Amendments in surgical pathology reports: An 8-year institutional experience.

Surgical pathology reports may undergo revisions broadly categorized as addenda (supplementary information) or amendments (changes to finalized reports). Amendments indicate potential flaws in the diagnostic process and serve as important indicators of vulnerabilities in the histopathology workflow. This study analyzed the frequency and distribution of amendments in surgical pathology reports over 8 years to identify patterns highlighting opportunities for improvement. Surgical biopsies, excisions, and resections were included; cytology and molecular tests were excluded. Amended reports were categorized using previously used taxonomy documented in literature. Defects were classified as misinterpretations, misidentifications, defective specimens, or defective reports. Of 101,355 reports, 155 (0.15 %) were signed out with amendments. The amendment rate was approximately 1-2 cases per 1000 reports annually. Misinterpretations accounted for the majority (52 %) of amended reports, with undercalls (62 %) and overcalls (27 %) being predominant subtypes. Tumor staging was amended in 57 (37 %) cases, with 30 being upstaged and 11 downstaged clinically. The highest number of misinterpretation defects occurred in head and neck (36 %) and breast (21 %) specimens. Misinterpretation defects were present in 53 % of malignant cases versus 42 % of benign cases. In 18 cases, there were significant changes in pathological diagnosis (14 major and 4 minor). A standard taxonomy categorizing report defects is crucial for measuring and improving quality control. Accurate pathology reporting impacts patient care and guides workflow improvements. This taxonomy enables us to track variations and deficiencies in our pathology reporting processes in a reproducible way across the department.

Extradural spinal melanoma: is it primary or metastatic? A case report with a brief review of literature.

Melanocytic lesions involving the central nervous system are extremely rare and pose a diagnostic challenge owing melanoma being the third most common malignancy metastasizing to the spine. Morphology and immunohistochemistry are identical in both primary and secondary cases, and hence may not help in rendering a final diagnosis. Molecular alterations involving melanomas of the spine and melanomas elsewhere are distinct and help establish the appropriate diagnosis. We report an interesting case where molecular profiling of the tumor tissue helped render the final diagnosis.

Extranodal follicular dendritic cell sarcoma presenting as colonic mass: A diagnostic and therapeutic challenge.

Folliclular dendritic cell sarcoma (FDCS) is an extremely rare neoplasm originating from folliclular dendritic cells, both nodally and extranodally. Its primary presentation as a large colonic mass is rare and can be misdiagnosed as epithelial tumor/soft tissue tumor both clinically and through histomorphology. Due to its rarity and limited consensus guidelines about its management, it presents as a diagnostic and therapeutic challenge for pathologists and oncologists. However, accurate diagnosis is imperative due to its distinct prognostic and therapeutic implications. Herein we report, two cases of extranodal FDCS of colon with the aim of contributing to the management of this uncommon entity.

Diagnostic utility of LMO2 immunohistochemistry in distinguishing T-lymphoblastic leukemia/lymphoma from thymoma.

Distinguishing T-lymphoblastic leukemia/lymphoma (T-ALL/T-LBL) from thymomas (especially B1 or B2 type) can be challenging particularly in limited trucut biopsy material where appreciating architecture is difficult or the background epithelial component does not provide tangible evidence for definite diagnosis. As a pathologist, it is important to accurately diagnose these neoplasms because they have entirely distinct management protocols. Recent studies have reported that LIM Domain Only 2 (LMO2) is expressed in neoplastic lymphoblasts of T-ALL/T-LBL and is absent in thymocytes of normal thymuses or thymomas. An observational study was done to test the sensitivity and specificity of LMO2 in differentiating neoplastic lymphoblasts from thymocytes of thymomas/normal thymuses. Our study showed that LMO2 had sensitivity of 70% and specificity of 100% in diagnosing LBL. None of the thymomas (B1 or B2 type) showed expression of LMO2 in the neoplastic cells. LMO2 is a reliable marker of transformed T-cell precursors and should be routinely included in immunohistochemical panel when evaluating thymic/mediastinal neoplasms.

FH deficient uterine leiomyomas-a case series.

