Frankly Invasive Carcinoma Ex-intraductal Carcinoma: Expanding on an Emerging and Perplexing Concept in Salivary Gland Tumor Pathology

McLean-Holden, Anne C.; Rooper, Lisa M.; Lubin, Daniel; Magliocca, Kelly R.; Manucha, Varsha; Sadow, Peter M.; Tobias, Jonathan; Vargo, Richard J.; Thompson, Lester D.�R.; Heidarian, Amin; Weinreb, Ilan; Wenig, Bruce M.; Gagan, Jeffrey; Hernández-Prera, Juan C.; Bishop, Justin A.

doi:10.1007/s12105-021-01408-3

Cited by 11 publications

(34 citation statements)

References 25 publications

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“…metatypical adenoid cystic carcinoma with MYB fusions and frankly invasive intraductal carcinoma with RET or ALK fusions). [1][2][3][4][5] As a result, immunohistochemistry and molecular testing have both become standard practice in evaluating salivary gland tumours.…”

Section: Introductionmentioning

confidence: 99%

“…ETV6 fusions in secretory carcinoma and MEF2C::SS18 fusions in microsecretory adenocarcinoma) and refined the spectrum of how established neoplasms may appear (e.g. metatypical adenoid cystic carcinoma with MYB fusions and frankly invasive intraductal carcinoma with RET or ALK fusions) 1–5 . As a result, immunohistochemistry and molecular testing have both become standard practice in evaluating salivary gland tumours.…”

Section: Introductionmentioning

confidence: 99%

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Mucoepidermoid carcinoma may be devoid of squamoid cells by immunohistochemistry: expanding the histologic and immunohistochemical spectrum of MAML2‐ rearranged salivary gland tumours

et al. 2022

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Mucoepidermoid carcinoma (MEC) is historically defined by a mix of squamoid, intermediate, and mucous cells, but we have recently encountered several cases lacking immunoreactivity for squamous markers p40, p63, and CK5/6 despite MAML2 fusions. This study will characterise these unique tumours. Ten MEC were collected arising from the parotid gland (n = 4), submandibular gland (n = 2), nasopharynx (n = 1), base of tongue (n = 1), bronchus (n = 1), and trachea (n = 1). Six tumours were low‐grade, two intermediate‐grade, one high‐grade, and one demonstrated low‐grade areas with high‐grade transformation. Four cases were oncocytic, four had clear‐cell features, two had spindle cell features, and one high‐grade MEC had prominent solid, cord‐like, and micropapillary features. The tumours were negative for p40 (10/10), p63 (10/10), and CK5/6 (9/9). Targeted RNA sequencing demonstrated CRTC1::MAML2 in five cases, CRTC3::MAML2 in two, and a novel MAML2::CEP126 in the unusual high‐grade case. In two cases with insufficient RNA, MAML2 fluorescence in situ hybridisation (FISH) showed rearrangement. Genetically‐confirmed MEC may lack overt squamous differentiation by histology and immunohistochemistry. While most cases harboured canonical fusions and fit within the spectra of MEC variants with oncocytic, clear cell, and/or spindle cell features, one had a novel MAML2::CEP126 fusion and unusual morphology. In MEC without squamoid cells, the use of immunohistochemistry may hinder, rather than aid, the correct diagnosis. In such cases, MAML2 analysis is most useful. The historical definition of MEC as a carcinoma with squamoid, intermediate and mucous cells should be revisited.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Mucoepidermoid carcinoma may be devoid of squamoid cells by immunohistochemistry: expanding the histologic and immunohistochemical spectrum of MAML2‐ rearranged salivary gland tumours

et al. 2022

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“…Although typical intercalated‐type IDC has banal appearing “low grade” nuclei, the apocrine subset has large nuclei, granular eosinophilic cytoplasm, and macronucleoli 2,70 . To further complicate the morphologic distinction between IDC and SDC, McLean‐Holden et al 71 have described examples of invasive carcinoma ex‐IDC some of which “were indistinguishable from SDC, with clear‐cut apocrine differentiation.” A recently described cytologic series (13 cases of IDC) showed features in the H‐G form that strongly imitate those of classic SDC 72 . The authors admit that due to overlapping features with other SG neoplasms, a definitive FNA diagnosis of IDC using only cytomorphology is not possible, and a firm diagnosis requires ancillary IHC and probably molecular profiling.…”

