Advancements in diagnosing IgG4-related disease of the head and neck: Navigating diagnostic pitfalls.

IgG4-related disease (IgG4-RD) is an immune-mediated condition affecting nearly any organ. This review focuses on the nuances of diagnosing IgG4-RD affecting the head and neck. Salivary gland involvement, especially of the submandibular glands, often permits a definitive diagnosis on biopsy. However, elevated IgG4+ plasma cells are nonspecific and can be seen in chronic sialadenitis, lymphoma, and other mimics. Careful correlation of clinical and pathological findings is essential. Given the significant overlap with chronic sinusitis, IgG4-RD of the sinonasal region is difficult to diagnose histologically. Laryngeal and pharyngeal involvement appears rare as an isolated finding of IgG4-RD. Mastoid disease is uncommon and remains a diagnosis of exclusion. Thyroid manifestations pose challenges given unclear diagnostic criteria - Riedel's thyroiditis likely represents IgG4-RD, but the fibrosing variant of Hashimoto's thyroiditis as a form of the so-called 'IgG4-related thyroiditis' requires better characterisation. Eosinophilic angiocentric fibrosis, despite histologic similarities, only partially overlaps with IgG4-RD. This review aims to guide diagnosing IgG4-RD in the head and neck through a systematic, organ-focused discussion of the clinical context, the utility of immunostaining, histological mimics, and controversial issues that pose diagnostic pitfalls. Increased awareness of the nuances and difficulties diagnosing IgG4-RD affecting the head and neck will improve recognition of this protean disease.

Pathological N3 Stage (pN3/ypN3) Gastric Cancer: Outcomes, Prognostic Factors and Pattern of Recurrences After Curative Treatment.

BACKGROUND: pN3 or ypN3 stage gastric cancers (GCs) are known to have aggressive clinical behaviour. This study aimed to investigate factors affecting survival and pattern of recurrences of N3 stage GCs, treated with curative intent. METHODS: A total of 196 GC patients, operated on at the Tata Memorial Centre from 2003 to 2017 and reported as pN3 or ypN3 status on histopathology after D2 gastrectomy were included in this retrospective analysis. RESULTS: On multivariate analysis, use of NACT (neoadjuvant chemotherapy) and LN ratio (≤ 0.5/> 0.5) emerged as significant predictors for long-term survival. Patients who received NACT but were still harbouring N3 nodes (ypN3; n = 102) had a worse prognosis than those operated on upfront (pN3; n = 94), with a median survival of 19 months versus 24 months respectively (p = 0.003). The 5-year overall survival of the entire cohort was 16.3% (95% CI 12.8-19.8%), while 5-year disease-free survival (DFS) was 14.6% (95% CI 12.6-20%). Adjuvant chemoradiotherapy, though offered in a small number of patients (n = 38) resulted in improvement in DFS. Median DFS of adjuvant CT versus adjuvant CRT was 13 months versus 23 months (p = 0.020). The commonest site of relapse was the peritoneum (49.18%) and incidence of isolated loco-regional failure was 10.7%. CONCLUSION: In GCs with N3 stage determined after radical D2 gastrectomy, LN ratio of > 0.5 and ypN3 status are predictors of poor prognosis. Considering the high incidence of peritoneal and loco-regional relapse in these patients, the role of more radical surgery, adjuvant chemoradiotherapy after upfront resection and intraperitoneal chemotherapy should be evaluated in prospective randomized clinical trials.

Outcomes of rectal cancer patients with a positive pathological circumferential resection margin.

