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Sweat-gland carcinoma with neuroendocrine differentiation (SCAND): a clinicopathologic study of 13 cases with genetic analysis

Abstract

Low-grade neuroendocrine carcinoma of the skin (LGNECS) was proposed in 2017 as a new primary cutaneous neoplasm with neuroendocrine differentiation; however, it is not yet well known due to its rarity. Herein, we perform a detailed clinicopathologic analysis of 13 cases as well as panel DNA sequencing in three cases. The study included 12 males and 1 female with a median age of 71 (43–85) years. All lesions occurred on the ventral trunk. The mean tumor size was 2.2 (0.8–11.0) cm. The histopathology resembled that of well-differentiated neuroendocrine tumors (NETs) in other organs, but intraepidermal pagetoid spreading was seen in 8 (61.5%) cases and stromal mucin deposits in 4 (30.8%). Immunoreactivity for CK7, CK19, EMA, BerEP4, CEA, chromogranin A, synaptophysin, INSM1, GCDFP15, GATA3, ER, and bcl-2 were present in varying degrees in all tested cases. PTEN c.165-1G>A splice site mutation was detected by panel sequencing in one case, and GATA3 P409fs*99 and SETD2 R1708fs*4 in another case. Lymph node metastasis was seen significantly in cases with tumor size >2.0 cm [8/8 (100%) vs. 1/5 (20%)]. All three cases with size >3.0 cm were in unresectable advanced-stage [3/3 (100%) vs. 1/10 (10%)], and two of the three patients succumbed to the disease. The two cases of death revealed mild nuclear atypia (mitosis: 1/10 HPFs) and moderate nuclear atypia (2/10 HPFs). Thus, tumor size would be a better prognostic factor than nuclear atypia, mitotic count, and Ki67 index, unlike in NETs. These clinicopathologic and immunohistochemical features would represent the characteristics as skin adnexal tumors with apocrine/eccrine differentiation rather than NETs; therefore, we rename it as sweat-gland carcinoma with neuroendocrine differentiation (SCAND).

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Fig. 1: Clinical findings of sweat-gland carcinoma with neuroendocrine differentiation (SCAND)/low-grade neuroendocrine carcinoma of the skin (LGNECS).
Fig. 2: Tumor silhouettes of sweat-gland carcinoma with neuroendocrine differentiation (SCAND)/low-grade neuroendocrine carcinoma of the skin (LGNECS).
Fig. 3: Histopathologic findings of sweat-gland carcinoma with neuroendocrine differentiation (SCAND)/low-grade neuroendocrine carcinoma of the skin (LGNECS).
Fig. 4: Nuclear atypia of sweat-gland carcinoma with neuroendocrine differentiation (SCAND)/low-grade neuroendocrine carcinoma of the skin (LGNECS).
Fig. 5: Immunohistochemical findings of sweat-gland carcinoma with neuroendocrine differentiation (SCAND)/low-grade neuroendocrine carcinoma of the skin (LGNECS).

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Acknowledgements

The authors thank Ms. Fujiko Ishimoto and Mr. Kikuichi Nakagawa for their superb technique.

Funding

Supported in part by OICI fund for Department of Dermatologic Oncology in 2020.

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K.G. designed the study, analysed the clinicopathologic data, and wrote and edited the paper. Y.K. analyzed the molecular data of the samples. All authors provided the cases, extracted the clinical data, reviewed the paper, and gave the final approval for publication.

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Correspondence to Keisuke Goto.

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The authors declare no competing interests.

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The study was conducted according to the Declaration of Helsinki and has been approved by the research ethics committee of the Osaka International Cancer Institute, Osaka, Japan (reference number: 20113).

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Goto, K., Kukita, Y., Honma, K. et al. Sweat-gland carcinoma with neuroendocrine differentiation (SCAND): a clinicopathologic study of 13 cases with genetic analysis. Mod Pathol (2021). https://doi.org/10.1038/s41379-021-00921-8

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