Head & Neck Pathology最新文献

Background and purpose: Described in 2013, intraneural pseudoperineuriomatous proliferations (IPP) present perineurial cells concentrically surrounding the axon-Schwann cell complexes, forming pseudo-onion bulbs. Different from intraneural perineuriomas, rare neoplasms with differentiation of perineural cells, IPP are reactive, associated with fibrosis, and frequently diagnosed histologically as traumatic neuroma (TN). The aim of this study was to characterize IPP by exploring its clinicopathological features and differentiating it from the main neural lesions that are part of the histopathological differential diagnosis through a retrospective study in six Brazilian Oral Pathology laboratories.

Methods: Cases diagnosed as IPP, TN and intraneural perineuriomas were selected from the archives of the participating centers. Data on age, sex, race, symptoms, site, size, and clinical features and diagnosis were obtained from histopathological reports. Hematoxylin and eosin-stained slides were then re-evaluated by two examiners. Finally, statistical tests were performed to assess the association between clinical, pathological and demographic characteristics (p < 0.05).

Results: After reclassification, 152 TN, 48 IPP and no case of intraneural perineurioma were diagnosed. Clinically, IPP and TN are similar, but IPP affects younger individuals, presents less reported pain, and is more commonly found on the tongue, while TN is frequently observed on the lip, alveolar ridge, and mental foramen. Both lesions typically present as fibrous nodules, often clinically misdiagnosed as fibrous hyperplasia. IPP is fibrous in all cases, more superficial in the mucosa, less frequently associated with adipose tissue and inflammation. These features may assist clinical dentists and pathologists in differentiating lesions.

Conclusion: Although histologically similar, pathologists should note the perineural cell proliferation in IPP to avoid confusion with TN (a common reactive lesion) or intraneural perineurioma (a rare neoplastic lesion).

Background: Langerhans cell histiocytosis (LCH) rarely presents in the oral and maxillofacial region, and while isolated and small collections of Langerhans-type cells have been found in periapical cysts, there have been no reported cases of LCH arising in periapical cysts.

Methods: A 58-year-old female presented with isolated erythematous dry skin lesions and a radiolucent lesion of the anterior maxilla. Microscopic examination of the enucleation specimen revealed a periapical cyst with large collections of atypical cells with grooved folded nuclei with eosinophils consistent with LCH. Immunohistochemistry (IHC) was performed to confirm the diagnosis. BRAF mutation status was evaluated with the BRAF p. V600E antibody and the automated real-time PCR-based Idylla™ assay, capable of qualitative detection of 5 mutations in codon 600 of the BRAF gene.

Results: The LCH cells were positive for S100, CD1a, and Langerin (CD 207) and negative for BRAF p. V600E mutations. Ki-67 was 45%.

Conclusion: The association of LCH with a periapical cyst could be explained by the active surveillance and migration of neoplastic Langerhans-type cells in blood to the site of apical chronic inflammation, in a patient with LCH. Careful attention to morphologic features in conjunction with Langerin IHC, helps exclude other closely-related dendritic tumours. BRAF p. V600E testing, ideally with real-time PCR assays, can help identify patients who may benefit from BRAF inhibitor therapies. New generations of sequencing that cover a large panel of genetic alterations beyond the frequent BRAF p. V600E mutations (e.g. rare in-frame BRAF deletions), could provide valuable information about the extent, prognosis and treatment of LCH patients.

Sinus content specimens from patients with chronic rhinosinusitis (CRS) are commonly encountered by surgical pathologists across various practice settings. The inflammatory cellular component of CRS often includes eosinophil-rich inflammation, and the specimens frequently contain polyps. Moreover, noninvasive forms of fungal rhinosinusitis can also be identified in the sinus contents of patients with CRS. This article provides a succinct review of the histopathology of CRS and sinonasal inflammatory polyps.

Background: Over the past two decades, an increased understanding of molecular alterations has greatly refined salivary gland tumor classification. Many tumors that were previously difficult or impossible to classify have been recognized to represent emerging entities based on shared histologic, immunophenotypic and molecular characteristics. While initial attention was given to carcinomas, more recently molecular discoveries have shed light on salivary gland adenomas as well. We present a series of biphasic salivary gland tumors characterized by striking bizarre myoepithelial atypia, unified at the genetic level by evidence of 12q amplification.

Methods: Salivary gland tumors demonstrating bizarre but degenerative-appearing atypia were identified. Immunohistochemistry, MDM2 and HMGA2 fluorescence in situ hybridization (FISH), and/or targeted next-generation sequencing (NGS) were attempted on the cases.