PURPOSE: Evidence-based management of positive pathological circumferential resection margin (pCRM) following preoperative radiation and an adequate rectal resection for rectal cancers is lacking. METHODS: Retrospective analysis of prospectively maintained single-centre institutional database was done to study the patterns of failure and management strategies after a rectal cancer surgery with a positive pCRM. RESULTS: A total of 86 patients with rectal adenocarcinoma with a positive pCRM were identified over 8 years (2011-2018). Majority had low-lying rectal cancers (90.7%) and were operated after preoperative radiotherapy (95.3%). Operative procedures included abdomino-perineal resections, inter-sphincteric resections, low anterior resections and pelvic exenteration in 61 (70.9%), 9 (10.5%), 11(12.8%) and 5 (5.8%) patients respectively. A total of 83 (96.5%) received chemotherapy as the sole adjuvant treatment modality while 2 patients (2.3%) were given post-operative radiotherapy and 1 patient underwent revision surgery. A total of 53 patients (61.6%) had recurrence, with 16 (18.6%), 20 (23.2%), 8(9.3%) and 9 (10.5%) patients having locoregional, systemic, peritoneal and simultaneous local-systemic relapse. Systemic recurrences were more often detected either by surveillance in an asymptomatic patient (20.1%) while local (13.1%) and peritoneal (13.2%) recurrences were more often symptomatic (p = 0.000). The 2-year overall survival (OS) and disease-free survival (DFS) of the cohort was 82.4% and 74.0%. Median local recurrence-free survival (LRFS) was 10.3 months. CONCLUSIONS: Patients with a positive pCRM have high local and distal relapse rates. Systemic relapses are more often asymptomatic as compared to peritoneal or locoregional relapse and detected on follow-up surveillance. Hence, identification of such recurrences while still salvageable via an intensive surveillance protocol is desirable.

Outcomes of radical surgical resections for nonmetastatic anorectal melanomas: Experience from a tertiary care centre.

AIM: The outcome of radical surgery in nonmetastatic anorectal melanoma (AM) patients is studied infrequently. Here, we aimed to explore the stage-wise outcomes and the impact of radical resections in these patients. METHODS: In this single-centre retrospective study, data of 154 eligible patients were recorded and analysed. Data were obtained from November 2010 to September 2019 with follow-up until November 2020. Overall survival (OS) and disease-free survival (DFS) was calculated by Kaplan Meir method and univariate analysis of prognostic factors by Cox regression. RESULTS: Of 154 patients, 110 were metastatic (stage III) and 44 were nonmetastatic (stage I:22, stage II:22) and underwent curative resections. Median follow-up was 48 months (14-119 months). A total of 39 patients underwent total mesorectal excisions (TME) and five transanal excision (TAE) were performed. Seven patients underwent extended resections. Stage I and II patients had 3- and 5-year OS of 40% and 36%; and DFS of 45% and 33.2%, respectively. Median OS and DFS were 31 and 24 months, respectively. Stage II (node-positive) patients had better median OS compared to stage III (21 vs. 4 months; p = 0.000), and 54.5% patients had recurrences, most commonly both systemic and nodal (45.83%). Median OS of patients without recurrence was 34 months. CONCLUSION: In this large surgical series of AMs, outcome in stage I and II patients was significantly better than stage III and patients with stage II disease can have acceptable oncological outcomes. Radical surgical resections with or without lymphadenectomy could be considered in these patients. The role of adjuvant systemic therapy and radiation needs to be explored as part of multimodality treatment.

Narrow band imaging observed oral mucosa microvasculature as a tool to detect early oral cancer: an Indian experience.

BACKGROUND: Narrow band imaging (NBI) is a novel method with the potential to improve the diagnostic capability of white-light. METHODS: A prospective observational study of 50 consecutive patients, with suspicious malignant/premalignant lesions. White-light images were assessed as suspicious for malignancy/negative for malignancy, whereas NBI images were classified based on the IPCL patterns. All lesions underwent biopsy and accuracy was compared with the histopathology (Fig. 1). Fig. 1 Representative images of the IPCL patterns from Types I-IV RESULTS: 25 lesions (49%) were positive for malignancy, 2 (3.9%) lesions showed severe dysplasia, and 24(47%) were considered negative on histopathology. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of white light and NBI in detecting invasive carcinoma was 74.07%, 79.17%, 80.00%, 73.08% and 76.47%, and 92.67%, 90.16%, 92.56%, 91.67% and 92.16% respectively. The NBI group had a significantly better sensitivity and specificity to white light. The interobserver concordance was κ = 0.881. CONCLUSION: NBI is a highly effective tool to detect invasive carcinomas amongst suspicious lesions of the oral cavity.

