Impact of Surgical Timing (Primary, Delayed, or Second Look) on Surgical Morbidity and Outcomes in Malignant Germ Cell Tumor of the Ovary in Children.

BACKGROUND: Malignant ovarian germ cell tumors (MOGCT) are rare in children. Surgery with or without chemotherapy is the primary treatment approach. This study aimed to analyze the impact of primary and delayed surgery on surgical morbidity and outcomes. Second-look surgery after inadequate surgical staging and the various components of surgical staging were also evaluated. METHODS: Children below 15 years with MOGCT treated between 2006 and 2022 were analyzed. A comparison of patients undergoing primary, delayed, and second-look surgery was performed. RESULTS: 118 patients with a median age of 12 (0.11-15) years were eligible. Forty patients underwent primary, 51 delayed, and 27 second-look surgeries. Overall complications, including tumor rupture, blood loss, and adjacent organ removal, were significantly higher in the primary compared to the delayed surgery group (p = 0.0001). Second-look surgery conceded more blood loss (p = 0.0001), extended duration (p = 0.03), and complications (p = 0.004) than delayed surgery. The compliance with surgical guidelines was 100% for most components, with a positive yield rate of 10-80%. At a median follow-up of 5.2 years, the 5-year event-free survival (EFS) and overall survival (OS) for the entire cohort are 86% and 89%, respectively. The OS and EFS did not differ by the timing of surgery, although the second-look surgery demonstrated relatively inferior outcomes consequential to initial suboptimal surgery. CONCLUSIONS: MOGCT shows favorable outcomes. Delayed surgery after chemotherapy in appropriately selected patients minimizes the morbidity of surgery with similar outcomes compared to primary surgery. An optimal initial surgery is essential since second-look surgery produces significant morbidity. Prognosis Study, Level II evidence.

External Quality Assurance Helps Improve Infrastructure for Testing Breast Biomarkers Across a Lower- and Middle-Income Country: Our Experience With Breast Biomarker Testing in the National Cancer Grid External Quality Assurance System in India.

CONTEXT.­: Biomarkers in breast cancer need strict monitoring given their role in patient management. OBJECTIVE.­: To study the impact that regular participation in the National Cancer Grid (NCG) external quality assurance (EQA) system has on concordance rates for biomarkers in breast carcinoma. DESIGN.­: Tissue microarray (TMA) containing breast carcinomas was circulated to participating laboratories that performed immunohistochemistry for breast biomarkers. The returned TMAs were then assessed for test concordance. RESULTS.­: A total of 105 laboratories participated in the estrogen receptor (ER) and progesterone receptor (PR) EQA system cycles, and 99 centers participated in the human epidermal growth factor 2 (HER2) EQA system. In the ER EQA in the first cycle only 1 laboratory had a 100% concordance, which improved to 59 of 77 (76.6%) and 85 of 97 (85.9%) in the fourth and fifth cycles, respectively. In the PR EQA the 100% pass rate jumped from zero to 52 of 76 (68.4%) in the fourth cycle and 86 of 97 (88.6%) in the last cycle. For HER2 EQA, the 100% pass rates were seen in 7 of 23 laboratories (30.4%) in the first cycle, 49 of 78 laboratories (62.8%) in the fourth cycle, and 48 of 94 laboratories (51.1%) in fifth cycle of EQA. Centers who participated in the NCG EQA system for a longer period often changed testing methodology, with consequent improvement in their laboratory concordance rates. An increasing trend for the use of automated platforms and of the US Food and Drug Administration-approved antibody for HER2 testing was observed. CONCLUSIONS.­: Our experience demonstrates that laboratory performances improve with participation in an EQA system even in less perfect settings, and this drives the placement of more proficient practices across the country.

Spermatocytic tumor of testis: A case series of 26 cases elucidating unusual patterns with diagnostic and treatment dilemmas.

