The World Health Organization Classification of Head and Neck Tumours recently published the 5th edition. There are new entities, emerging entities, and significant updates to the taxonomy and characterization of tumor and tumor-like lesions, specifically in this article as it relates to nasal cavity, paranasal sinuses and skull base. Importantly, the number of diagnostic entries has been reduced by creating category-specific chapters for soft tissue, hematolymphoid, melanocytic, neuroectodermal, and metastatic tumors. Bone and salivary gland tumors are also not separately reported in the sinonasal tract, but included in the jaw and salivary gland sections, respectively. Repetition of characteristic entities in each anatomic site was also reduced, instead highlighting only the unique features in each anatomic site. Two new entities (SWI/SNF complex-deficient sinonasal carcinomas and HPV-related multiphenotypic sinonasal carcinoma) will be highlighted in this review, with a discussion of several emerging entities. There is a short description of updated information for all 24 diagnostic entities included in this edition to allow the reader a snapshot of current state of knowledge, but to encourage more investigation and further broaden understanding of these diverse and rare entities. 

Update from the 5th Edition of the World Health Organization Classification of Head and Neck Tumors: Nasal Cavity, Paranasal Sinuses and Skull Base

Simple Summary In recent years, there have been several molecular and immunohistochemical additions to the pathologic diagnosis of sinonasal malignancies that could facilitate the identification of clinically relevant groups of sinonasal malignancies. Molecular profiling is progressively integrated in the histopathologic classification of sinonasal carcinomas, and it is likely to influence the management of these tumors in the near future. In this article we review the recent literature on molecular analysis and/or subtyping of sinonasal carcinomas and we discuss the possible clinical implications of a classification of sinonasal tumors based on their molecular features. Abstract Sinonasal carcinomas are a heterogeneous group of rare tumors, often with high-grade and/or undifferentiated morphology and aggressive clinical course. In recent years, with increasing molecular testing, unique sinonasal tumor subsets have been identified based on specific genetic alterations, including protein expression, chromosomal translocations, specific gene mutations, or infection by oncogenic viruses. These include, among others, the identification of a subset of sinonasal carcinomas associated with HPV infection, the identification of a subset of squamous cell carcinomas with EGFR alterations, and of rare variants with chromosomal translocations (DEK::AFF2, ETV6::NTRK and others). The group of sinonasal adenocarcinomas remains very heterogeneous at the molecular level, but some recurrent and potentially targetable genetic alterations have been identified. Finally, poorly differentiated and undifferentiated sinonasal carcinomas have undergone a significant refinement of their subtyping, with the identification of several new novel molecular subgroups, such as NUT carcinoma, IDH mutated sinonasal undifferentiated carcinoma and SWI/SNF deficient sinonasal malignancies. Thus, molecular profiling is progressively integrated in the histopathologic classification of sinonasal carcinomas, and it is likely to influence the management of these tumors in the near future. In this review, we summarize the recent developments in the molecular characterization of sinonasal carcinomas and we discuss how these findings are likely to contribute to the classification of this group of rare tumors, with a focus on the potential new opportunities for treatment.

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Towards a Molecular Classification of Sinonasal Carcinomas: Clinical Implications and Opportunities

“Dedifferentiation” and/or high-grade transformation (HGT) has been described in a variety of salivary gland carcinomas, including acinic cell carcinoma, adenoid cystic carcinoma, epithelial-myoepithelial carcinoma, polymorphous low-grade adenocarcinoma, myoepithelial carcinoma, low-grade mucoepidermoid carcinoma and hyalinizing clear cell carcinoma, although the phenomenon is a rare event. Recent authors tend to preferably use the term HGT instead of “dedifferentiation” in these cases. HGT-tumors are composed of conventional carcinomas juxtaposed with areas of HG morphology, usually either poorly differentiated adenocarcinoma or “undifferentiated” carcinoma, in which the original line of differentiation is no longer evident. The HG component is generally composed of solid nests, sometimes occurring in cribriform pattern of anaplastic cells with large vesicular pleomorphic nuclei, prominent nucleoli and abundant cytoplasm. Frequent mitoses and extensive necrosis is evident. The Ki-67 labeling index is consistently higher in the HG component. p53 abnormalities have been demonstrated in the transformed component in a few examples, but the frequency varies by the histologic type. HER-2/neu overexpression and/or gene amplification is considerably exceptional. The molecular-genetic mechanisms responsible for the pathway of HGT in salivary gland carcinomas largely still remain to be elucidated. Salivary gland carcinomas with HGT have been shown to be more aggressive than conventional carcinomas with a poorer prognosis, accompanied by higher local recurrence rate and propensity for cervical lymph node metastasis, suggesting the need for wider resection and neck dissection.

