Orbital Sarcoma with BCOR Genetic Alterations in the Pediatric Age Group.

Introduction: Pediatric orbital tumors encompass a wide spectrum of neoplasms, many of which are malignant small round cell tumors with overlapping histology. Sarcomas with BCOR genetic alterations are undifferentiated round cell sarcomas (URCS) characterized by BCOR rearrangements or internal tandem duplications, having distinct clinical features. Being previously unrecognized in the orbit, they have potential for misdiagnosis. Patients: We describe two cases of orbital sarcomas with BCOR genetic alterations. Results: Both girls, 8 and 16 months of age, respectively, presented with progressive proptosis. Both tumors showed sheets of round to ovoid cells with monomorphic nuclei and frequent mitoses. Delicate branching capillaries and myxoid stroma were absent. Diffuse BCOR, cyclin D1, and SATB2 immunopositivity was present. Conclusion: Orbital sarcomas with BCOR genetic alterations are extremely rare. Pathologists should have high index of suspicion for novel genetically defined entities in the differential diagnosis of pediatric orbital URCS and perform appropriate ancillary tests for accurate diagnosis.

GenSelfDiff-HIS: Generative Self-Supervision Using Diffusion for Histopathological Image Segmentation.

Histopathological image segmentation is a laborious and time-intensive task, often requiring analysis from experienced pathologists for accurate examinations. To reduce this burden, supervised machine-learning approaches have been adopted using large-scale annotated datasets for histopathological image analysis. However, in several scenarios, the availability of large-scale annotated data is a bottleneck while training such models. Self-supervised learning (SSL) is an alternative paradigm that provides some respite by constructing models utilizing only the unannotated data which is often abundant. The basic idea of SSL is to train a network to perform one or many pseudo or pretext tasks on unannotated data and use it subsequently as the basis for a variety of downstream tasks. It is seen that the success of SSL depends critically on the considered pretext task. While there have been many efforts in designing pretext tasks for classification problems, there have not been many attempts on SSL for histopathological image segmentation. Motivated by this, we propose an SSL approach for segmenting histopathological images via generative diffusion models. Our method is based on the observation that diffusion models effectively solve an image-to-image translation task akin to a segmentation task. Hence, we propose generative diffusion as the pretext task for histopathological image segmentation. We also utilize a multi-loss function-based fine-tuning for the downstream task. We validate our method using several metrics on two publicly available datasets along with a newly proposed head and neck (HN) cancer dataset containing Hematoxylin and Eosin (H&E) stained images along with annotations.

Shining Light on Rarity: Mucoepidermoid Carcinoma of the Esophagus with Absence of MAML2 Gene Rearrangement.

Primary mucoepidermoid carcinoma of the esophagus is a rare condition characterized by a combination of squamous and mucin-secreting glandular malignant cells. Its clinical recognition is often challenging, pre-operative diagnosis is difficult, and there is a lack of standardized treatment protocols. Here, we present the clinicopathological characteristics of a previously underreported esophageal malignancy found in the distal esophagus of a 58-year-old woman. The initial endoscopic biopsy posed diagnostic challenges due to its small size and inadequate representation of glandular differentiation components making a final diagnosis of poorly differentiated squamous cell carcinoma. Recognizing the resectability of the tumor prompted surgical removal, revealing islands of squamous cells along with intermediate cells and mucin pools. Additionally, MECs in majority of the cases show MAML2 gene rearrangement; contrarily, the present case showed negative results. Enhanced clinicopathological awareness of esophageal MEC facilitated a definitive diagnosis and better patient management. It is imperative to increase awareness and globally document cases of esophageal MEC to enhance understanding, diagnosis, and management guidelines for this malignancy in this anatomical location.

Isolated masseter muscle fungal invasion: unmasking the culprit.

This case report focusses on a unique and infrequently observed event where an isolated masseter muscle fungal invasion was seen. The patient's symptoms include facial swelling and restricted mouth opening. The rarity of this particular manifestation is emphasised by the fact that there are no previously reported cases where fungal infection was the cause of isolated masseter muscle involvement. This lack of documented cases underscores the novelty and significance of the current case.

Association of Epstein-Barr virus (EBV) with nasopharyngeal carcinoma: Experience from a North Indian tertiary care hospital.