Results: Seven cases were identified. The tumors arose in the parotid gland (3 of 7), oral cavity (3 of 7) and submandibular gland (1 of 7). The patients were 5 women and 2 men, ranging from 53 to 83 years (mean, 65.7 years). Histologically, the tumors appeared well-circumscribed and partially encapsulated. They were highly cellular and solid, with no chondromyxoid stromal component. The tumors were biphasic, with a population of eosinophilic ducts in a background of basaloid cells with variable clear cell change and spindling. The most striking feature in all cases was the presence of scattered cells with bizarrely atypical nuclei with smudgy chromatin. These bizarre cells maintained low nuclear:cytoplasmic ratios and lacked mitotic activity. The biphasic nature of the tumors was demonstrated by the basaloid cells staining with S100, p63 and p40, while the ducts were positive for CD117 and AE1/AE3 (strong). The bizarre cells had a myoepithelial immunophenotype. The Ki67 index ranged from 1 to 10%, with most of the markedly atypical cells not labeling. DNA NGS was successful in 4 cases, demonstrating 12q copy number increase and 5q copy number loss in all 4 cases. RNA sequencing was able to identify increased MDM2 and HMGA2 expression in one additional case, while amplification of MDM2 and/or HMGA2 was also demonstrated in 6 of 7 cases by FISH. In summary, all 7 cases exhibited evidence of 12q amplification by at least one technique.

Conclusion: Salivary gland neoplasms with bizarre myoepithelial atypia are consistently associated with evidence of 12q amplification. Although this histologic alteration may be alarming, the smudgy nature of the chromatin and paucity of mitotic activity and Ki67 labeling suggest that this finding may not necessarily be indicative of malignancy.

Case presentation: A 30-year-old man presented with a multilobulated left parotid mass measuring 5.2 × 4.1 × 2.4 cm by imaging, and numerous enlarged left cervical lymph nodes, suspicious for metastasis. FNA cytopathology of the mass showed loose clusters of large cells displaying increased N/C ratios and ample granular oncocytic cytoplasm. A superficial left parotidectomy with radical resection of the cheek and cervical lymphadenectomy was performed. Histopathologic examination disclosed a circumscribed, unencapsulated neoplasm exhibiting a solid growth pattern composed of infiltrative islands and nests of cohesive, polygonal, oncocytoid cells in a densely fibrous stroma. Lesional cells exhibited enlarged, oval, open-face nuclei with coarse chromatin and a single acidophilic macronucleolus, voluminous eosinophilic granular cytoplasm and distinct cell membrane borders. Mitotic activity and necrosis were absent. Microcystic architecture was noted solely in a single tumor nest at the periphery. These spaces contained mucinous secretions and were lined by cuboidal oncocytic and intermediate cells with interspersed mucocytes, highlighted by mucicarmine stain. Immunohistochemically, oncocytic cells were strongly and diffusely positive for cytokeratin AE1/AE3, p63 and p40, and uniformly negative for androgen receptor, GATA3, S100, SOX10 and Her-2. A MAML2 rearrangement was identified by FISH, thus confirming the diagnosis of oncocytic variant of mucoepidermoid carcinoma.

Conclusion: In this illustrative example, we present the clinicoradiologic, cytologic, histopathologic, and immunophenotypic characteristics of this rare variant of mucoepidermoid carcinoma, together with molecular documentation.

Coccidioidomycosis is a rare fungal infection that can closely mimic squamous cell carcinoma (SCC) clinically and radiologically when presenting in the larynx, leading to potential misdiagnosis. This case highlights the importance of considering fungal infections in the differential diagnosis of laryngeal lesions, particularly in endemic regions.

Background: Histiocytoses, including Langerhans cell histiocytosis (LCH), comprise a diverse group of histiocytic disorders characterized by the abnormal accumulation and proliferation of histiocytes in various tissues or organs throughout the body, ranging from benign, self-limited conditions to aggressive malignancies and systemic inflammatory syndromes. These lesions present unique diagnostic challenges due to their broad spectrum of clinical presentations, overlapping histopathological and immunophenotypical features, and genetic complexity.

Methods: This review analyzes major histiocytic lesions, focusing on their epidemiology, clinical presentations, histologic and immunophenotypic features, and genetic characteristics to facilitate accurate diagnosis and differentiation among these histiocytoses.