"Dedifferentiation" and high-grade transformation in salivary gland carcinomas

http://mp.uscap.org/article/S0893395222002708/pdf

Low-grade non-intestinal-type sinonasal adenocarcinoma: a histologically distinctive but molecularly heterogeneous entity

Genomic characterization of a PPP1CB-ALK fusion with fusion gene amplification in a congenital glioblastoma.

Immunohistochemical and genetic analysis of respiratory epithelial adenomatoid hamartomas and seromucinous hamartomas: are they precursor lesions to sinonasal low-grade tubulopapillary adenocarcinomas?

OBJECTIVE Fine-needle aspiration (FNA) is a key diagnostic method in the evaluation of salivary gland lesions. Secondary tumors of salivary glands represent only 5% of all malignancies of major salivary glands. The goal of our study was to examine the cytological and clinical features of secondary tumors sampled by FNA. MATERIALS AND METHODS A series of 36 secondary tumors from the pathology departments of two university hospitals are presented. Clinical referrals to FNA, cytological features, immunohistochemical results, and histopathological diagnoses were reviewed in all cases. RESULTS The study population consisted of 36 cases (19 males and 17 females) with mean age 70.9 ± 13.0 years (range 41-96 years). The most common site of the metastasis was parotid gland (n = 26). The primary malignancy was known in 17 cases at the time of FNA diagnosis. The most common primary site was skin of head and neck area (11 cases) followed by lungs (n = 5) and tonsils (n = 5), kidney (n = 2) and breast (n = 2) and thyroid gland, gastrointestinal tract and soft tissue, 1 case of each. In 8 cases, the primary site remained unknown. The diagnostic or confirmatory immunocytochemistry was performed on cell blocks in 21 cases. CONCLUSIONS FNA is a reliable technique in the diagnosis of salivary gland secondary malignancies. The knowledge of the personal history of malignancy is essential for the successful immunocytochemical targeted diagnosis without any delay.

FNA diagnostics of secondary malignancies in the salivary gland: Bi-institutional experience of 36 cases.

Inflammatory myofibroblastic tumor (IMT) of the uterus is rare but probably underdiagnosed tumor. It is usually benign but small fraction of cases may locally recur or rarely metastasize. Herein, we present a case report of 66-year-old patient with uterine IMT originally diagnosed as leiomyosarcoma of the uterus. The patient died within few months due to local tumor progression with skeletal metastases. Macroscopically, this was a voluminous locally aggressive yellowish-grey tumor of soft consistency limited to myometrium. Microscopically, the tumor was characterized by polymorphic spindle cell proliferation with marked nuclear atypia and numerous mitoses. Small geographic necroses was noticed. Typical histologic features of IMT were represented by lymphocytic infiltrate which was only very small and focal. Myxoid stroma was absent. Immunohistochemically, there was strong and diffuse cytoplasmic positivity of ALK (anaplastic lymphoma kinase). The presence of PPP1CB-ALK fusion transcript was confirmed by molecular-genetic methods. Proper diagnosis of uterine IMT is of importance as there is an option of targeted ALK inhibitor therapy in cases of aggressive tumor behaviour. Currently it is thought that histomorphology of uterine IMT may overlap with that of leiomyosarcoma and STUMP (smooth muscle tumor of uncertain malignant potential). The presence of ALK rearrangement is probably the only reliable diagnostic marker. Thus, ALK immunohistochemistry followed by molecular-genetic testing seems to represent suitable screening tool for the detection of uterine IMT.

Markéta Horáková

Papers

Immunohistochemical and genetic analysis of respiratory epithelial adenomatoid hamartomas and seromucinous hamartomas: are they precursor lesions to sinonasal low-grade tubulopapillary adenocarcinomas?

FNA diagnostics of secondary malignancies in the salivary gland: Bi-institutional experience of 36 cases.

Inflammatory myofibroblastic tumor of the uterus - case report.