Background: Spermatocytic tumours are a rare subset of testicular tumours seen in elderly patients with distinct clinicopathological features and a favourable outcome. The typical presentation and characteristic histological features usually suffice for the diagnosis. Most of the cases are amenable to surgical excision. However, occasional cases which have a sarcomatous transformation may behave more aggressively and warrant adjuvant therapy. Methods: We present the clinicopathological features of a series of 26 cases diagnosed as Spermatocytic tumour at our tertiary cancer institute from 2002-2019. Results: Twenty-four of these cases had the typical cytological features of a spermatocytic tumour while two cases showed sarcomatous change, one with rhabdomyosarcomatous differentiation and the other being an undifferentiated spindle cell sarcoma. Although the tumor can show varied patterns, the tripartite cytomorphology is typical in all cases. Conclusions: Careful note of these patterns and variations in histology is essential to prevent an erroneous diagnosis of other testicular neoplasms and guide the therapy.

Reclassification of Salivary Gland Aspirates Based on "The Milan System for Reporting Salivary Gland Cytology": A Five-Year Retrospective Study.

Introduction: The Milan System for reporting salivary gland cytopathology helps standardize reporting systems across institutions, improve communication between clinicians and pathologists and guide the clinical management of patients. Aims: This study was undertaken to evaluate the utility of the Milan system classification in cytology reporting. Settings and Design: The present study is a retrospective study conducted over a period of five years in tertiary care centre. Methods and Materials: All the cases of salivary gland aspirates were reviewed and reclassified into six diagnostic categories according to the Milan system of reporting salivary gland cytology (MSRSGC). Cytological diagnosis was correlated with the histopathological diagnosis wherever available. Results: A total of 258 cases were classified using the Milan system as non-diagnostic (20.9%), non-neoplastic (26.3%), atypia of undetermined significance (4.7%), neoplasm benign (37.5%), neoplasm of uncertain malignant potential (3.5%), suspicious for malignancy (0.4%), and malignancy (6.6%). Cytohistological discordance was noted among 8/76 cases (10.5%). The sensitivity and specificity of FNAC were 75% and 98.5%, respectively. The risk of malignancy was 14.2% for Category I, 9% for II, 50% for III, zero for IVA and IVB, and 83.3% for category VI. Conclusions: The new classification system helps pathologists to standardize reporting leading to better clinical and surgical management.

The clinical challenges and dilemma in the management of uncommon maxillary sinus tumors - A report of two cases.

Maxillary sinus is the common site for the nose and paranasal sinus tumors with diverse histopathological types and the treatment for each may differ. Making a histopathological diagnosis on occasion can be challenging. We had two patients presenting with upper alveolus growth in whom establishing the histopathological diagnosis was challenging. Through clinical evaluation, imaging (computed tomography and/or magnetic resonance imaging) and identification of key histopathological features helped in the management of these patients.

Primary Alveolar Soft Part Sarcoma of Bone: A Rare Occurrence in 8 Patients, Posing a Diagnostic Challenge.

CONTEXT.­: Alveolar soft part sarcoma is a rare soft tissue tumor involving mainly deep soft tissue of the lower extremities. Primary bone involvement is extremely rare. OBJECTIVE.­: To discuss histopathologic and immunohistochemical features of alveolar soft part sarcoma along with challenges in diagnosis and management in the context of primary bone origin. DESIGN.­: Our study constituted 8 patients. Data were collected from the Tata Memorial Hospital, Mumbai, India, during a 10-year period. RESULTS.­: Five patients in our study were female and 3 were male. Their ages ranged from 13 to 56 years. Primary bone involvement was seen in the humerus, tibia, fibula, radius, calcaneus, and rib. Radiologic impression was that of a primary malignant bone tumor in all patients. Conventional histopathologic features were seen in 7 of 8 patients. Positive immunohistochemical expression for TFE3 was demonstrated in 6 patients. All patients had distant metastasis either at presentation or later in the course of the disease. Surgical excision of the primary tumor and adjuvant chemotherapy formed the basis of treatment. Four patients succumbed to disease and 2 were alive with disease. CONCLUSIONS.­: Rare occurrences of primary bone alveolar soft part sarcoma posed a diagnostic challenge in the form of differential diagnoses of metastatic tumors resembling it either morphologically or immunohistochemically. The combined application of clinical and radiologic features along with characteristic histomorphology and immunohistochemistry helps to arrive at a definite diagnosis of alveolar soft part sarcoma. Aggressive behavior of this tumor and its refractoriness to conventional chemotherapy were evident from our series.

