Skin nonmelanocytic tumor
Adnexal tumors
Sweat gland derived (apocrine & eccrine glands)
Cutaneous adnexal NUT carcinoma
Editorial Board Member: Farres Obeidin, M.D.
Last staff update: 8 July 2024 (update in progress)
Copyright: 2024-2024, PathologyOutlines.com, Inc.
PubMed Search: Cutaneous adnexal NUT carcinoma
Table of Contents
Definition / general | Essential features | Terminology | ICD coding | Epidemiology | Sites | Pathophysiology | Etiology | Clinical features | Diagnosis | Radiology description | Radiology images | Prognostic factors | Case reports | Treatment | Microscopic (histologic) description | Microscopic (histologic) images | Virtual slides | Positive stains | Negative stains | Molecular / cytogenetics description | Molecular / cytogenetics images | Sample pathology report | Differential diagnosis | Additional references | Board review style question #1 | Board review style answer #1 | Board review style question #2 | Board review style answer #2Cite this page: Tseng C, Saeed Kamil Z. Cutaneous adnexal NUT carcinoma. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/skinnonmelanocyticcutaneousadnexalNUT.html. Accessed July 15th, 2024.
Definition / general
- Rare, provisional primary cutaneous carcinoma of adnexal origin showing NUTM1 or NUTM2B fusion with BRD4 interacting partners (BRD3 and NSD3)
Essential features
- Histological features appear to differ based on the underlying molecular fusion
- In general, histological features include a biphasic population of epithelial round luminal and basal cells forming cords and nests, duct formation and may have follicular keratocysts
- Cells show round nuclei, vesicular chromatin and prominent nucleoli
- Immunohistochemical features include diffuse positivity for CK AE1 / AE3, EMA
- NUT1 and SOX10 are often positive
- Luminal cells are positive for CK7
- Basal cells are positive for p40, p63 and CK5
- Defined by identifying NUTM1 or NUTM2B fusions with BRD4 interacting partners (i.e., BRD3, NSD3) and excluding extracutaneous NUT carcinoma
- Has metastatic potential but is much less aggressive than extracutaneous NUT carcinoma (J Cutan Pathol 2024;51:424)
Terminology
- NUT carcinoma, NUT adnexal carcinoma
- Not recommended: BRD3::NUTM2B adnexal carcinoma (BNAC), NUT midline carcinoma, BRD3::NUTM1 adnexal carcinoma, NSD3::NUTM1 adnexal carcinoma
ICD coding
- ICD-O: 8023/3 - NUT carcinoma
- ICD-11: 2D42 & XH2855 - malignant neoplasms of ill defined sites & nuclear protein in testis (NUT) associated carcinoma
Epidemiology
- Currently 6 cases reported in the literature (J Cutan Pathol 2021;48:1508, Am J Surg Pathol 2021;45:1582, Am J Surg Pathol 2021;45:1584, J Cutan Pathol 2024;51:424, Am J Surg Pathol 2023;47:1096)
- 7 - 59 years old (median: 42 years old) (J Cutan Pathol 2021;48:1508, Am J Surg Pathol 2021;45:1582, Am J Surg Pathol 2021;45:1584)
- Sex available for 4 cases: 3 women, 1 man (J Cutan Pathol 2021;48:1508, Am J Surg Pathol 2021;45:1582, Am J Surg Pathol 2021;45:1584)
Sites
- No known site predilection; isolated cases involving the inguinal area and extremities (Am J Surg Pathol 2021;45:1582, Am J Surg Pathol 2021;45:1584, J Cutan Pathol 2021;48:1508, J Cutan Pathol 2024;51:424)
Pathophysiology
- Pathophysiology of primary cutaneous NUT carcinoma has not been directly investigated; however, in extracutaneous NUT carcinoma, NUTM1 or NUTM2B fusions with bromodomain containing protein (BRD) 4 or BRD4 interacting partners (BRD3, nuclear receptor binding SET domain protein 3 [NSD3]) lead to expression of MYC and SOX2, along with inactivation of p53, resulting in increased growth and blockage of differentiation (Genes Dev 2015;29:1507, Cancer Res 2014;74:3332, J Cutan Pathol 2024;51:424)