INTRODUCTION: Nasopharyngeal carcinoma (NPC), arising from nasopharyngeal epithelium is caused by Epstein-Barr virus (EBV). It is common in South China, South East Asia and North East India. The aim and objectives of this study were to determine the prevalence of EBV in formalin-fixed paraffin-embedded (FFPE) tissue sections of clinically suspected NPC patients, correlate the results of polymerase chain reaction (PCR) with histopathology findings, and to determine the utility of tissue EBV DNA as a diagnostic bio-marker. MATERIALS AND METHODS: 31 FFPE tissue samples were collected from clinically suspected NPC patients from April 2018-December 2019. Histopathological diagnosis was done by examination of Hematoxylin and Eosin stained slides. Presence of EBV was detected by EBNA-1 PCR. IHC was performed using EBV Latent Membrane Protein 1. RESULTS: Of the 31 clinically suspected NPC cases, 15 (48.4 %) were histopathological confirmed NPC. Of these15, 13 (86.6 %) were non-keratinising undifferentiated NPC, and one each were keratinising NPC and non-keratinising differentiated NPC respectively. EBV EBNA1 PCR was positive in 35.5 % (11/31) of clinically suspected NPC cases. Of the 11 PCR positive cases, 9 (81.8 %) were histopathological confirmed NPC. Of the 31 clinically suspected NPC cases, IHC was indicated in 23 biopsies. Of which, 12 (52.2 %) were positive for LMP1 in the abnormal cells. Of the 12 IHC positive samples, 10 were NPC cases. CONCLUSION: EBV DNA as an indicator towards NPC among clinically suspected cases had a sensitivity of 60 % and specificity of 87.5 %. In this study, addition of EBV DNA detection by PCR from FFPE tissue sections could confirm EBV association in 20 % of cases where it was not detected by EBV LMP1 IHC, thus helped in increasing the detection of EBV positivity in NPC cases. Early diagnosis of NPC will improve the cure rate and hence reduce the morbidity and mortality rates.

Superior Parathyroid Masquerading as Retropharyngeal Lymph Node.

Introduction: Ectopic parathyroid glands have been reported with an incidence of 2-22%. Undescended parathyroid glands, defined as glands situated above the carotid bifurcation or > 1 cm cranial to the superior pole of the thyroid gland, comprise 2-7% of all ectopic parathyroid glands. We report a case of incidentally discovered parathyroid gland located in the retropharyngeal space at the level of the oropharynx. Case Presentation: The patient in this report was a 60-year-old female with squamous cell carcinoma of the tonsil T2N0M0 with MRI showing a hyperintense ovoid structure, medial to the carotids at the level of the oropharynx, corresponding to the location of the lateral group of retropharyngeal lymph nodes. Patient underwent transoral ultrasonic radical tonsillectomy along with a retropharyngeal lymph node dissection by the transcervical route. Postoperative histopathology revealed the retropharyngeal node sampled to be a normal parathyroid gland. Discussion: "High" undescended parathyroid gland as reported here along with 4 other cases of infratemporal fossa parathyroid glands reported previously, can be the cause for recurrent missed adenomas. Being extracervical in location, these are likely to be missed if the skull base has not been included in the preoperative Tc-99 sestamibi scan and also during bilateral neck exploration.

Pre-vascular Facial Nodes: Sentinel Station for Metastasis in Gingivobuccal Complex Cancers.

BACKGROUND: Pre-vascular facial nodes (PV-FNs; perifacial lymph nodes) are supra-mandibular lymph nodes above the inferior border of the mandible. These are not part of routine neck dissection done for OCSCC. These lymph nodes can be sentinel station for metastatic lymph nodes from gingivobuccal complex cancers and are missed during routine neck dissection. It is imperative to include this sentinel station in routine neck dissection to prevent nodal recurrences. MATERIALS AND METHODS: One hundred thirty-seven patients with GBCC (T1-T4) were prospectively recruited between May 2020 and June 2022 with the intent to evaluate the incidence of PV-FN metastases and clinicopathological factors predicting them. RESULTS: PV-FN metastases were seen in 26 patients (18.9%; 26/137). The occult metastasis rate was 8.7% (12/137). On multivariate analysis, pathological T4 stage (pT4), LVE positivity, and intermediate-high BGS were statistically significant predictors of PV-FN metastases in our study. CONCLUSIONS: Incidence of PV-FN metastasis is high (18.9%) in GBCC, which can be potentially the first sentinel station in the lymphatic drainage pattern for this sub-site. Meticulous clearance of this nodal basin is of paramount importance during neck dissection to prevent nodal recurrences. LEVEL OF EVIDENCE: Level 2 (CEBM-Level of Evidence-2.1) Laryngoscope, 2024.