Indian Council of Medical Research consensus document on hepatocellular carcinoma.

This document aims to assist oncologists in making clinical decisions encountered while managing their patients with hepatocellular carcinoma (HCC), specific to Indian practice, based on consensus among experts. Most patients are staged by Barcelona Clinic Liver Cancer (BCLC) staging system which comprises patient performance status, Child-Pugh status, number and size of nodules, portal vein invasion and metastasis. Patients should receive multidisciplinary care. Surgical resection and transplant forms the mainstay of curative treatment. Ablative techniques are used for small tumours (<3 cm) in patients who are not candidates for surgical resection (Child B and C). Patients with advanced (HCC should be assessed on an individual basis to determine whether targeted therapy, interventional radiology procedures or best supportive care should be provided. In advanced HCC, immunotherapy, newer targeted therapies and modern radiation therapy have shown promising results. Patients should be offered regular surveillance after completion of curative resection or treatment of advanced disease.

Clinico-pathological correlates and survival outcomes in 214 resected ampullary adenocarcinomas - are outcomes different in intestinal and pancreatobiliary subtypes with adjuvant gemcitabine?

BACKGROUND: Evidence suggests that intestinal type (IT) and pancreatobiliary (PB) subtypes of ampullary adenocarcinoma (AC) may have different outcomes. The current study evaluated differences in outcomes between these subtypes and the benefit of adjuvant chemotherapy (AT). METHODS: A prospectively maintained database of patients who underwent upfront resection for AC from January 2012 to March 2016 was conducted. A dedicated pathologist reported differentiation between IT and PB subtypes. RESULTS: 214 patients were included for analysis: 105 PB subtype and 109 IT subtype. With a median follow up of 46.3 months, estimated 4 year overall survival (OS) was 65.8%. In patients with stage II-III disease, lymph-node ratio (LNR) < 0.2 [Not reached (NR) vs. 30.72 months; p = 0.002], absence of perineural invasion (PNI) (NR vs. 31.61 months; p = 0.032) and AT (gemcitabine - 96.1%) (NR vs. 22.28 months) were prognostic for superior OS. There was no difference in OS between IT and PB subtypes, but both subtypes with stage II-III disease benefitted from AT statistically as compared to observation (IT: NR vs. 28.62 months; PB: 18.46 months vs. 58.09 months; p < 0.001). CONCLUSIONS: AC-IT and AC-PB did not have a different OS when treated with resection and adjuvant gemcitabine, though adjuvant therapy benefitted both subtypes individually.

Intraoperative frozen section for detection of occult metastasis in clinically N0 neck does not improve outcome in oral cavity carcinomas.

OBJECTIVE: The objective of this study was to evaluate the utility of frozen section (FS) in detecting occult nodal metastasis in cN0 OSCC and its impact on regional failure and survival. MATERIALS AND METHODS: Clinical records of patients of OSCC operated from January 2013 to December 2014 were retrospectively reviewed. These patients were divided into two groups-Group A comprised of patients who underwent selective neck dissection (SND) (level III/IV) and FS based completion (level IV ± V); Group B included patients who underwent SND I-III/IV without FS. The sensitivity and specificity of FS in detecting occult metastasis was calculated. The regional failure rates and overall survival (OS) between the two groups were compared. RESULTS: The sensitivity, specificity, PPV (positive predictive value) and NPV (negative predictive value) of FS in detecting occult metastasis were 64.06%, 100%, 100%, and 92.15%, respectively. There was no significant difference in regional failure rates (p = 0.219) and OS (p = 0.08) between the two groups. CONCLUSION: FS has a poor sensitivity in detecting occult nodal metastasis. FS-guided neck dissection does not have a significant impact in reducing regional failure or improving OS in clinically node-negative neck in oral cavity carcinomas.