Remote Reporting from Home for Primary Diagnosis in Surgical Pathology: A Tertiary Oncology Center Experience during the COVID-19 Pandemic.

BACKGROUND: The COVID-19 pandemic accelerated the widespread adoption of digital pathology (DP) for primary diagnosis in surgical pathology. This paradigm shift is likely to influence how we function routinely in the postpandemic era. We present learnings from early adoption of DP for a live digital sign-out from home in a risk-mitigated environment. MATERIALS AND METHODS: We aimed to validate DP for remote reporting from home in a real-time environment and evaluate the parameters influencing the efficiency of a digital workflow. Eighteen pathologists prospectively validated DP for remote use on 567 biopsy cases including 616 individual parts from 7 subspecialties over a duration from March 21, 2020, to June 30, 2020. The slides were digitized using Roche Ventana DP200 whole-slide scanner and reported from respective homes in a risk-mitigated environment. RESULTS: Following re-review of glass slides, there was no major discordance and 1.2% (n = 7/567) minor discordance. The deferral rate was 4.5%. All pathologists reported from their respective homes from laptops with an average network speed of 20 megabits per second. CONCLUSION: We successfully validated and adopted a digital workflow for remote reporting with available resources and were able to provide our patients, an undisrupted access to subspecialty expertise during these unprecedented times.

Unfavorable presentation but comparable outcome: Presentation and outcome of children with nodular lymphocyte predominant Hodgkin lymphoma from India.

BACKGROUND: Nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) is an uncommon subtype of Hodgkin lymphoma (HL) with few published studies in children, entirely from North America and Europe. We analyzed clinical features and treatment outcome of pediatric NLPHL. PROCEDURE: Children less than 18 years of age diagnosed after histopathology review to have NLPHL between June 1998 and August 2016 were retrospectively analyzed. Descriptive details of clinical presentation and treatment were collected, and outcomes analyzed using Kaplan-Meier survival analysis. RESULTS: Of the 42 patients with a confirmed diagnosis of NLPHL during this period, there was complete information on 35. Median age was 11 years (range 6-16 years), male:female ratio was 4.8:1, there were 15, 11, 6, and 3 patients with Stage I, Stage II, Stage III, and Stage IV disease, respectively. Six patients had B symptoms, 10 had bulky disease, and 3 had bone marrow as well as extranodal involvement. Histology was typical NLPHL in 23 and variant in 12. Twenty-nine received chemotherapy, 10 with additional radiation, 3 patients with early stage disease received only radiotherapy and three others underwent complete node resection alone. Median follow-up was 55 months (range 7-165 months), 5 year event-free survival (EFS) was 83.3%, and overall survival 97.1%. Variant NLPHL histology was associated with higher incidence of unfavorable presentation and lower EFS. CONCLUSIONS: NLPHL in India has an excellent outcome, despite a higher incidence of unfavorable presentations such as advanced stage disease, B symptoms, and bulky disease. Variant histology is an adverse prognostic factor.

Soft tissue tuberculosis - An unusual presentation of a common disease.

Tuberculosis (TB) has reached epidemic proportions in India with a myriad of clinical presentations. Extra pulmonary TB can present in a wide variety of clinical forms and its identification requires a high degree of clinical suspicion. Soft tissue infection by Mycobacteria is rare. The diagnosis is often not thought of owing to the rarity of this entity.

Programmed death-1 ligands PD-L1 and PD-L2 show distinctive and restricted patterns of expression in lymphoma subtypes.