Perimarginal quadrangle dissection: Pushing the boundaries of neck dissection in gingivo-buccal complex cancer.

OBJECTIVES: Perimarginal nodes (PMN) lie in close relationship with marginal mandibular nerve (MMN), in the lymphatic drainage pathway of gingivo-buccal cancers (GBC), above the lower border of mandible and remain unaddressed in conventional neck dissection. We have aimed to define the boundaries of perimarginal node dissection, explore incidence of PMN metastasis and its correlation with histopathological characteristics. MATERIALS AND METHODS: A prospective study was conducted on 112 consecutive patients of GB carcinoma. PMN dissection was performed in an anatomically defined quadrangle. Prospective clinical characteristics included subsite, tumor and nodal stage, location of primary and clinical skin involvement. Histopathological characteristics analyzed included grade, size, pathological tumor, nodal stage, skin and/or bone involvement, depth of invasion, Brandwein Gensler histological risk score and lympho-vascular emboli. MMN function was graded at 3 and 6 months post-operatively. RESULTS: The PMN were identified histologically in 75.89 % patients. 15.2 % patients harboured metastasis in PMN. 16.7 % patients had clinically occult metastasis with 11.7 % having isolated PMN metastasis. None of the pre-operative clinical factors was found to be significant in predicting incidence of metastasis. Higher nodal burden (p = 0.01) and pathological skin involvement (p = 0.03) were found statistically significant on multivariable analysis. At 6 months follow-up, none of the patients had any MMN functional deformity at rest. CONCLUSION: There is a high incidence of occult PMN metastasis from gingivo-buccal complex cancer. High nodal stage and pathological skin involvement are independent predictors for PMN metastasis. PMN dissection must be performed in all cases of GB cancer.

A comparative study of smooth muscle cell characteristics and myofibroblasts in processus vaginalis of pediatric inguinal hernia, hydrocele and undescended testis.

BACKGROUND: Congenital inguinal hernia, hydrocele and undescended testis (UDT) are associated with patent processus vaginalis. The smooth muscles present in the processus vaginalis aid in the descent of the testis and undergo programmed cell death after testicular descent leading to obliteration. The persisting amount of smooth muscle in the processus vaginalis influences the clinical outcome as inguinal hernia, hydrocele or UDT. Therefore, a study was conducted to evaluate the processus vaginalis in these three conditions to observe the presence and phenotype of smooth muscle cells and the presence of myofibroblasts. MATERIALS AND METHODS: The processus vaginalis sacs in patients with inguinal hernia, hydrocele and UDT were examined using light microscopy for the presence and distribution of smooth muscle cells and immunohistochemical staining for vimentin, desmin, and α-smooth muscle actin (SMA) to identify the smooth muscle phenotype. Transmission electron microscopy was also performed in all the sacs to observe the presence of myofibroblasts. RESULTS: Seventy-eight specimens of processus vaginalis (from seventy-four patients), distributed as 47%, 27%, and 26% as inguinal hernia, hydrocele and UDT respectively, were included in the study. The sacs from inguinal hernia and hydrocele had significantly more presence of smooth muscles distributed as multiple smooth muscle bundles (p < 0.001). Desmin and SMA staining of smooth muscle cells was observed in significantly more sacs from hydrocele, followed by inguinal hernia and UDT (p < 0.001). The sacs from UDT had a significant presence of striated muscles (p = 0.028). The sacs from inguinal hernia had a significant presence of myofibroblasts, followed by hydrocele and UDT (p < 0.001) and this significantly correlated with the light microscopy and immunohistochemical features. The processus vaginalis sacs from four female patients did not differ statistically from the male inguinal hernia sacs in any of the above parameters. CONCLUSION: The processus vaginalis sacs in pediatric inguinal hernia, hydrocele and undescended testis differ in the presence, distribution and phenotype of smooth muscles and the presence of myofibroblasts. The clinical presentations in these entities reflect these differences.

