Well‐differentiated neuroendocrine tumors in skin: Terminology and diagnostic utility of cytokeratin 5/6 and p63

Panse, Gauri; Cowper, Shawn E.; Leffell, David J.; Pulitzer, Melissa; Ko, Christine J.

doi:10.1111/cup.12952

Cited by 6 publications

(10 citation statements)

References 20 publications

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“…5 Other than MCC, cutaneous neoplasms with at least focal neuroendocrine features include basal cell carcinoma and adnexal neoplasms. 4,[23][24][25][26] By definition, MCC shows high-grade histopathologic features including infiltrative growth, nuclear pleomorphism, and high mitotic index. This contrasts with primary cutaneous low-grade neuroendocrine tumors, which are also included in the differential of cutaneous neuroendocrine neoplasms, and analogous to carcinoid tumors arising in other sites.…”

Section: Discussionmentioning

confidence: 99%

Cutaneous metastases of non‐cutaneous neuroendocrine neoplasms: A histopathologic review of 15 cases

et al. 2022

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Background: Cutaneous metastases from non-cutaneous neuroendocrine neoplasms are rare; however, distinction from primary neuroendocrine carcinomas of the skin (Merkel cell carcinoma) guides clinical management. Methods:We performed a retrospective review from September 1, 2010 to September 30, 2020 of the histopathologic, immunohistochemical, and clinical characteristics of metastatic neuroendocrine neoplasms to the skin from non-cutaneous primaries.Results: Fourteen patients were identified for the study (nine males and five females; mean age of 59.5 years). Fifteen skin specimens from 14 patients were available for review. At the time of skin biopsy, a known non-cutaneous neuroendocrine neoplasm was present in 50% of patients. Primary sites of neuroendocrine carcinoma included lung (n = 5), terminal ileum (n = 2), and one each from prostate, breast, rectum, uterus, esophagus, and sinus, with one unknown (suspected bladder malignancy). Eleven of fourteen patients are dead of disease; one was lost to follow-up. All 15 specimens showed subcutaneous/deep dermal involvement with six involving the papillary dermis and one involving the epidermis. The tumors ranged from well to poorly differentiated. Two of fifteen specimens showed focal CK20 positivity (one metastatic uterine small cell carcinoma and one metastatic ileal carcinoid). TTF-1 was performed in 13 specimens and was positive in six, of which two were of non-pulmonary origin.Conclusions: While immunohistochemical stains, in particular CK20, CK7, and TTF-1, are integral in the workup of confirming the origin of neuroendocrine tumors found in the skin, results vary and are often non-specific for a single primary site. Therefore, complete radiologic imaging as well as clinical correlation should be recommended to further aid in the identification of a non-cutaneous primary neoplasm.

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Section: Discussionmentioning

confidence: 99%

Cutaneous metastases of non‐cutaneous neuroendocrine neoplasms: A histopathologic review of 15 cases

et al. 2022

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“…LGNECS tumors are extremely rare with only 19 reported cases to date . They typically occur as a single flesh‐colored nodule with an average size of 3.2 cm, with a predilection for the scalp and trunk.…”

Section: Discussionmentioning

confidence: 99%

“…The patient's lesion is relatively well circumscribed and located in the dermis and subcutaneous soft tissue with no connection with the epidermis LGNECS tumors are extremely rare with only 19 reported cases to date. 7,11 They typically occur as a single flesh-colored nodule with an average size of 3.2 cm, with a predilection for the scalp and trunk.…”

Section: Discussionmentioning

confidence: 99%

“…In summary, we describe the 19th case of LGNECS 7,8,[11][12][13] and the 2nd case of LGNECS with metastasis. 13 While this entity is extremely rare, it is important to be cognizant of it because the treatment, prognosis and clinical behavior of LGNECS differs vastly from the other differential diagnoses of NET of the skin that are much more aggressive including MCC, extracutaneous metastatic NET and small-cell variant of melanoma.…”

Section: Discussionmentioning

confidence: 99%

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Primary low‐grade neuroendocrine carcinoma of the skin: An exceedingly rare entity

Chen

Morrison²,

Susa

et al. 2017

J Cutan Pathol

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Low-grade neuroendocrine tumors (NETs), also known as carcinoid tumor, commonly arise from the gastrointestinal (GI) and pulmonary tracts, but rarely occur in the skin. Cutaneous NET typically occurs as metastases or high-grade primary lesions, called Merkel cell carcinoma. In the few cases described in literature, primary low-grade neuroendocrine carcinomas of the skin (LGNECS) are usually indolent cutaneous nodules, presenting on the head and trunk of elderly patients. LGNECS tumors are histologically similar to its counterparts arising in other anatomic locations. As there is no NET cut-off for the skin due to their rarity, the GI scale was used instead; low-grade NETs have a Ki-67 proliferative index of less than 3%. The distinction between primary and metastatic NET, however, is not absolute and can be difficult. A primary vs metastatic NET diagnosis relies on clinical exclusion of a NET in other, more common, anatomic locations. Here, we present a case of an LGNECS on the scalp of a 72-year-old female patient. Whole body imaging failed to identify any octreotide-avid lesions elsewhere in the patient, aside from 2 positive cervical lymph nodes, which were confirmed with a node dissection and histologic evaluation. This is the 19th reported case of LGNECS and the 2nd reported case of LGNECS with nodal metastasis.

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“…Another challenge for pathologists can be well-differentiated neuroendocrine tumours (WDNT) that originate in the stomach or lungs and can metastasise to skin. A total of 10 out of 10 samples of WDNT tested negative for p63, which can be useful in distinguishing them from CANs [106].…”

Section: Diagnostic and Prognostic Value Of P63 In Skin Cancermentioning

confidence: 99%

p63 Is a Promising Marker in the Diagnosis of Unusual Skin Cancer

Smirnov

Anemona

Novelli

et al. 2019

IJMS

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Skin cancer is the most common type of cancer worldwide. Ozone depletion and climate changes might cause a further increase in the incidence rate in the future. Although the early detection of skin cancer enables it to be treated successfully, some tumours can evolve and become more aggressive, especially in the case of melanoma. Therefore, good diagnostic and prognostic markers are needed to ensure correct detection and treatment. Transcription factor p63, a member of the p53 family of proteins, plays an essential role in the development of stratified epithelia such as skin. In this paper, we conduct a comprehensive review of p63 expression in different types of skin cancer and discuss its possible use in the diagnosis and prognosis of cutaneous tumours.

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Well‐differentiated neuroendocrine tumors in skin: Terminology and diagnostic utility of cytokeratin 5/6 and p63

Abstract: Negative staining for CK5/6 and p63 can be helpful to distinguish WDNETs from cutaneous adnexal neoplasms. It is important to consider WDNETs in the differential diagnosis of cutaneous adnexal neoplasms as low-grade tumors may be the first sign of aggressive metastatic disease.

Cited by 6 publications

References 20 publications

Cutaneous metastases of non‐cutaneous neuroendocrine neoplasms: A histopathologic review of 15 cases

Cutaneous metastases of non‐cutaneous neuroendocrine neoplasms: A histopathologic review of 15 cases

Primary low‐grade neuroendocrine carcinoma of the skin: An exceedingly rare entity

p63 Is a Promising Marker in the Diagnosis of Unusual Skin Cancer

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