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Review
. 2024 Oct 23;14(21):2365.
doi: 10.3390/diagnostics14212365.

Rare Head and Neck Cancers and Pathological Diagnosis Challenges: A Comprehensive Literature Review

Daria Maria Filippini  1   2 , Francesca Carosi  1 , Giulia Querzoli  2   3 , Matteo Fermi  4 , Ilaria Ricciotti  1 , Gabriele Molteni  4 , Livio Presutti  4 , Maria Pia Foschini  5 , Laura Deborah Locati  6   7
Affiliations
Review

Rare Head and Neck Cancers and Pathological Diagnosis Challenges: A Comprehensive Literature Review

Daria Maria Filippini et al. Diagnostics (Basel). .

Abstract

Head and neck cancers (HNCs) arise from anatomically adjacent sites and subsites, with varying etiological factors, diagnostic strategies, prognoses, and treatment approaches. While conventional squamous cell carcinoma (SCC) is the most common histology in the head and neck district, HNCs encompass a variety of rare histopathological entities, categorized into epithelial tumors such as salivary gland cancers, sinonasal tumors, neuroendocrine tumors, malignant odontogenic tumors, and SCC variants versus non-epithelial tumors including soft tissue sarcomas, mucosal melanomas, and hematological malignancies. Rare HNCs (R-HNCs) represent a diagnostic and clinical challenge, requiring histopathological expertise, the availability of peculiar molecular analysis, and the personalization of local and systemic treatments, all guided by a multidisciplinary tumor board. Here, we provide a comprehensive literature review on R-HNCs, emphasizing key histopathological and molecular characteristics that are crucial for guiding treatment decisions. An insight about the latest developments in systemic treatments is also reported.

Keywords: head and neck cancer; histopathological diagnosis; molecular diagnostics; multidisciplinary care; rare cancers.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
H&E undifferentiated NK-NPC. (a) Spindly tumor cells (40×): the nuclei have fine chromatin and small, distinct nucleoli; (b) the tumor cells show immunoreactivity for cytokeratin and p63 supporting their epithelial nature; (c) positive labeling of the tumor cell nuclei for EBV-encoded small RNAs (EBERs) on in situ hybridization supports the diagnosis of nasopharyngeal carcinoma.
Figure 2
Figure 2
Salivary duct carcinoma in pleomorphic adenoma (carcinoma ex pleomorphic adenoma). (a) On H&E (5×), complex architecture with cribriforming glands and a Roman-bridge pattern; (b) strong immunopositivity for androgen receptors (ARs) in salivary duct carcinoma on the right and negativity of the component of pleomorphic adenoma; (c) HER2 overexpression cells: a strong complete membrane staining is observed in >10% of tumor cells.
Figure 2
Figure 2
Salivary duct carcinoma in pleomorphic adenoma (carcinoma ex pleomorphic adenoma). (a) On H&E (5×), complex architecture with cribriforming glands and a Roman-bridge pattern; (b) strong immunopositivity for androgen receptors (ARs) in salivary duct carcinoma on the right and negativity of the component of pleomorphic adenoma; (c) HER2 overexpression cells: a strong complete membrane staining is observed in >10% of tumor cells.
Figure 3
Figure 3
Mucoepidermoid carcinoma. (a) On H&E (10×), cystic spaces are partly lined by mucous cells. Other cell types include intermediate, squamoid, and partly clear cells; (b) FISH result positive for MAML2 rearrangement.
Figure 4
Figure 4
ITAC. (a) A moderately differentiated tumor with a tubular arrangement of neoplastic cells on H&E (10×); (b) the tumor cells show immunoreactivity for CDX2, supporting their intestinal differentiation.
Figure 4
Figure 4
ITAC. (a) A moderately differentiated tumor with a tubular arrangement of neoplastic cells on H&E (10×); (b) the tumor cells show immunoreactivity for CDX2, supporting their intestinal differentiation.
Figure 5
Figure 5
Malignant melanoma. (a) (10×) Epithelioid tumor cells infiltrating the basal layer of squamous epithelium as single cells on the left and the nodular infiltrating component on the right; (b) at higher magnification (40×), epithelioid tumor cells with amphophilic cytoplasm, large nuclei, and prominent nucleoli are arranged in solid sheets. Melanin is present.
Figure 6
Figure 6
Extranodal NK/T-cell lymphoma (ENKTL). (a) (10×) The lymphoma shows medium to large tumor cells with irregular and often hyperchromatic nuclei associated with nested hyperplastic squamous epithelium; (b) positive labelling of the tumor cell nuclei for EBV-encoded small RNAs (EBERs) on in situ hybridization; (c) positive CD56 in neoplastic cells.
Figure 7
Figure 7
High-grade osteoblastic osteosarcoma. (a) Malignant-appearing polyhedral and spindle cells producing an immature osteoid matrix on H&E (10×); (b) at higher magnification (40×), neoplastic cells with a lace-like pattern. Abundant mitoses are revealed.
Figure 8
Figure 8
Solitary fibrous tumor. (a) On H&E (10×), refractile collagen associated with a modestly cellular, monotonous spindled cell neoplastic proliferation. The neoplastic cells have a syncytial quality, with bland, elongated, oval nuclei with scant cytoplasm; (b) a strong and diffuse nuclear reaction for STAT6 immunohistochemistry.
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