Frequent Immunohistochemical Expression of Transcriptional Repressor GATA Binding 1 in Salivary Gland Neoplasms: A Sensitive but Nonspecific Marker.

CONTEXT.­: Salivary gland (SG) neoplasms (SGNs) display considerable immunophenotypic diversity. A significant proportion of SG carcinomas develop metastases with increased diagnostic difficulty at metastatic sites. Transcriptional repressor GATA binding 1 (TRPS1), a novel immunohistochemical marker for breast cancer, has been found to stain certain SGNs. OBJECTIVE.­: To investigate TRPS1 and SRY-related HMG-box 10 (SOX10) immunoexpression in various SGNs and non-SG carcinomas, head and neck paragangliomas, and head and neck mucosal melanomas. DESIGN.­: TRPS1 immunoreactivity score (IRS) was determined as negative or low, intermediate, or high positive; SOX10 was reported as negative or positive. RESULTS.­: One hundred forty-eight SGNs, 5 breast carcinomas, 105 nonbreast-non-SG carcinomas, including 33 head and neck squamous cell carcinomas (HNSCCs), 6 head and neck paragangliomas, and 6 head and neck mucosal melanomas, were assessed for TRPS1. All 23 benign SGNs showed TRPS1 positivity, with the majority having high-positive IRS (17 of 23 cases; 74%). Among 125 SG carcinomas, 115 of 125 (92%) were TRPS1 positive, with high-positive IRS in 94 of 125 (75%), intermediate positive in 15 of 125 (12%), and low positive in 6 of 125 (5%). Among nonbreast-non-SG carcinomas, HNSCC, lung, thyroid, kidney, and ovarian carcinomas showed frequent TRPS1 staining. Nearly half of HNSCCs had high (11 of 18; 33%) or intermediate (4 of 18; 12%) positive IRS. Mean IRS in SG carcinomas was significantly higher than that in nonbreast-non-SG carcinomas (P < .001). None of the TRPS1-positive nonbreast-non-SG carcinomas expressed SOX10. CONCLUSIONS.­: TRPS1 is positive in most benign and malignant SGNs. Its expression in several nonbreast-non-SG carcinomas indicates that it lacks specificity for breast and SG carcinomas, even if considering only high-positive IRS. Addition of SOX10 can increase discriminatory utility of TRPS1.

Role of CD34-immunopositive Microvascular Density in Juvenile Nasopharyngeal Angiofibroma.

Objective: To assess the microvascular density (MVD) in juvenile nasopharyngeal angiofibroma (JNA) with CD34 immunostaining and evaluate its relationship with clinico-demographic features. Methods: This prospective study included patients with JNA undergoing endoscopic excision. The histopathological specimen was stained using CD-34 antibodies to calculate MVD. MVD and clinico-demographic features were correlated. Results: The study included 12 patients with a median age of 15.5 years. The mean MVD was 39 vessels/high power field (range 5 to 151 vessels). MVD was significantly associated only with the volume of tumour (r = 0.65, p = 0.02). The recurrence occurred in one patient with an MVD of 107. The median follow-up was 38 months. Conclusion: MVD is significantly associated with tumour volume in JNA, which implies a robust role of angiogenesis in the pathology of the tumour. Also, higher MVD may be a risk factor for recurrence.

Dermoscopy of hypopigmented macules unveiling genetic diagnosis of tuberous sclerosis complex type 2 in an infant presenting with sacral chordoma.

A 2-month-old male with surgically resected sacral chordoma presented with multiple hypopigmented macules showing characteristic patchy, sharply demarcated areas of pigment network on dermoscopy. These dermoscopic findings were suggestive of the ash-leaf macules of tuberous sclerosis over other common hypopigmented macules in neonates. Chordomas presenting in early childhood in the sacral location have been reported as a rare manifestation of tuberous sclerosis complex. The combination of these findings led to a diagnosis of tuberous sclerosis, confirmed with the finding of a heterozygous TSC2 gene deletion; treatment with sirolimus resulted in regression of cardiac rhabdomyomas and hypopigmented macules.

Clinico-pathological Factors in Malignant Transformation of RRP.