The success of immunotherapy using immune checkpoint blockade in solid tumors and in relapsed/refractory classical Hodgkin lymphoma and chronic lymphocytic leukemia holds promise for targeted therapy in hematologic malignancies. Because efficacy of immunomodulatory therapy is correlated with numbers of cells that express programmed death (PD-1) ligands, we evaluated the expression of PD-L1 and PD-L2 proteins using immunohistochemistry in more than 702 diagnostic lymphoma biopsies. In classical Hodgkin lymphoma, PD-L1 and PD-L2 were expressed in 82% and 41% of cases, respectively, and PD-L1 but not PD-L2 expression correlated with Epstein-Barr virus in tumor cells. PD-L1 staining was detected in 80% of anaplastic large cell lymphoma, angioimmunoblastic T-cell lymphoma, and follicular dendritic cell sarcoma; 75% of nodular lymphocyte-predominant Hodgkin lymphoma; 53% of primary mediastinal large B-cell lymphoma; 39% of extranodal NK/T cell lymphoma; 26% of peripheral T-cell lymphoma; 10% of diffuse large B-cell lymphoma; and very rare examples of mantle, marginal zone, and small lymphocytic lymphomas. PD-L2 staining was present in 78% of primary mediastinal large B-cell lymphoma but in fewer cases in all other categories including 40% of follicular dendritic cell sarcoma and 7% of anaplastic large cell lymphoma. Our results confirm and extend prior studies of PD-L1 and provide new data of PD-L2 expression in lymphomas. The differential expression patterns in some tumor types and the expression of PD-L2 in the absence of PD-L1 raise the possibility of targeted therapy for additional subsets of patients with lymphoma.

Feasibility of Axillary Reverse Mapping and Clinicopathological Features Predicting ARM Node Metastasis in Breast Cancer-a Pilot Study.

The axillary reverse mapping (ARM) technique has been described as an attempt to map and preserve the upper extremity lymphatic drainage during axillary lymph node dissection (ALND) and/or SLNB. This technique is based on the hypothesis that the lymphatic pathway from the upper extremity is not involved by metastasis from primary breast cancer. The ARM node/s however, has been found, in various studies, to be involved with metastatic foci in patients with extensive axillary lymph node metastases. Therefore, the oncological safety of this procedure has not yet been determined. In this pilot study, we assessed the ARM node intraoperatively for various parameters and compared it to final HPR, to try and determine the oncologic safety of preserving the ARM node. Seventy-two breast cancer patients were screened for this prospective pilot study which was planned to recruit 20 patients. The study was initiated on May 2014, 20 patients were recruited till July 2015. Eligibility criterion was as follows: patients requiring primary axillary lymph node dissection based on a clinically positive axilla. Forty-five patients were ineligible because they had either received neoadjuvant chemotherapy or underwent previous axillary surgery or axillary radiation (exclusion criteria). Seven patients refused to give consent. ARM node identification rate was 75%. The most common location of the ARM node was lateral to the latissimus dorsi pedicle (42.10%), none of them being malignant. None of the oval or firm nodes were malignant. Tumor deposits were identified in 13%. Fine-needle aspiration cytology (FNAC) had 100% specificity, 94.4% negative predictive value, 100% positive predictive value, and 50% sensitivity. ARM is feasible using blue dye alone, with an acceptable identification rate. Location, consistency, and intraoperative FNAC of the ARM node, put together, may be reliable parameters to predict involvement of the ARM node with metastasis.

A simplified scoring system to document variant patterns in nodular lymphocyte predominant Hodgkin lymphoma.

This study sought to quantify variant patterns in nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) using a three tier scoring system assessing five parameters, namely: (a) percentage of nodularity scored from 100 % to < 75%, (b) T cell rich areas (< 20% to > 50%), (c) type of nodules, (d) dendritic network, intact or lost, and (e) extranodular distribution of lymphocyte predominant cells (< 15% to > 50%), with final scores from 0 to 10. In the 72 patients assessed, the 5-year disease-free survival (DFS) in patients with score ≤ 6 was 92% vs. 20% in those with scores > 6. The 5-year overall survival was 100% in patients with scores ≤ 6 and 87% in those with scores > 6. In the multivariate Cox regression analysis, scores > 6 and stage impacted DFS. This scoring system was effective in stratifying patients with NLPHL with variant patterns and could be used for the management of patients.

Origin Use of CD4, CD8, and CD1a Immunostains in Distinguishing Mycosis Fungoides from its Inflammatory Mimics: A Pilot Study.