Neoadjuvant Chemoradiation Followed by Surgery for Locally Advanced Gallbladder Cancers: A New Paradigm.

PURPOSE: Locally advanced (T3/T4) gallbladder cancers with large fixed portal nodes have a dismal prognosis. If undertaken, surgery entails extensive resections with high morbidity; therefore, in many centers, patients are offered palliative chemotherapy. In this prospective study, we used neoadjuvant concurrent chemoradiation with the intention of downstaging and facilitating R0 resection of these tumors. PATIENTS AND METHODS: Twenty-eight patients with locally advanced carcinoma gallbladder (stage III, having deep liver infiltrations and/or large portal nodes) underwent prior positron emission tomography/computed tomography to rule out metastatic disease. All were treated with concomitant chemoradiation using helical tomotherapy (dose of 57 Gy over 25 fractions to the gross tumor and 45 Gy over 25 fractions to the surrounding nodes) with injectable gemcitabine (300 mg/m(2)/week × 5 weeks). RESULTS: Of the 28 patients, 25 (89 %) successfully completed planned chemoradiation and 20 (71 %) achieved partial or complete radiologic response. Eighteen (64 %) patients were surgically explored, of whom 14 (56 %) achieved R0 resection. At the median follow-up of 37 months for the surviving patients, the median overall survival (OS) was 20 months for all patients. Only one patient recurred in the common bile duct postsurgery, whereas six patients had distant metastasis. The 5-year OS was 24 % for all patients and 47 % for patients with R0 resection. Biliary leak was seen in 6 (43 %) patients, of whom two required interventions. CONCLUSION: Locally advanced unresectable cancers may benefit from neoadjuvant chemoradiation to facilitate a curative resection with a good survival.

Unexpected benign histopathology after pancreatoduodenectomy for presumed malignancy: accepting the inevitable.

BACKGROUND: Differentiating malignant and benign disease in the pancreatic head and periampullary region is difficult. The aim of this retrospective study was to analyze patients with unexpected "benign" disease after pancreatoduodenectomy (PD) to evaluate the incidence, possible discriminating factors, and outcome. The role of preoperative pathology interpretation in diagnosing malignancy was also assessed. METHODS: Patients with unexpected benign disease were identified from a prospectively maintained database of 446 PDs for presumed malignancy from April 2006 to December 2013. Clinical, radiological, and pathological features were reviewed. Positive predictive values (PPVs) of preoperative pathology interpretation were analyzed. Short-term outcomes were compared. RESULTS: Incidence of unexpected benign disease was 6.5 % (29/446). Radiological diagnostic signs (except the double duct sign) suggestive of malignancy were seen in more than half of the benign cases. Preoperative pathology 'positive' or 'suspicious for malignancy' had a PPV of 97.6 % and 'indeterminate disease' and had a PPV of 90 % for malignancy. 'Benign' or 'negative' pathology had a PPV of 19 % for benign disease in strongly suspected malignancy. There was no significant difference in outcomes in PD for benign versus malignant disease except for a decreased rate of POPFs and a higher trend toward mortality. However, both outcomes were not independently associated with benign disease. CONCLUSIONS: A small percentage of benign disease after PD for "strongly suspected malignancy" is inevitable. No radiological or pathological features can reliably discriminate benign from malignant in these patients. Trend toward higher mortality after PD for unexpected benign disease exists. Detailed preoperative pathological subclassifications are helpful in malignancy.

Role of intraoperative frozen section for assessing distal resection margin after anterior resection.