Various clinico-pathological factors play role in the papilloma proliferation and pathogenesis of Recurrent respiratory papillomatosis (RRP). However, it is not known if they are directly responsible for malignant transformation of these papillomas or not. We did this study to elucidate any such association. The most recent debrided tissue of RRP in 20 patients was evaluated for p16 expression, VEGF estimation (tissue expression and serum levels), and tissue HPV DNA concentration. The final histopathology results were then correlated with these pathological factors and with clinical factors like duration of illness, age of onset of symptoms, extent of disease, etc. Squamous papilloma was seen in 60%, dysplasia in 25%, and squamous cell carcinoma (SCC) in 15% of the patients. Positive immunostaining for p16 (staining in ≥70% of tumor cells) was seen only in one case, which was SCC. There was no statistically significant difference between p16 expression, tissue VEGF expression, serum VEGF levels, and tissue HPV DNA in any of the histological groups. The mean age of disease onset was significantly higher in patients with SCC (p = 0.03). A significantly higher number of patients with dysplasia had tracheobronchial involvement (p = 0.022). We concluded that no single pathological factor is solely responsible for development of malignancy in RRP, whereas clinical factors like tracheobronchial involvement and age of onset may contribute to development of dysplasia or carcinoma.

Assessment of MUC5AC and MUC2 Immunoexpression in Glandular Odontogenic Cysts, Dentigerous Cysts, and Mucoepidermoid Carcinomas.

Glandular odontogenic cysts (GOCs) and dentigerous cysts may show mucous metaplasia. Central mucoepidermoid carcinoma is very rare and mostly associated with dental cysts. It is hypothesized that odontogenic cysts showing mucus differentiation in their lining, have a propensity to transform into MEC. The present study is the first attempt to explore the relationship between odontogenic cysts [GOCs and dentigerous cysts with mucus metaplasia (DCMM)] and MEC by evaluating immunoexpression of MUC5AC and MUC2. Immunoexpression of MUC5AC and MUC2 was evaluated semiquantitatively in GOCs (20 cases), DCMMs (20 cases), and MECs (20 cases). The percentage of positive cells, intensity, and localization of immunoexpression were assessed for each marker in all cases. Of GOCs, DCMMs, and MECs cases, 85%, 70%, and 80%, respectively, were immunopositive for MUC5AC. Strong cytoplasmic immunoreactivity for MUC5AC was noted, particularly in mucous cells present diffusely within MECs. However, the immunoreactivity was limited to the epithelial lining of GOCs and DCMMs. Most of the MECs (60%) showed more than 25% positivity for MUC5AC, followed by GOCs, and the least in DMMCs. Mild cytoplasmic and nuclear positivity of MUC2 was noted only in epithelial lining cells of 70% GOCs and 45% DCMMs. Whereas, 55% of MECs displayed moderate to strong cytoplasmic and membranous immunopositivity for MUC2 exclusively within mucous cells. As MECs showed strong MUC5AC immunoreactivity in mucous cells, immunoexpression of MUC5AC in odontogenic cysts with mucus cells can possibly explain the pathogenesis of MEC from cysts. However, the variable expression of MUC2 did not give any strong evidence regarding its role as a marker.

Myeloblastic meningeal neoplasm: an unusual natural history.

Myeloid sarcoma is a very rare extramedullary malignant tumour, most often associated with acute myeloid leukaemia. We report the case of a man in his early 20s who presented with chronic headache, raised intracranial pressure and progressive vision loss of 2 years duration with no systemic manifestations. He had a history of myeloid sarcoma of the left thigh 15 years ago, treated with external beam radiotherapy and in complete remission for more than 13 years. However, the progressive blindness remained unexplained for 2 years, and he was eventually diagnosed with isolated meningeal relapse without marrow or systemic involvement. Imaging revealed subarachnoid haemorrhage, diffuse leptomeningeal enhancement and involvement of lower dorsal cord and conus, and cerebrospinal fluid cytology showed myeloid blasts. He was managed with intrathecal chemotherapy and craniospinal irradiation, after which he had mild improvement in vision.

Trichilemmal carcinoma metastatic to parotid gland: First report of fine needle aspiration cytology features.