Introduction: Fumarate hydratase (FH) deficient uterine leiomyomas account for only 0.4 % of all uterine leiomyomas. They are characterized by some distinct histological features and may be associated with Hereditary leiomyomatosis and renal cell carcinoma (HLRCC) syndrome. Methods: Herein we present a series of five cases of FH deficient uterine leiomyomas in patients with a mean age of 30 years. All five patients underwent myomectomy. Three of these cases had an outside histopathologic diagnosis ranging from Smooth muscle tumor of uncertain malignant potential (STUMP) to Leiomyosarcoma while two cases were operated at our centre. All five cases were reported as suggestive of FH deficient leiomyomas and were advised germline testing along with genetic counselling. Results: Immunohistochemically four of the cases showed moderate to strong positivity for 2-SC with a complete loss or reduced expression of FH while one case showed absence of 2-SC staining. Discussion: Mutations in FH lead to reduced enzyme activity and accumulation of fumarate leading to a complete loss or aberrant reduced expression seen on immunohistochemistry, which confirms the diagnosis. It is important to differentiate it from a leiomyosarcoma or other malignant spindle cell tumors as these tumors follow a benign course. Their association with HLRCC also needs to be established for a suitable follow up since HLRCC-associated RCCs are often aggressive. Conclusion: Management of such leiomyomas is myomectomy or hysterectomy with advice of genetic testing to rule out HLRCC. Histomorphology and immunohistochemistry are imperative for a correct and timely diagnosis.

Primary pulmonary NUT midline carcinoma: An elusive and a rare diagnostic entity.

Nuclear protein in testis (NUT) midline carcinoma is a poorly differentiated tumor, is more common in midline anatomic sites, and involves young adults and children mainly. Primary pulmonary NUT midline carcinoma (NMC) is a rare and poorly defined entity in the prevailing literature. Being a highly aggressive and fatal neoplasm, it gets incumbent for the oncologists and the pathologists to be aware of this entity as it holds distinct management protocol and prognosis. Currently, BET inhibitors (BETi) and histone deactylase inhibitors have shown promising results as targeted therapies in clinical trials in head and neck NMC. We present a case report of NMC of primary pulmonary location in a young male with widespread bony metastasis.

Metastatic choriocarcinoma of the kidney in the absence of existing primary uterine tumor: A rare presentation.

Gestational choriocarcinomas are malignant neoplasms generally arising in the uterus in women of childbearing age. These are aggressive tumors with a high incidence of metastasis to vascular organs such as the lung, liver, and brain. Renal metastasis is extremely rare with low incidence rate and very few cases have been reported in literature. Hereby, we report a rare case of metastatic choriocarcinoma to the kidney in a 29-year-old female 10 years after resection of a hydatidiform mole. The histopathological diagnosis was made on a nephrectomy specimen. Pelvic and abdominal scan did not show any abnormal radiological findings. She was started on first-line chemotherapy and showed a complete response. In conclusion, gestational or primary nongestational choriocarcinomas should always be considered as a differential diagnosis in young females of reproductive age group presenting with flank abdominal pain, unexplained hematuria, and atypical renal tumor histology.

Application of lean methodology to frozen section workflow - An audit of present practices at a single large oncology center.

AIM: We conducted a pilot study to analyze the frozen section workflow in the histopathology department and to construct a future state map using Lean management for a better efficiency. METHOD: We analyzed the current state of frozen section workflow in our department, from receipt of the specimen to delivery of slides to the pathologist to communication of report to the surgeon by using value-stream mapping and spaghetti diagram. Further, with the help of the fishbone diagram and Pareto's chart, root cause analysis was done, and a future state map was created with help of a spaghetti diagram to eliminate the non-value-added steps. RESULTS: Our current value-stream map identified a total specimen processing time of 3393 min of which 2880 min were value-added, translating to a process cycle efficiency of 84.88 %. Also, with the help of tools of lean management we constructed a future state map to improve process cycle efficiency. CONCLUSION: In this study, we have attempted to use a few tools of lean management systems and suggested ways for continuous improvements that can be successfully implemented in histopathology laboratories.

Correlation NKX2.2 IHC and EWSR1 break-apart FISH in the diagnosis of Ewing sarcoma: Can combined NKX2.2 and CD99 immunoexpression obviate or minimize the need of FISH testing? First assessment study from Indian tertiary cancer care center.