BACKGROUND AND AIMS: The use of neoadjuvant long-course chemoradiotherapy (LCRT), shorter distal safety margins (DSMs) and stapled or intersphincteric resections has increased sphincter preservation rates. While intraoperative frozen section (IOFS) is not mandatory, it helps achieve negative distal resection margins (DRMs). Our aim was to audit the role of IOFS for DRM assessment while performing sphincter-saving rectal surgery and to identify those subgroups that would benefit the most from IOFS analysis. METHODS: Patients who underwent rectal cancer surgery between 2009 and 2013 were identified from a prospectively maintained database. Patients who intraoperatively underwent an IOFS for DRM assessment were included in the study. Factors associated with a positive margin on IOFS were analysed. The sensitivity and specificity of IOFS were also assessed. RESULTS: Of 250 patients, who had an anterior resection with an IOFS, 12 had an involved DRM. Of these patients, eight were involved by adenocarcinoma, two by acellular mucin, one by moderate dysplasia and one by adenoma confirmed on paraffin section. Positive margins had a 100 % intervention rate. There were two false negative on IOFS. IOFS had a sensitivity of 85.17 % with a specificity of 100 % and a negative predictive value of 99.16 %. Specimens with a positive IOFS were lower rectal (P < 0.05), poorly differentiated and post LCRT locally advanced tumours. CONCLUSIONS: IOFS to confirm negative DRM is recommended in lower rectal tumours irrespective of DSM. It can be considered for locally advanced post LCRT poorly differentiated mid rectal tumours and avoided for upper rectal tumours.

Primary Pancreatic GIST - A-Single Centre Case Series and Systematic Review of Literature.

PURPOSE: GISTs arising from organs outside GI tract are defined as extragastrointestinal GISTs (EGIST). The majority of EGISTs arise from small intestinal mesentry, mesocolon, omentum, retroperitoneum, abdominal wall, liver and pancreas with pancreas comprising less than 5% of it. Due to limited data, it is unknown if the results of GIST can be generalised for EGISTs. We thereby present the largest single-centre case series of primary pancreatic GIST so far with review of existing literature. METHODS: A total of 9 patients of primary pancreatic GIST were treated at our institute from September 2016 to February 2023. After literature search for all studies published before February 2023, 51 articles including 57 patients were identified. Their clinicopathological data and survival analysis were assessed. RESULTS: The median age of patients treated at our centre was 53 years with a female predominance. The most common epicentre was pancreatic head with abdominal pain as the most common presenting symptom. All 57 patients documented in literature belonged to a similar age group with similar gender predilection. The factors impacting DFS were histologic type, mitotic index, NIH risk category and adjuvant therapy. The median DFS was 74 months with a 5-year DFS being 71.9%, while the 5-year OS was 90.4%. CONCLUSION: Pancreatic GIST is a rare entity. Due to limited evidence and evolving literature, results cannot be generalised to a larger population. Larger case series with longer follow-up data are required to further understand the disease biology and long-term outcomes of pancreatic GIST.

Spindle Cell Lipoma and Pleomorphic Lipoma in the Head and Neck: A Comprehensive Study of Six Cases With Review of Literature.

BACKGROUND: Spindle cell lipomas (SL) and pleomorphic lipomas (PL) are rare variants of lipomas, occurring predominantly in the head and neck region. Laryngeal SL/PL is very uncommon and causes obstructive symptoms needing immediate intervention. These tumors are often challenging in radiology due to the admixture of elements and the presence of adipose tissue may help in diagnosis. From a surgeon's perspective, understanding the nuances of SL/PL is paramount. Histology is the gold standard for diagnosis; however, it often causes diagnostic challenges in biopsy.  Method: A retrospective review of the clinical and pathologic features of archival cases of SL/PL was performed. RESULTS: A total of six cases of head and neck region SL/PL were identified. The age of patients ranged from 21 to 58 years and the male-to-female ratio was 5:1. The tumors were distributed in the nape of the neck (n=3), laryngeal region (n=2), and orbit (n=1). Histology in all the cases showed a low-grade neoplasm composed of a variable amount of spindle cells and adipose tissue. The stroma was myxoid in most cases. CD34 was diffusely positive in all the cases. CONCLUSION: SLs are a rare and uncommon variant of lipoma with a predilection in the head and neck region. They are low-grade neoplasms with a propensity to recur after years. Having knowledge of this tumor can improve surgical outcomes and better patient care.