Etiology
- Unknown
Clinical features
- May present as a subcutaneous nodule or dermal lesion (J Cutan Pathol 2021;48:1508, Am J Surg Pathol 2021;45:1582, Am J Surg Pathol 2021;45:1584)
- May be present for years or present with concurrent lymph node metastasis (Am J Surg Pathol 2021;45:1584)
Diagnosis
- Biopsy
- Defined by histological features and molecular findings of fusion between a member of NUT family (NUTM1 or NUTM2B) with BRD4 interacting partners (BRD3 and NSD3)
- Clinical exclusion of metastatic extracutaneous NUT carcinoma
Radiology description
- Subcutaneous mass may be identified on imaging (J Cutan Pathol 2024;51:424)
Radiology images
Images hosted on other servers:
Subcutaneous tumor MRI
Prognostic factors
- Prognosis appears significantly better than extracutaneous NUT carcinoma but cutaneous cases are few and follow up is limited (J Cutan Pathol 2021;48:1508, Am J Surg Pathol 2021;45:1582, Am J Surg Pathol 2021;45:1584, J Cutan Pathol 2024;51:424)
- Insufficient data to suggest whether different fusion partners are associated with different prognoses (J Cutan Pathol 2024;51:424)
Case reports
- 7 year old girl with nodule on shoulder and sentinel lymph node metastasis (J Cutan Pathol 2021;48:1508)
- 34 year old woman with left leg cutaneous tumor and left inguinal subcutaneous lymph node metastasis (Am J Surg Pathol 2021;45:1584)
- 46 year old woman with right inguinal subcutaneous mass (Am J Surg Pathol 2021;45:1582)
- 59 year old man with tumor of plantar foot (J Cutan Pathol 2024;51:424)
Treatment
- Surgical excision and lymph node dissection have been performed but optimal treatment is unknown (Am J Surg Pathol 2021;45:1582)
- Adjuvant radiotherapy and systemic chemotherapy has been offered (Am J Surg Pathol 2021;45:1582, J Cutan Pathol 2024;51:424)
Microscopic (histologic) description
- Based on currently available case reports, histology appears to differ based on the underlying fusion
- BRD3::NUTM1, BRD3::NUTM2B fusions
- Infiltrating strands, tubules or solid nodules of tumor cells in the dermis or subcutaneous tissue (Am J Surg Pathol 2021;45:1584)
- Follicular keratin cysts and focal ducts often identified in the neoplasm (J Cutan Pathol 2021;48:1508)
- May have biphasic architecture of luminal ductal cells and basal squamoid cells (J Cutan Pathol 2021;48:1508)
- Cytology may show poroid cells or clear cells (J Cutan Pathol 2021;48:1508)
- Cells are monotonous with prominent single nucleoli (Am J Surg Pathol 2021;45:1582)
- Mitotic activity may be identified (Am J Surg Pathol 2021;45:1584)
- May have abrupt keratinization (Am J Surg Pathol 2021;45:1584)
- Stroma may be desmoplastic (J Cutan Pathol 2021;48:1508)
- NSD3::NUTM1 fusions
- Ductal differentiation but no follicular keratocysts (Am J Surg Pathol 2023;47:1096)
- A case of possible primary cutaneous adnexal NUT carcinoma showing a BRD4::NUTM1 fusion was identified in a case report; more cases are necessary before definitive histological features can be confirmed (J Cutan Pathol 2024;51:424)
- Infiltrating trabeculae and nodules within a desmoplastic stroma (J Cutan Pathol 2024;51:424)
- Epithelioid cells with eosinophilic to clear cytoplasm, large vesicular nuclei and prominent nucleoli
- Foci of necrosis (J Cutan Pathol 2024;51:424)
- Poorly differentiated, with no ductal or follicular keratocyst formation (J Cutan Pathol 2024;51:424)
Microscopic (histologic) images
Contributed by Calvin Tseng, M.D. and Zaid Saeed Kamil, M.B.Ch.B.
Dermal lesion
Follicular differentiation
Biphasic ductal differentiation
Monomorphic cells
CK7
p40
p63
CK5
EMA
MYC
Virtual slides
Contributed by Calvin Tseng, M.D. and Zaid Saeed Kamil, M.B.Ch.B.
