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.

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.

Impact of 2018 ASCO/CAP guidelines on HER-2 reporting categories of IHC and reflex FISH in breast cancer.

Human epidermal growth factor receptor 2 (HER-2) is an established prognostic and predictive biomarker for breast cancer. To ensure accuracy and uniformity for HER-2 testing, ASCO/CAP published guidelines in 2007 which were updated in 2013 and recently in 2018. In this first study from Indian Oncology center, we evaluated the impact of 2018 ASCO/CAP guidelines. We found a substantial decrease in equivocal IHC cases (P-value < .00001). On reclassification, a total of 5.6% cases from equivocal and positive categories (2013 guidelines) shifted to the negative FISH result category (P-value < .0001), with adoption of 2018 guidelines and eliminated the double equivocal cases.

Impact of 2013 ASCO/CAP HER2 reporting guidelines in breast cancer: An assessment study from Indian oncology centre that primarily performs HER2 IHC testing with special emphasis on IHC equivocal category.

The ASCO/CAP guidelines for HER2 reporting in breast cancer published in 2007 and were updated in 2013 to assure that the right patient receives the targeted therapy. The updated guidelines have lowered the threshold for HER2 positivity criteria and altered the equivocal category for both IHC and FISH. This first study from India addresses the impact of these updated guidelines in the various reporting categories at a tertiary care centre. We compared the trend of HER2 IHC reporting 1 year before (Period A) and 1 year after (Period B) the implementation of updated 2013 ASCO/CAP guidelines. All HER2 equivocal IHC cases of post 2013 guidelines were reclassified as per 2007 guidelines to detect additional number of cases that have been put into equivocal category. Reflex FISH correlation was also assessed to detect any additional cases eligible for anti HER2 therapy with implementation of these updated guidelines. With implementation of updated 2013 guidelines, there was significant decrease in the number of cases scored as 1+ (from 30.7% to 20.6%; P value: .0001) while significant increase in number of 2+ cases (from 20.2% to 27.3%; P value: .004). Post 2013 guidelines, 39% (64 cases) of tumors were additionally put into the equivocal category which would have been considered as negative (score 1+) as per 2007 guidelines. The reflex FISH testing in these equivocal cases resulted in detection of only 1.5% of additional cases eligible for anti HER2 therapy. With implementation of updated 2013 guidelines, there is no significant increase in HER2 positivity trend. However, there is appreciable increase in IHC equivocal cases which subsequently led to increased reflex FISH testing without significantly contributing to the detection of additional eligible cases for anti HER2 therapy, but resulted in delaying of definite HER2 status along with financial implications.

Lymphoepithelial carcinoma of tongue - Devil in garbs of Hodgkin lymphoma: A case report and review of literature.

Lymphoepithelial carcinoma (LEC) of head and neck region predominantly arises in salivary gland, oral cavity, oropharynx, nasal cavity, paranasal sinuses, and larynx; those arising from tongue are rare. Morphologically, it is a poorly differentiated squamous cell carcinoma, with early regional and distant metastasis. Diagnosis of LEC can sometimes be challenging especially in small biopsy and more so when seen at unusual location. Combination of morphology and immunohistochemistry (IHC) helps the diagnosis. Herein, we report a rare third case of LEC arising from lateral border tongue, diagnosed in a 36-year-old male. The presented case highlights challenges faced during diagnosis in small biopsy. Treatment of LECs comprises of surgery followed by radiotherapy or combined chemoradiation. Though, almost 70% of LEC of oral cavity region present with cervical nodal metastasis, their prognosis remains favorable.

Adrenal ganglioneuroma with retroperitoneal lymph node metastasis: A rare scenario.

ABSTRACT: Ganglioneuroma (GN) is the most differentiated and benign variant of neuroblastic tumors, most commonly located in the posterior mediastinum, followed by the retroperitoneum and adrenal gland. Children of <10 years of age are more commonly affected than adults. Though benign, GNs can very rarely metastasize to regional lymph nodes or distant sites like liver, bone, spleen, and soft tissues. Metastatic lesions are assumed to represent neuroblastomas in which the metastasis and the primary tumor, both have matured. This differentiation can occur spontaneously or after treatment. We present a primary ganglioneuroma of adrenal gland in a 4-year-old child with nodal metastasis, without any blastemal component at any site.

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 Oropharyngeal SMARCA4-Deficient Carcinoma: Expanding the Diagnostic Spectrum in Head and Neck Cancer.

With the advent of molecular immunohistochemistry and next generation sequencing, Switch/sucrose non-fermentable (SWI/SNF) chromatin remodeling complex altered tumors have gained recognition recently. SWI/SNF related, matrix associated, actin dependent regulator of chromatin subfamily B member 1 (SMARCB1) and SMARCA4 are the primary SWI/SNF components altered in several recently described undifferentiated malignancies in head and neck region with predilection for paranasal sinuses in SMARCB1-deficient tumors and nasal cavity in SMARCA4-deficient tumors. However, to the best of our knowledge, SMARCA4-deficient tumors of the oropharynx have not been described. We present an unusual case of SMARCA4-deficient carcinoma of the oropharynx (palatine tonsil) which is the first case in the literature, expanding the topographic distribution of SMARCA4-deficient tumors in the head and neck region and emphasizing the importance of BRG1 as an essential immunohistochemical marker for the diagnosis of this distinct 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.