Evaluation of an Objective MRI-Based Tumor Regression Grade (mrTRG) Score and a Subjective Likert Score for Assessing Treatment Response in Locally Advanced Rectal Cancers-A Retrospective Study.

Purpose: Magnetic resonance imaging (MRI) with the help of MRI-based tumor regression grade (mrTRG) score has been used as a tool to predict pathological tumor regression grade (pTRG) in patients of rectal cancer post-neoadjuvant chemoradiation. Our study aims to evaluate the ability of MRI in assessing treatment response comparing an objective mrTRG score and a subjective Likert score, with a focus on the ability to predict pathologic complete response (pCR). Methods: Post-treatment MRI studies were retrospectively reviewed for 170 consecutive cases of histopathologically proven rectal cancer after receiving neoadjuvant chemoradiation and prior to surgery by two oncoradiologists blinded to the eventual postoperative histopathology findings. An objective (mrTRG) and a subjective Likert score were assigned to all the cases. Receiver operating characteristic curves were constructed to determine the ability of Likert scale and mrTRG to predict pCR, with postoperative histopathology being the gold standard. The optimal cutoff points on the scale of 1 to 5 were obtained for mrTRG and Likert scale with the greatest sum of sensitivity and specificity using the Youden Index. Results: The most accurate cutoff point for the mrTRG to predict complete response was 2.5 (using Youden index), with a sensitivity of 69.2%, specificity of 69.6%, positive predictive value (PPV) of 85.6%, negative predictive value (NPV) of 46.4%, and accuracy of 69.3%. The most accurate cutoff for the Likert scale to predict complete response was 3.5, with a sensitivity of 47.5%, specificity of 89.1%, PPV of 91.9%, NPV of 39.4%, and accuracy of 59%. mrTRG had a lower cutoff and was more accurate in predicting pCR compared to Likert score. Conclusion: An objective mrTRG was more accurate than a subjective Likert scale to predict complete response in our study.

RET Alterations Differentiate Molecular Profile of Medullary Thyroid Cancer.

PURPOSE: Medullary thyroid cancer (MTC) is a rare cancer originating from parafollicular C cells of the thyroid gland. Therapeutically relevant alterations in MTC are predominantly reported in RET oncogene, and lower-frequency alterations are reported in KRAS and BRAF. Nevertheless, there is an unmet need existing to analyze the MTC in the Indian cohort by using in-depth sequencing techniques that go beyond the identification of known therapeutic biomarkers. MATERIALS AND METHODS: Here, we characterize MTC using integrative whole-exome and whole-transcriptome sequencing of 32 MTC tissue samples. We performed clinically relevant variant analysis, molecular pathway analysis, tumor immune-microenvironment analysis, and structural characterization of RET novel mutation. RESULTS: Mutational landscape analysis shows expected RET mutations in 50% of the cases. Furthermore, we observed mutations in known cancer genes like KRAS, HRAS, SF3B1, and BRAF to be altered only in the RET-negative cohort. Pathway analysis showed differential enrichment of mutations in transcriptional deregulation genes in the RET-negative cohort. Furthermore, we observed novel RET kinase domain mutation Y900S showing affinity to RET inhibitors accessed via molecular docking and molecular dynamics simulation. CONCLUSION: Altogether, this study provides a detailed genomic characterization of patients with MTC of Indian origin, highlighting the possible utility of targeted therapies in this disease.

NIPBL::NACC1 Fusion Hepatic Carcinoma.

