and 3 (75%), and presented in stages 1 and 2 pathological stage (62.5%). The majority were estrogen-receptor-negative (62.5%), progesterone-receptor-negative (65%), and human epidermal growth factor receptor-2-positive (52.5%). Higher grade TB was observed in larger tumor (P = 0.03), in higher stage (P = 0.046), and in tumor having lymphovascular emboli (P = 0.03) when compared with small size, lower stage, and tumor with no lymphovascular emboli, respectively. Conclusion: As higher grade TB was associated with larger, higher stage tumor, and in tumor having lymphovascular emboli, it can be recognized as an easily identifiable prognostic factor.

Immunophenotyping of male breast cancer - Experience at a tertiary care centre Sunil Pasricha, Meenakshi Kamboj, Parul Tanwar, Gurudutt Gupta, Manoj Panigrahi, Anila Sharma, Garima Durga, Anurag Mehta Indian Journal of Pathology and Microbiology 2019 62(2):226-231 Background: Male breast cancers (MBCs) are uncommon and account for 1% of all breast cancers. Medical conditions that increase the estrogen to testosterone ratio are implicated as the risk factors. Morphologically similar, but MBCs have biological differences compared with female breast cancer (FBC). Purpose: The present study was aimed to examine the immunophenotype of MBC, subsequent molecular subtypes, their association with clinicopathological features, and prognosis. Materials and Methods: We analyzed clinicopathological features of 42 cases of MBC, and classified them according to molecular classification using immunohistochemistry (IHC). This is the second largest study from India. Results and Conclusion: Median age of patients was 61 years (age range: 41-87 years). Invasive duct carcinoma comprised 95.2% of cases. Tumor grade II and III was seen in 50% and 47.6% of cases, respectively, and advanced stage disease (III/IV) was seen in 45.2% cases (n = 39). Estrogen receptor (ER) was positive in 97.6% cases, progesterone receptor (PR) in 83.3%, androgen receptor (AR) in 76.2%, HER2 in 4.8%, Cyclin-D1 in 92.9%, Bcl2 in 66.7%, GCDFP-15 in 23.8%, p53 in 16.7%, and Ki67 index was low (<14%) in 66.7% cases. Molecular subtyping of these cases revealed 64.3% of luminal A, 35.7% of luminal B, and no HER2 rich/driven category or triple negative case. There was no statistical significance between luminal A and B category pertaining to overall stage of tumor (P = 0.905). Lymph node metastasis was more commonly associated with luminal B category (P = 0.089). p53 positivity showed significant association with luminal A cases (P = 0.002) and nodal metastasis (P = 0.042). GCDFP-15 positivity showed significant association with higher tumor grade (P = 0.042) and stage (P = 0.047). Stage was the most significant prognostic marker (P < 0.0001). On follow-up (n = 27), all the six cases that showed recurrence/persistent disease were high stage (III/IV) on presentation.

Expression and clinical significance of B and T lymphocyte attenuator on CD4+ and CD8+ T cells from patients with pulmonary tuberculosis Xinghua Shen, Jianping Zhang, Peijun Tang, Huafeng Song, Xiaocao Liu, Ziyi Huang, Xueguang Zhang, Xuefeng Wang, Meiying Wu Indian Journal of Pathology and Microbiology 2019 62(2):232-238 Background: As an immune checkpoint, upregulation of B and T lymphocyte attenuator (BTLA) contributes to T-cell exhaustion in chronic infection. However, the characteristics of BTLA on T cells of patients with pulmonary tuberculosis (PTB) are still uncovered. Aims: The aim of the study was to elucidate the dynamics and clinical significance of BTLA expression on circulating CD4+ and CD8+ T cells of PTB patients. Materials and Methods: BTLA expression on T cells from PTB patients with smear positivity (n = 86) and healthy controls (HCs) (n = 40) were determined using flow cytometry. Results: The levels of BTLA expression on circulating CD4+ and CD8+ T cells of PTB patients with smear positivity were both upregulated, compared with HC. At the same time, the levels of BTLA expression on CD4+ and CD8+ T cells of patients with retreatment were both higher than that of those with initial treatment and gradually upregulated along with the increase of the bacillary load in sputum. In addition, the patients with lung cavity were discovered to present higher levels of BTLA expression on CD4+ and CD8+ T cells than those without lung cavity. Whereas we noted that there was no correlation between the levels of BTLA expression and the positivity or negativity of anti-Mycobacterium tuberculosis antibody. Conclusions: The levels of BTLA expression were upregulated on CD4+ and CD8+ T cells of PTB patients and associated with disease progression. Thereby, BTLA expression on T cells may be considered as a potential clinical indicator and utilized as a therapeutic target for PTB.