Context: Ewing sarcoma (ES) are malignant small round cell tumors (MSRCT) characterized by rearrangements of EWSR1 gene. Although gold standard for diagnosis is detection of specific fusion genes by molecular testing, these ancillary tests are costly and only available in limited number of settings. There is a persuasive evidence for reliability of NKX2.2 immunohistochemistry (IHC) as a surrogate marker for EWSR1 gene rearrangement in ES. Aims: The aim of this study is to correlate the NKX2.2 immuno-expression with genetically confirmed ES cases and also to assess the reliability and accuracy of NKX2.2 along with combined positivity of NXX2.2 and CD99 in diagnosing ES and differentiating it from other relevant histological mimics. Settings and Design: The present study is a retrospective study conducted over a period of 6-year duration in a tertiary cancer care center. Methods and Material: We evaluated NKX2.2 immunoexpression in 35 genetically confirmed cases of ES and also in pertaining differential entities (n = 58) of ES including rhabdomyosarcoma (n = 20), lymphoblastic lymphoma (n = 14), Wilms tumor (n = 10), poorly differentiated synovial sarcoma (n = 4), small-cell osteosarcoma (n = 4), neuroblastoma (n = 5), and mesenchymal chondrosarcoma (n = 1). CD99 was performed in the category of MSRCTs showing NKX2.2 positivity to evaluate combined specificity for the diagnosis of ES. Results: Of the 35 genetically confirmed cases of ES, 29 cases (83%) showed NKX2.2-positive expression (83% sensitivity). Compared to ES, NKX2.2 was positive in only 05% cases (3/58 cases) of non-ES MSRCT. Only two of five cases of neuroblastomas and one case of mesenchymal chondrosarcoma showed NKX2.2 positivity. CD99 positivity was seen in 100% of ES and in the single case of mesenchymal chondrosarcoma. All five cases (100%) of neuroblastoma were negative for CD99. Conclusions: The presented study, which is the first from an Indian oncology center, showed NKX2.2 IHC is quite reliable in diagnosis of ES in the right clinicopathological context. With remarkable sensitivity and specificity of NKX2.2 IHC for diagnosis of ES, we propose that combined positivity of CD99 and NKX2.2 IHC can obviate or minimize the need of EWSR1 gene rearrangement molecular testing for diagnosis of ES.

Single Institute Experience with Neo-Adjuvant Chemotherapy and Interval Debulking Surgery in Advanced Endometrial Cancer.

Our study aims to review the role of neoadjuvant chemotherapy (NACT) followed by interval debulking surgery (IDS) in patients with advanced endometrial cancer. Patients with advanced endometrial cancer treated with NACT followed by IDS at our institute from January 2010 to January 2020 were recruited. Data pertaining to baseline patient characteristics, surgical details, histopathology/imaging reports, treatment and follow up details including the development of recurrence and death were collected from institutional database. Disease free survival (DFS) and overall survival (OS) were calculated using Kaplan Meier survival curves. We recruited 31 patients for our study. About 83.9% patients showed partial response and 6.4% patients responded completely to NACT with none of the patients developing disease progression. Complete cytoreduction was achieved in 90.3% patients, optimal cytoreduction in 3.2% patients while 6.5% patients had suboptimal surgery. On completion of primary treatment, complete remission was achieved by 80.6% patients while 16.1% patients had progressive disease. Median follow up period was 21 months (range 1- 61 months). During follow up period, 51.6% patients developed recurrent disease after achieving complete remission and 61.3% patients died of disease progression/recurrence. The median DFS and median OS of the cohort was 15 months and 21 months respectively. The 2 year DFS for the cohort was 34.1% and the 3 year OS was 30.5%. NACT followed by IDS is a reasonably good option for advanced stage endometrial cancer not amenable to primary surgery. Innovative treatments are warranted in this cluster of patients.

PD-L1 expression in muscle invasive urothelial carcinoma: Comparison of SP142 and SP263 assay.

Introduction: High-grade urothelial carcinoma has a different molecular pathway than superficial low grade urothelial carcinoma, and is characterized by genomic instability. The high tumor mutation burden leads to neoantigen formation, evoking an immune response. The immune response has been keenly studied in last two decades and programmed death ligand-1 (PDL-1) has emerged as acceptable immunohistochemical marker for assessment of response to therapy, prognostication and patient selection for immunotherapy. The targeting of PD-1 and PDL-1 by checkpoint inhibitors (CPIs) is an attractive strategy to unblock the inhibitor and induce cytotoxic cell death. However, the presence of complementary and companion diagnostic testing with multiple PDL-1 assays and platforms for various CPIs make a diagnostic quagmire. Thus, it is the need of hour to harmonize these assays. In this undertaken study we evaluated the concordance in PD-L1 expression between the two PD-L1 clones: SP263 and SP142, in treatment naïve muscle invasive bladder cancer (MIBC). Methods: We evaluated Ventana PD-L1 "SP263 and SP142" qualitative immunohistochemical assay using rabbit monoclonal anti-PD-L1 clones in evaluation of PDL-1 immunoexpression on Ventana autostainer platform. The study includes 30 muscle invasive urothelial carcinomas, with 10 of 30 having nodal metastasis. Results: SP263 assay was statistically more sensitive than SP142 for tumor cell (TC) scoring (P = 0.0009), whereas SP142 was more sensitive for immune cell (IC) scoring (P = 0.0067). There was no statistical significant discordance for TC or IC scoring between primary tumor and metastatic lymph node. Conclusion: PD-L1 testing status can be done on both primary tumor and metastatic site, however in metachronous metastatic setting, testing on recent metastatic site should be preferred. The harmonization of immunoexpression between 2 PD-L1 clones could not be achieved.