Several reports describing a rare primary liver tumor with histologic features reminiscent of follicular thyroid neoplasms have been published under a variety of descriptive terms including thyroid-like, solid tubulocystic, and cholangioblastic cholangiocarcinoma. Although these tumors are considered to represent histologic variants, they lack classic features of cholangiocarcinoma and have unique characteristics, namely immunoreactivity for inhibin and NIPBL::NACC1 fusions. The purpose of this study is to present clinicopathologic and molecular data for a large series of these tumors to better understand their pathogenesis. We identified 11 hepatic tumors with these features. Immunohistochemical and NACC1 and NIPBL fluorescence in situ hybridization assays were performed on all cases. Four cases had available material for whole-genome sequencing (WGS) analysis. Most patients were adult women (mean age: 42 y) who presented with abdominal pain and large hepatic masses (mean size: 14 cm). Ten patients had no known liver disease. Of the patients with follow-up information, 3/9 (33%) pursued aggressive behavior. All tumors were composed of bland cuboidal cells with follicular and solid/trabecular growth patterns in various combinations, were immunoreactive for inhibin, showed albumin mRNA by in situ hybridization, and harbored the NIPBL::NACC1 fusion by fluorescence in situ hybridization. WGS corroborated the presence of the fusion in all 4 tested cases, high tumor mutational burden in 2 cases, and over 30 structural variants per case in 3 sequenced tumors. The cases lacked mutations typical of conventional intrahepatic cholangiocarcinoma. In this report, we describe the largest series of primary inhibin-positive hepatic neoplasms harboring a NIPBL::NACC1 fusion and the first WGS analysis of these tumors. We propose to name this neoplasm NIPBL:NACC1 fusion hepatic carcinoma.

Top 10 Histological Mimics of Neuroendocrine Carcinoma You Should Not Miss in the Head and Neck.

BACKGROUND: The spectrum of neuroendocrine neoplasia (NEN) of the head and neck region is wide-ranging and diverse, including a variety of diagnoses stretching from benign and low-malignant tumor forms to highly proliferative, poor prognosis neuroendocrine carcinoma (NEC). Moreover, there are several non-neuroendocrine differential diagnoses to keep in mind as well, displaying various degree of morphological and/or immunohistochemical overlap with bona fide neuroendocrine lesions. METHODS: Review. RESULTS: While the growth patterns may vary, well-differentiated NEN usually display a stippled "salt and pepper" chromatin, a granular cytoplasm, and unequivocal expression of neuroendocrine markers such as chromogranin A and synaptophysin. However, these features are often less pronounced in NEC, which may cause diagnostic confusion-not the least since several non-NEC head and neck tumors may exhibit morphological similarities and focal neuroendocrine differentiation. CONCLUSION: As patients with NEC may require specific adjuvant treatment and follow-up, knowledge regarding differential diagnoses and potential pitfalls is therefore clinically relevant. In this review, the top ten morphological and/or immunohistochemical mimics of NEC are detailed in terms of histology, immunohistochemistry, and molecular genetics.

A Rare Case of A Low-Grade Inflammatory Leiomyosarcoma/Histiocyte-Rich Rhabdomyoblastic Tumor in the Neck of An Adolescent Male.

Inflammatory leiomyosarcoma (LMS) is a newly included rare tumor entity in the group of smooth muscle tumors in the recent WHO classification. Recent studies have shown skeletal muscle expression within this tumor and its proximity with histiocyte-rich rhabdomyoblastic tumor (HRRT). A 17-year-old male presented with a soft tissue lump over the back of his neck of one-year duration. Radiologically, a lesion measuring 5.9 cm in the largest dimension was seen, extending from the skull base up to the C2 vertebral level, abutting the occipital bone. The initial biopsy was reported as a fibrohistiocytic tumor at the referring laboratory. A microscopic review of the sections from the initial biopsy and subsequent resection revealed a well-circumscribed, cellular tumor composed of plump spindle and polygonal-shaped tumor cells with relatively bland nuclei, moderate to abundant eosinophilic cytoplasm and numerous interspersed histiocytes, including foam cells and lymphocytes. Immunohistochemically, the tumor cells were positive for desmin, MYOD1 and SMA, focally positive for myogenin, while negative for h-caldesmon, SOX10 and S100P. A diagnosis of inflammatory leiomyosarcoma/HRRT was offered. Subsequently, the tumor was tested for MYOD1 (L122R) mutation and was found to be negative. The patient underwent adjuvant radiation therapy and is free-of-disease at 12 months post-treatment. This case constitutes an extremely rare case of an inflammatory LMS/HRRT, identified in the neck region. This tumor should be differentiated from its close mimics, such as a spindle cell/sclerosing rhabdomyosarcoma, as the latter is treated more aggressively, including with chemotherapy, given its relatively poor prognosis.