Trichilemmal carcinoma is a rare malignant cutaneous adnexal neoplasm arising from the outer root sheath of the hair follicle. Majority of cases occur on sun-exposed sites such as the face, scalp and neck, making them easily amenable to being biopsied and subjected to histological examination for definitive diagnosis. Thus, cytological features of trichilemmal carcinoma have not been described till date. Trichilemmal carcinoma is a low-grade malignancy, albeit with potential to metastasize to regional lymph nodes and distant sites. We report the case of trichilemmal carcinoma of scalp that metastasized to cervical lymph nodes and parotid gland and underwent fine-needle aspiration cytology (FNAC) from the parotid lesion. The aspirate showed tightly cohesive cell clusters with sharp borders. Tumour cells ranged from basaloid with scant cytoplasm to those with abundant cytoplasm. Nuclei were vesicular, with inconspicuous to prominent nuclei. Intercellular bridges, masses of keratin, and fragments of desmoplastic stroma were present, closely recapitulating histological features of trichilemmal carcinoma, which enabled diagnosis as metastasis. Cell block showed similar tumour fragments with evidence of differentiation towards outer root sheath. FNAC is the first-line investigation to obtain a tissue diagnosis of masses in the head and neck region. Although rarely encountered, the lack of knowledge of cytological features of trichilemmal carcinoma may hamper its FNAC diagnosis at metastatic sites. When intraparotid metastases occur, they may be mistaken as primary salivary gland carcinoma. Thus, awareness of the cytological features of this tumour must be raised among cytopathologists to enable accurate diagnosis and further management.

Liver Metastasis from Nasopharyngeal Carcinoma Diagnosed on Fine Needle Aspiration Cytology.

A 12-year-old boy presented with abdominal distention for 1 year. On examination, he had massive hepatomegaly. Facial swelling in the maxillary region, palpable left cervical lymph nodes, and a nasal twang to his voice were detected. Imaging showed multiple hypodense liver lesions, necrotic mediastinal and hilar lymph nodes, multiple lytic-sclerotic skeletal lesions, and lesions in the nasopharynx and maxilla. Fine needle aspirate (FNA) from the cervical lymph node yielded blood. FNA from the liver showed singly dispersed and cohesive clusters of tumor cells, with interspersed neutrophils and tingible body macrophages. Cells had scant to moderate fragile cytoplasm, enlarged vesicular nuclei, and prominent nucleoli. Immunohistochemistry on cell block revealed positivity for cytokeratin and Epstein-Barr virus (EBV)-Latent Membrane Protein-1 (LMP1). A diagnosis of metastatic nasopharyngeal carcinoma was made, and was confirmed on a subsequent biopsy from the femur.

Relevance of Partial p16 Immunostaining in Oral Squamous Cell Carcinoma and Co- Relation with HPV DNA Status.

INTRODUCTION: Immunostaining criteria for p16 positivity in oropharyngeal squamous cell carcinoma have been laid down by College of American Pathologists (CAP) and the American Society of Clinical Oncology (ASCO). The staining should be of moderate to strong intensity seen in 70 percent of the tumor cells. Recent studies have pointed out that a small minority of cases are missed using p16 as the surrogate marker at above mentioned cut off. By convention the same criteria have been used for oral squamous cell carcinoma. MATERIAL AND METHODS: The authors revisited the results of their previous study where immunohistochemistry for p16 was found to be positive by AJCC criteria in 139 out of 800 cases of oral squamous cell carcinoma. For this study, all the p16 immunonegative cases (by AJCC criteria) were analysed again for partial staining patterns, defined for this study as cases with 50-75% cells showing 2+/3+ intensity of nuclear p16 immunostaining and for basal predominant pattern of immunostaining. These cases were subjected to HPV DNA PCR. RESULTS: Out of the 661/800 cases found to be negative for p16 immunohistochemistry, a total of 34/800(4.25%) showed partial staining based on the criterion of 50-75% cells showing p16 immunostaining intensity of 2/3+.The basal predominant pattern of immunostaining for p16 was seen in 43/800 (5.38%) cases. When these cases were subjected to HPV DNA analysis, 11/34 (32.35%) of the cases showing partial staining and 02/43 (4.7%) of the cases showing basal predominant pattern of p16 immunostaining were found to be HPV-DNA positive. CONCLUSION: The inclusion of partial immunostaining patterns of p16 in HPV analysis of oral squamous cell carcinoma can improve our understanding of HPV driven oral squamous cell carcinoma.