Molecular stratification of high-grade urothelial carcinoma by immunohistochemistry with its histomorphological and clinical correlation.

Introduction: Urothelial carcinoma poses a significant cause of morbidity and mortality. The recent classification of Tumors of Urinary System by World Health Organization fourth edition) has elucidated its molecular subtypes and its associated prognostic significance. Methods: We used immunohistochemistry marker expression (CK5/6, CK20, CD44, EGFR) as a surrogate marker, to stratify 150 cases of high-grade urothelial carcinoma into the intrinsic molecular subtypes. A correlation was also done with immunohistochemical markers p53, p21, E-cadherin and Ki-67. Results: On subtyping, 47.3% cases were basal, 42.7% luminal and 10% remained unclassified. We did not find GATA3 useful for molecular stratification in our study. Muscle invasion was seen in 59% of basal and 31% of luminal subtype (P = 0.016). Squamous differentiation was most commonly associated with basal subtype (P < 0.001). EGFR expression was seen in 62% of basal and 38% of luminal subtype (P = 0.014), and thus can be used as an additional marker for molecular stratification. Overexpression of p53 was seen in 64% cases of muscle invasive and 36% of non-muscle invasive high-grade carcinomas (P < 0.0001). An inverse relationship was observed between p53 and p21 immunoexpression (r = -0.494) (P < .0001). The overall survival at 1- and 2-year interval was more in the luminal subtype, suggesting an early mortality in basal group, (P = 0.827), and at 6 years both the groups had almost similar results. Conclusion: High-grade urothelial carcinoma is challenging in terms of therapeutic strategy. Increased understanding of underlying molecular basis helps identifying targetable treatment options, and newer biomarkers will enhance predictive and prognostic stratification.

Angiomatoid fibrous histiocytoma: Report of two cases, initially construed as sarcoma with unusual clinico-pathological features.

Angiomatoid fibrous histiocytoma (AFH) is a rare soft tissue tumor of uncertain differentiation with low metastatic potential, most commonly occurring in children, adolescents, and young adults, involving extremities. Due to its rare nature and diverse presentation, both clinically and morphologically, it is often misdiagnosed. It becomes important to correctly diagnose this lesion, given its distinct therapeutic implications. Here, we present the clinical, radiologic, and pathologic findings of two rare cases of AFH. Since AFH is a rare soft tissue tumor with low malignant potential, both pathologists and clinicians should be aware of this entity, when encountered with a soft tissue mass in extremities of a child or adolescent, so as to accord appropriate treatment in such cases.

Intraventricular metastasis from carcinoma breast masquerading as choroid plexus neoplasm: A case report.

Metastatic tumors in the brain represent the most common type of intracranial neoplasm, comprising 8-10% of all brain tumors. 30% of such tumors are primarily of breast origin in females. Brain parenchymal metastasis is the more common presentation. Intraventricular spread is rare, seen in less than 5% of cases in a metastatic scenario. Here, we report a case of 41-year-old female presenting with intraventricular brain metastasis in a follow-up case of carcinoma breast. Five years post-surgery, the patient presented with complaints of headache. On evaluation, magnetic resonance imaging (MRI) brain showed an intraventricular lesion in the fourth ventricle. She was operated on for the same and the biopsy revealed a tumor with a complex papillary pattern resembling choroid plexus papilloma. On immunohistochemistry (IHC), the tumor cells were positive for cytokeratin 7 (CK7), Epithelial membrane antigen (EMA), GATA3, and mammaglobin favoring a metastasis from breast origin. Hence, a possibility of brain metastasis should be kept in mind in patients presenting with solitary ventricular masses due to the lack of definite radiological characteristics in such locations and histological overlap. Also, organ-specific IHC is a must in today's evidence-based era as is reflected in our case.