Cutaneous NUT carcinoma (BRD3::NUTM1)
Positive stains
- Luminal cells are positive for CK7 (Am J Surg Pathol 2021;45:1584)
- Basal cells are positive for p40, p63 and CK5 (Am J Surg Pathol 2021;45:1584, Am J Surg Pathol 2021;45:1582)
- CK AE1 / AE3 (Am J Surg Pathol 2021;45:1584)
- SOX10 in 3 of 4 cases (Am J Surg Pathol 2021;45:1584, J Cutan Pathol 2024;51:424, Am J Surg Pathol 2023;47:1096)
- EMA may be diffuse or heterogeneously positive (Am J Surg Pathol 2023;47:1096)
- CEA stains ductal structures (Am J Surg Pathol 2023;47:1096)
- MYC (current case)
- NUT is positive in 3 of 4 with NUTM1 fusion (Am J Surg Pathol 2021;45:1584)
- YAP1 C terminus retained (Am J Surg Pathol 2021;45:1582)
Negative stains
- NUT is negative in cases with NUTM2B fusion (J Cutan Pathol 2021;48:1508)
- Desmin (J Cutan Pathol 2024;51:424)
- CD34 (J Cutan Pathol 2024;51:424)
- S100 (J Cutan Pathol 2024;51:424)
Molecular / cytogenetics description
- BRD3 or NSD3 fusion with NUTM1 or NUTM2B; a case of possible primary cutaneous adnexal NUT carcinoma showing a BRD4::NUTM1 fusion was identified in a case report (J Cutan Pathol 2024;51:424)
- Excluded by YAP::NUTM1 fusion, which is seen in poroma and porocarcinomas (J Cutan Pathol 2024;51:424)
- Above fusions can be identified using next generation sequencing (NGS)
Molecular / cytogenetics images
Images hosted on other servers:
Less common BRD4::NUTM1 fusion
Sample pathology report
- Skin, excision, left leg:
- Cutaneous adnexal NUT carcinoma, completely excised (see comment)
- Maximum tumor size: X cm
- Maximum tumor thickness: X mm
- Perineural invasion: not identified / present
- Lymphovascular invasion: not identified / present
- Tumor is X mm away from the closest margin
- Comment: Based on limited case reports, NUT adnexal carcinomas have metastatic potential but appear to behave less aggressively than extracutaneous NUT carcinomas.
Differential diagnosis
- Metastatic extracutaneous NUT carcinoma:
- Identification of a primary tumor, most often in midline head and neck structures but can occur at many sites
- Sheet-like growth pattern instead of cords and strands
- May have chondroid mesenchymal differentiation
- Lack of prominent ductal differentiation and follicular keratocysts
- More aggressive behavior
- Porocarcinoma:
- Lacks follicular keratocysts
- Cytology may be more pleomorphic
- SOX10 mostly negative (J Clin Pathol 2023;76:649)
- May have fusions in YAP1::MAML2, YAP1::NUTM1, WWRT1:NUTM1
- Poroma:
- Benign tumor that lacks cytologic atypia and follicular keratocysts
- SOX10 mostly negative (J Clin Pathol 2023;76:649)
- May have fusions in YAP1::MAML2, YAP1::NUTM1, WWRT1:NUTM1
- Hidradenocarcinoma:
- Lacks follicular keratocysts
- NUT IHC negative
- May have fusions in CRTC1::MAML2 or CRTC3::MAML2
- Hidradenoma:
- Benign tumor with no cytologic atypia or follicular keratocysts
- SOX10 often negative (J Clin Pathol 2023;76:649)
- NUT IHC negative
- May have fusions in CRTC1::MAML2 or CRTC3::MAML2
- Squamous cell carcinoma:
- May have adjacent actinic keratosis or an in situ component
- Lacks follicular keratocysts and ducts
- NUT IHC negative
- Lacks NUTM1 fusions
Additional references
Board review style question #1
The tumor shown above is identified in the skin. Which of the following features favors the diagnosis of cutaneous adnexal NUT carcinoma over porocarcinoma?
- Negativity for SOX10 immunohistochemistry
- Positivity for NUT immunohistochemistry
- Presence of ductal differentiation
- Presence of follicular keratocysts
Board review style answer #1
D. Presence of follicular keratocysts. This histological feature favors cutaneous adnexal NUT carcinoma. Answer A is incorrect because SOX10 is often positive in cutaneous adnexal NUT carcinoma but usually negative in porocarcinoma. Answer B is incorrect because both entities are often positive for NUT immunohistochemistry. Answer C is incorrect because ductal differentiation is often seen in both entities.
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Reference: Cutaneous adnexal NUT carcinoma
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Reference: Cutaneous adnexal NUT carcinoma
Board review style question #2
Which of the following features favors the diagnosis of cutaneous adnexal NUT carcinoma over metastatic extracutaneous NUT carcinoma?
- Presence of abrupt keratinization
- Presence of chondroid differentiation
- Presence of ductal differentiation
- Presence of sheet-like growth
Board review style answer #2
C. Presence of ductal differentiation. This feature is not seen in metastatic extracutaneous NUT carcinoma. Answer A is incorrect because abrupt keratinization may be seen in metastases from both cutaneous adnexal NUT carcinoma and metastatic extracutaneous NUT carcinoma. Answer D is incorrect because sheet-like growth is more common in metastatic extracutaneous NUT carcinoma. Answer B is incorrect because chondroid differentiation has only been reported in extracutaneous NUT carcinoma.
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Reference: Cutaneous adnexal NUT carcinoma
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Reference: Cutaneous adnexal NUT carcinoma