Role of immunohistochemistry in diagnosing round-cell tumours affecting the oral and maxillofacial regions.

Background: One of the most challenging spectra of lesions in the oral and maxillofacial region (OMFR) are round-cell tumours (RCTs). They show a considerable degree of overlap in microscopy and immunophenotypes. The main aim of this study is to analyse the spectrum of RCTs encountered in the oral and maxillofacial regions. We emphasise the role of immunohistochemistry (IHC) which in conjunction with histological, clinical, and imaging findings is necessary for their correct characterisation. The secondary objectives are to discuss differential diagnosis, workflow, and diagnostic algorithm for round-cell lesions affecting the OMFR. Methods: Formalin-fixed, paraffin-embedded sections of RCTs were retrieved from the archives of the Department of Oral Pathology (January 2018 to March 2020). These cases were analysed by three pathologists independently by evaluating haematoxylin and eosin-stained sections, and immunohistochemical markers employed to characterise these lesions. Results: Under the spectrum of RCTs, 11 cases (0.53%) were diagnosed with a predominance of non-Hodgkin lymphoma (55%) followed by Ewing sarcoma (18%). The remaining were Langerhans cell histiocytosis (9%), neuroendocrine carcinoma (9%), and sinonasal undifferentiated carcinoma (9%). Except for one case, in all cases, the final diagnosis was established with the use of adjunctive IHC. Conclusion: RCTs can pose a diagnostic challenge for inexperienced oral pathologists. Thorough knowledge of the differentials of RCT occurring in oral and maxillofacial is helpful. An algorithm-based diagnostic approach incorporating the clinical, imaging, and histomorphological findings and immunohistochemical evaluation can help in minimizing diagnostic confusion and errors.

Diagnosis of Adenoid Cystic Carcinoma with Striking Tubular Hypereosinophilia by MYB and EWSR1 Breakapart Fluorescence In Situ Hybridization.

BACKGROUND: Adenoid cystic carcinoma (AdCC), associated with MYB/MYBL1 gene rearrangements, shows epithelial and basaloid myoepithelial cells arranged in tubular, cribriform and solid patterns. Variations from this classic morphology make diagnosis challenging, necessitating molecular testing. AdCC with striking tubular hypereosinophilia (AdCC-STE) is one such recently described histological subtype. METHODS: A 52-year-old female presented with a floor of mouth swelling for two months, diagnosed elsewhere as polymorphous adenocarcinoma (PAC). A biopsy was obtained. With a diagnosis of oncocytic neoplasm, wide excision of the tumor was undertaken. Histological examination, fluorescence in situ hybridization (FISH) and ultrastructural examination were performed. Archival cases of PAC and epithelial myoepithelial carcinoma (EMC) were reviewed, and MYB immunostaining and FISH were performed to identify potential AdCC-STE cases. RESULTS: The excised tumor from the index patient showed bilayered tubules, micropapillae and cribriform pattern. Luminal cells with hypereosinophilic to clear cytoplasm were surrounded by flattened abluminal cells. Focally, basophilic matrix was seen within sharply demarcated pseudocystic spaces. FISH revealed MYB and EWSR1 gene rearrangements, confirmatory of AdCC-STE. Electron microscopy showed features consistent with AdCC; however, mitochondria were not prominent. Among 14 archival PACs, two showed MYB immunopositivity; one showed MYB rearrangement but was classical AdCC. Among 35 EMC, one case showed MYB immunoreactivity and eosinophilia of luminal cells but lacked MYB/MYBL1 rearrangement. CONCLUSION: Awareness of unusual histological subtypes of AdCC, such as AdCC-STE, is imperative, as it may be misdiagnosed as PAC and EMC, among others. Presence of basophilic matrix and squamoid morules in a biphasic tumor even with hypereosinophilic rather than basaloid myoepithelial appearance should raise suspicion for AdCC-STE, and prompt molecular testing for confirmation. With wider accessibility, lower cost and significantly shorter turn-around-time when compared to RNA sequencing, FISH can be employed for confirmation of diagnosis, especially in low- and middle-income countries.