Results: LCH, a well-recognized lesion, can affect various organ systems and necessitates differentiation from other types of histiocytoses such as Erdheim-Chester disease (ECD), Rosai-Dorfman-Destombes disease (RDD), and cutaneous and mucocutaneous non-Langerhans cell histiocytoses. Some histiocytic lesions, such as histiocytic sarcoma, are inherently malignant, while others, like hemophagocytic lymphohistiocytosis (HLH), manifest as severe, potentially life-threatening systemic inflammatory syndromes. Recent molecular genetic studies revealed recurrent genetic alterations in the MAPK pathway, such as BRAF V600E and MAP2K1 in LCH and ECD, and KRAS, NRAS, and MAP2K1 mutations in a subset of RDD. Malignant histiocytoses frequently show alterations in tumor suppressor genes like TP53 and CDKN2A.

Conclusion: Precise classification of histiocytic lesions relies on a comprehensive diagnostic approach that integrates clinical, histologic, immunophenotypic, and genetic data. Recent genetic advances shed light on these conditions' unique but occasionally overlapping pathogenic mechanisms. Molecular genetics advancements continue to refine diagnostic accuracy and present new therapeutic targets, especially for aggressive or treatment-resistant cases.

Background: Dermatologic lesions with notable eosinophilic infiltration of the head and neck region represent a diverse group of conditions, ranging from benign to malignant proliferations.

Methods: We performed a comprehensive literature review focusing on head and neck dermatologic conditions that commonly present with a prominent eosinophilic infiltrate.

Results: This review provides an overview of common entities showing prominent associated eosinophilic inflammatory infiltrates in this region, including epithelioid hemangioma, eosinophilic cellulitis (Wells syndrome), eosinophilic folliculitis, eosinophilic granulomatosis with polyangiitis (Churg-Strauss syndrome), granuloma faciale, and Langerhans cell histiocytosis (LCH).

Conclusion: Eosinophils play a key role in the pathogenesis of these disorders, although the exact mechanisms remain poorly understood. Accurate diagnosis is crucial for differentiating these conditions, as they can share similar histologic features. This review aims to enhance understanding of these eosinophilic dermatologic conditions, improving diagnostic accuracy and treatment strategies.

Tissue eosinophilia is a common finding during histopathologic evaluation and recognizing its presence oftentimes aids pathologists in arriving at the correct diagnosis. The head and neck region is an anatomic location where an abundance of eosinophil-rich disorders occur. In this review, we seek to provide an overview of eosinophil morphology, production, regulation, lifecycle, recruitment, function, and mediators. We will also summarize the most commonly diagnosed eosinophil-rich disorders, both non-neoplastic and neoplastic, occurring in the head and neck.

Purpose: Plasma circulating tumor HPV DNA (ctHPVDNA) persistence after curative-intent treatment may identify patients with HPV-positive cancers at risk for recurrence. Technical validation is required for use as an integral biomarker in a prospective clinical trial.

Methods: Development and analytical validation of a digital droplet PCR assay for detection and quantification of 13 high-risk HPV types (i.e., Cell-Free 13) was performed with oligonucleotides/plasmids encoding type-specific E6/E7 coding regions. Clinical performance, determinants of detection/quantification, and associations of pre-treatment ctHPVDNA with progression-free survival (PFS) were also evaluated in a prospective cohort of 272 head and neck cancer patients.

Results: Limit of detection, limit of quantification, and linear range of quantification were 5, 16 and 16-200,000 virus copies for all 13 high-risk HPV types. No cross-reactivity was detected across all 13 HPV types. At 10,000 copies, inter-assay coefficients of variation ranged from 0.3 to 4.6%. Multiplexing, DNA purification method, input plasma volume, total input cell-free (< 1800 ng) or genomic (< 700 ng) DNA did not affect HPV detection or quantification. The assay had a sensitivity of 91.7% (95%CI 87.3-94.9%) and specificity of 97.7% (95%CI 87.7-99.9%) for ctHPVDNA detection in the setting of newly diagnosed HPV-positive oropharyngeal cancer. Tumor and nodal stage categories, tumor viral load (ρ = 0.41, p < 0.05), and HPV integration status were associated with ctHPVDNA quantitative level. Pre-treatment ctHPVDNA greater than the median (231 copies/ml) was associated with worse PFS (HR = 2.14, 95%CI 1.16-3.97, p = 0.0156) in univariate analysis. However, this was no longer significant after adjustment for clinical covariates (HR_adj = 1.81, 95%CI 0.97-3.37, p = 0.0635).

Conclusion: Cell-Free 13 demonstrated excellent analytical performance and clinical sensitivity/specificity in HPV-positive oropharyngeal cancer. Pre-treatment ctHPVDNA may be associated with oncologic outcomes.