UNLABELLED: Patch-stage/early mycosis fungoides (MF) is difficult to differentiate from benign dermatoses, despite several robust histologic criteria. Most studies include advanced lesions and data about early disease is limited. OBJECTIVES: (1) To compare the CD4:CD8 ratio in patch-stage MF versus inflammatory mimics. (2) To study patterns of CD1a expression in the epidermis and dermis in the two groups. MATERIALS AND METHODS: Twenty cases each of early MF and inflammatory dermatoses were selected. The diagnoses were established after clinicopathologic correlation, repeat biopsies, and follow-up. The inflammatory group included pityriasis lichenoides chronica, actinic reticuloid, lichenoid purpura, and various psoriasiform dermatoses. Immunohistochemistry was done for CD4, CD8, and CD1a. Epidermal CD4, CD8 cells were quantified and CD1a was graded semi-quantitatively in the epidermis and dermis. RESULTS: The average CD4:CD8 ratio was 4.2 in MF (range: 1-16.8), and 0.9 in inflammatory diseases (range: 0.43-5), which was statistically significant (P < 0.0001). None of the MF cases had a ratio <1. Four cases of pityriasis lichenoides chronica had a ratio >1. CD1a cells had a continuous or confluent epidermal pattern in almost all cases of MF, while they occurred as small or large groups in the dermis. In inflammatory dermatoses, there were either isolated or scattered CD1a+ cells in both epidermis and dermis. CONCLUSIONS: Elevated CD4:CD8 ratio favors MF. But there is an overlap in the lower range with pityriasis lichenoides chronica. These cases require good clinicopathologic correlation and follow-up. Patterns of CD1a expression are more reliable. Immunostains buttress morphology and are a valuable addition.

Extraocular sebaceous carcinoma: a series of three cases with varied presentation.

BACKGROUND: Extraocular sebaceous carcinomas are rare cutaneous malignancies that account for only about 25% of all sebaceous carcinomas. The most common site of occurrence is the head/neck region. They are aggressive neoplasms that possess metastatic potential to regional or distant sites. Wide local excision of the lesion with removal of regional lymph nodes is the usual mode of therapy. METHODS: We present a series of three cases of sebaceous carcinomas occurring in extraocular sites outside the head and neck areas, like the axilla, chest wall, arm and thigh. One of these cases had an associated colonic carcinoma and constituted Muir-Torre syndrome (MTS). Another case presented with a skin nodule and regional nodal metastasis. The third case had a history of recurrent similar lesions at the same site. CONCLUSION: Although rare, extraocular sebaceous carcinomas are seen at varied sites and frequently pose problems in diagnosis. A longterm follow-up of these cases is warranted due to their aggressive behaviour, risks of recurrence, metastasis and the possibility of development of visceral malignancies.

Segmental dilatation of sigmoid colon in a neonate: atypical presentation and histology.

Segmental dilatation of the colon is a rare disorder of colonic motility in children, often presenting with severe constipation in older infants, children, and occasionally adults. It may mimic the commoner Hirschsprung disease clinicoradiologically but differs in that the ganglion cell morphology and distribution are typically normal in the colon. We report a neonate with segmental dilatation of the sigmoid colon who had an atypical clinical presentation and describe certain abnormalities in bowel histology (hypertrophied muscularis propria, nerve plexus, and ganglion cells located within the circular layer rather than the normal myenteric location), for the first time in the English literature.

Assessment of HER-2/neu status in breast cancer using fluorescence in situ hybridization & immunohistochemistry: Experience of a tertiary cancer referral centre in India.

BACKGROUND & OBJECTIVES: Determination of HER2 status in breast cancer has become important to identify potential candidates for anti-HER2 therapy. In this study we compared fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC) for the determination of HER2 status in breast cancer patients referred to a tertiary care referral centre. METHODS: A total of 200 cases of invasive breast cancer were evaluated for HER2 status using IHC and FISH and results were compared. RESULTS: The IHC 3+ (93.9%) and IHC negative (85.9%) cases showed good concordance with the corresponding FISH results; while 66.6 per cent of IHC 2+ cases showed gene amplification by FISH. In addition, hormone receptor expression and HER2 gene status showed a statistically significant inverse association (P<0.05). INTERPRETATION & CONCLUSION: These findings reaffirm IHC as a prudent first-step to screen tissue samples for HER2 status and to determine suitability for technically demanding FISH test and the dual coloured FISH as a gold standard for determination of HER2/neu status in IHC equivocal cases of breast carcinoma.