Section: Discussionmentioning

confidence: 99%

Salivary duct carcinoma: A report of 70 FNA cases and review of the literature

Wakely

2022

Cancer Cytopathology

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BACKGROUND:Although usually recognized as malignant, fine-needle aspiration (FNA) biopsy of salivary duct carcinoma (SDC) has been confused with other primary salivary gland (SG) neoplasms. This article undertook an analysis of a large collection of SDC FNA cases to assess diagnostic accuracy, specificity, and cytopathology. METHODS: Cytopathology files were searched for SDC with histopathologic validation. FNA biopsy smears were performed using standard techniques. RESULTS:Seventy cases from 56 patients (M:F, 1.9:1; age range, 26-92 years; mean age, 65 years) met inclusion criteria. All had tissue confirmation of SDC. FNA sites included: parotid gland (42, 60% cases), neck (10), submandibular gland (7), pre-/ post-auricular area (5), face/cheek (3), mediastinal lymph nodes (2), and clavicle (1). Aspirates were from primary (52, 74%), metastatic (12, 17%), and locally recurrent (6, 9%) neoplasms. FNA diagnoses included: SDC (19, 27%), favor/suspicious for SDC (7, 10%), high-grade carcinoma (11), adenocarcinoma ( 9), carcinoma ( 6), malignant (6), SG neoplasm (5), atypia (3), SDC versus another malignancy (2), and pleomorphic adenoma (2). Large polygonal cells in groups and single forms showed cribriforming, variable necrosis, pseudopapillae, and oncocytic change. Androgen receptor staining was positive in all cases.CONCLUSIONS: FNA biopsy is accurate and reliable in classifying SDC as a malignant neoplasm, but much less so for identification as a specific tumor type. Using the Milan system, 86% of aspirates were classified as either malignant or suspicious for malignancy. A recurring pitfall includes sampling error in cases of SDC ex pleomorphic adenoma. Cancer Cytopathol 2022;130:595-608.

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“…3D), and are the features that must be actively confirmed. 13,33,46,50 The concept that the frankly invasive component represents a high-grade transformation of the underlying tumor category may occur in some cases, but not all destructively invasive tumors have a high-grade histology and some tumors do not fit within a specific category at all (i.e., not otherwise specified). 50 With several different frankly invasive tumor types, providing information about grade and extent of invasion seems prudent.…”

Section: Microscopic Featuresmentioning

confidence: 99%

“…6,9,[11][12][13]26,30,32,33,49,50,83 When reported, the epithelial cells are reactive with pancytokeratin (AE1/AE3), CAM5.2, 34ßE12 (K903), CK7, EMA, and CK19. 6,9,[11][12][13]26,30,32,33,49,50,83 Variable reactivity is reported with GATA3 and DOG1 (although only rarely positive for the latter). 26,29,34,43,49,50 Neoplastic cells are nonreactive with estrogen receptor and progesterone receptor.…”

Section: Immunohistochemistry and In Situ Hybridization Findingsmentioning

confidence: 99%

Salivary Gland Intraductal Carcinoma: How Do 183 Reported Cases Fit Into a Developing Classification

Thompson

Bishop

2022

Advances in Anatomic Pathology

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Salivary gland intraductal carcinoma (IDC) is a very uncommon group of neoplasms. Many names, variations in diagnostic criteria, and newly observed molecular findings (including NCOA4::RET, TRIM27::RET, HRAS point mutations, and PIK3CA pathway alterations) have generated further confusion in being able to recognize and categorize this group of tumors. Different histologic appearances and patterns of growth suggest there is more than one tumor category, with intercalated duct, apocrine, oncocytic, and hybrid features seen. Frankly destructive invasion further complicates the category, as the name "intraductal" would suggest an "in situ" neoplasm. Recent evidence on fusion-positive IDC demonstrates the same molecular underpinnings in both the ductal and the myoepithelial cells, which aids in further separating these tumors. This article summarizes the historical group of 183 neoplasms classified under the umbrella of IDC and highlights the unique histologic, immunohistochemistry, and molecular features that may further guide nomenclature standardization and harmonization.

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Frankly Invasive Carcinoma Ex-intraductal Carcinoma: Expanding on an Emerging and Perplexing Concept in Salivary Gland Tumor Pathology

Cited by 11 publications

References 25 publications

Mucoepidermoid carcinoma may be devoid of squamoid cells by immunohistochemistry: expanding the histologic and immunohistochemical spectrum of MAML2‐ rearranged salivary gland tumours

Mucoepidermoid carcinoma may be devoid of squamoid cells by immunohistochemistry: expanding the histologic and immunohistochemical spectrum of MAML2‐ rearranged salivary gland tumours

Salivary duct carcinoma: A report of 70 FNA cases and review of the literature

Salivary Gland Intraductal Carcinoma: How Do 183 Reported Cases Fit Into a Developing Classification

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