Assessing the Agreement Between Preoperative Fine-Needle Aspiration Cytology (FNAC) Done for Major Salivary Gland Neoplasm When Reported by Head and Neck Pathologists and Non-head and Neck Pathologists with Its Final Histopathology.

The preoperative FNA is an important investigation in the workup of a salivary gland pathology. A preoperative diagnosis is important to plan management and counsel patients accordingly. In this study, we aimed to assess the agreement between the preoperative FNA and the final histopathology report when reported by a head and neck and a non-head and neck pathologist. All patients with major salivary gland neoplasm having undergone a preoperative FNA before surgery from January 2012 to December 2019 at our hospital were included in the study. Analysis was done to check for concordance between head and neck and non-head and neck pathologists of the preoperative FNA and final histopathology. Three hundred and twenty-five patients were included in the study. The preoperative FNA could identify the tumour as benign or malignant in the majority (n = 228, 70.1%). The agreement between the preoperative FNA, frozen section diagnosis and the reporting of grade in the frozen section and the final HPR was slightly better with the head and neck pathologist (kappa = 0.429, kappa = 0.698 and kappa = 0.257), respectively, than with the non-head and neck pathologist (kappa = 0.387, kappa = 0.519 and kappa = 0.158), all of which was statistically significant (p < 0.001). The diagnosis made with the preoperative FNA and reporting in the frozen section had a fair agreement with the final histopathology when reported by a head and neck pathologist in comparison to a non-head and neck pathologist.

Nonsalivary Primary Adenocarcinomas of the Base of the Tongue: A Single Tertiary-Care Oncology Center Series of 6 Cases.

CONTEXT.­: Nonsalivary primary adenocarcinomas of the base of the tongue (PABOTs) are extremely rare and worth reporting. OBJECTIVE.­: To study the detailed clinicopathologic features of PABOT. DESIGN.­: Cases of PABOT diagnosed on pathology material were retrieved from the archived electronic surgical pathology records. RESULTS.­: Six cases in 4 men and 2 women (M:F ratio, 2:1), with an age range of 31 to 76 years, satisfied the criteria. The tumor epicenter was the base of the tongue in all (6 of 6; 100%), with extension to the epiglottis in 50% (3 of 6), nodal metastasis in 66.7% (4 of 6), and distant metastasis in 33.3% (2 of 6). On histology, all but one were pure adenocarcinoma. Five of 6 cases (83.3%) had a gastrointestinal (GI) phenotype, of which 2 (40%) had a colonic/lower-GI-type (small groups of cells floating in mucin, CK20+, SATB2+, and CDX2+) and 3 (60%) had an upper-GI-like adenocarcinoma (UGI-LA; malignant glands with intracellular mucin, CK7+) histology. Cystic structure suggestive of teratomatous origin was identified in 2 of 5 cases (40%), both with UGI-LA phenotype. The non-GI-type case had a unique histology with squamous differentiation in addition to adenocarcinoma areas, diffuse nuclear ß-catenin on immunohistochemistry, and a corresponding exon 3 CTNNB1 mutation. One patient succumbed to disease, and 4 are alive with disease (follow-up of 1-9 months after completion of therapy). CONCLUSIONS.­: We suggest using the broad term primary adenocarcinomas of the base of tongue (PABOTs), which can be further subdivided into colonic-type adenocarcinoma of the tongue and oral cavity, UGI-LA, and not otherwise specified categories, and reiterate a need for recognition and distinction of PABOT from salivary gland tumors. A subset originates from teratoid/duplication cysts, necessitating extensive sampling. Multicentric studies are essential to clinically and biologically prognosticate each of these categories.