Spindle epithelial tumor with thymus-like elements (SETTLE): a diagnostic challenge with distinct therapeutic implication; case report.

Spindle epithelial tumor with thymus-like elements (SETTLE) is a rare malignant neoplasm of the thyroid gland which is believed to arise from intrathyroidal thymic tissue. It predominantly affects young adults and children presenting with a thyroid mass of variable duration and rarely occurs in adults. It has a high overall survival with a tendency for delayed metastasis. SETTLE is a biphasic lobulated tumor composed of spindle shaped cells along with glandular formations seen on histopathological examination. Despite its typical morphology it is commonly misdiagnosed on histopathology due to its rarity and overlapping morphology with other close mimics such as a carcinoma, synovial sarcoma and thymoma. Herein we report such a case occurring in a middle aged female presenting with a neck mass. She had an initial diagnosis of metastatic poorly differentiated squamous cell carcinoma possibly with an orophayngeal primary in view of co expression of CK, p40 and p16 on immunohistochemistry. The patient underwent surgical resection with modified neck dissection. On review at our hospital it was diagnosed as SETTLE and she remains disease free after a follow-up period of 1 year. Diligent histopathological examination espoused with a judicious panel of IHC markers in conjunction with clinicoradiological findings forms the mainstay of diagnosis. Diffuse and strong p16 immunoexpression has not been documented or evaluated in literature so far, and needs to be explored for its diagnostic utility in this rare entity.

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.

Fumarate hydratase-deficient renal cell carcinoma: an oncology care institutional experience.

Renal cell carcinoma (RCC) accounts for 2% of all cancer cases worldwide, and majority are sporadic. The latest World Health Organization (WHO) classification of renal cell tumors (fifth edition, 2022) has molecularly defined renal tumor entities, which includes fumarate hydratase (FH)-deficient RCC. FH-deficient RCC is an aggressive carcinoma caused by pathogenic alterations in FH gene, seen in 15% of patients with hereditary leiomyomatosis and renal cell cancer syndrome (HLRCC) syndrome. These tumors occur more frequently at a younger age and present at an advanced stage, carrying a dismal prognosis. We report a series of 10 cases of FH-deficient RCC. The mean age was 49.8 years, and all cases presented in advanced stages (III and IV). Morphologically, the cases had varied architectural patterns with characteristic eosinophilic macronucleoli and perinucleolar halo. On immunohistochemistry (IHC), all showed diffuse nucleo-cytoplasmic expression of S-(2-succino)-cysteine (2-SC), with loss of FH in seven cases. FH-deficient RCCs are aggressive neoplasms and can be diagnosed using specific IHC markers (FH and 2-SC). These patients should undergo germline testing for FH gene mutation, genetic counseling, and surveillance of family members.

Evaluation of Turnaround Times of Diagnostic Biopsies: A Metric of Quality in Surgical Pathology.

Introduction. Timely and accurate diagnosis of diseases is crucial for effective patient care. Turnaround time (TAT) in surgical pathology, defined as the time between accessioning the sample and reporting results, is a key performance indicator reflecting quality and efficiency. This study explores factors affecting TAT for diagnostic biopsies in a tertiary oncology hospital. Methods. A 1-month pilot study was conducted, focusing on 695 in-house diagnostic biopsies. Biopsies were categorized as routine (requiring only hematoxylin and eosin (H&E) staining) or complex cases (requiring additional tests). TAT was defined as the time between sample accessioning and report availability in the electronic medical record, with delays defined as exceeding 3 days for routine cases and 4 days for complex cases. Survival analysis using Kaplan-Meier plots was utilized to analyze TAT. Results. The overall mean TAT was 3.7 ± 2 days, with routine cases at 3.1 ± 2 days and complex cases at 4.8 ± 2 days (P < 0.001). Survival analysis revealed prolonged TAT for complex cases. Organ-specific analysis highlighted variations in TAT, with brain biopsies presenting the highest complexity and longest TAT. Surprisingly, malignant cases demonstrated slightly shorter TATs compared to benign cases (P = 0.026). Delays were observed in 34% of all cases. Conclusions. Laboratory TAT is crucial and is frequently used as a performance benchmark. We analyzed the various causes of delayed TAT in our hospital's histopathology department, with an emphasis on variables in the analytical phase. The results of this study demonstrate that cases involving ancillary techniques had significantly longer TATs compared to routine H&E cases.

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.

Collision Tumour of Combined Neuroendocrine and Squamous Cell Carcinoma of Nasal Cavity and Paranasal Sinus- Case Report and Review of Literature.

Background: There have been many disputes about the definition, diagnosis, therapy, and prognosis of collision tumours. Case Summary: We describe a rare patient with a collision tumour consisting of high-grade neuroendocrine carcinoma (NEC) and squamous cell carcinoma (SCC) in the right nasal cavity and paranasal sinus. She received surgery, concurrent chemoradiotherapy, and then two cycles of palliative chemotherapy. Follow-up at 26 months after diagnosis showed that this patient experienced a complete response with no signs of recurrence or metastasis. A literature review of previous 27 cases diagnosed with collision tumour of NEC and SCC in the head and neck was also undertaken. Conclusion: It is highly challenging to manage collision tumours because these are two morphologically and etiologically distinct tumours. Well-designed multimodality therapy including surgery and chemoradiotherapy might lead to a long survival in these patients.

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.