Neurofilament is superior to cytokeratin 20 in supporting cutaneous origin for neuroendocrine carcinoma

Stanoszek, Lauren M.; Chan, May P.; Palanisamy, Nallasivam; Carskadon, Shannon; Siddiqui, Javed; Patel, Rajiv M.; Harms, Paul W.; Lowe, Lori; Fullen, Douglas R.

doi:10.1111/his.13758

Cited by 32 publications

(19 citation statements)

References 37 publications

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“…The IHC positivity of NF-L is also seen in neuroendocrine tumors in a few sites including cutaneous tissue, gastrointestinal tract, breast, lung, and mediastinum, [23][24][25] as well as the testis and testicular germ-cell tumors. 22 The presence of NF-L in the testis and testicular germ-cell tumors has been attributed to the involvement of neural tissue.…”

Section: Discussionmentioning

confidence: 99%

Immunohistochemical Markers in the Diagnosis of Calcifying Pseudoneoplasm of the Neuraxis

Yang

Reddy

Wang

et al. 2020

Can. J. Neurol. Sci.

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Background: Calcifying pseudoneoplasm of the neuraxis (CAPNON) is a rare tumor-like lesion with unknown pathogenesis. It is likely under-reported due to diagnostic challenges including the nonspecific radiographic features, lack of diagnostic markers, and often asymptomatic nature of the lesions. Methods: We performed detailed examination of 11 CAPNON specimens diagnosed by histopathology, with the help of electron microscopy and immunohistochemistry. Results: Electron microscopy revealed the presence of fibrillary materials consistent with neurofilaments. In addition to some entrapped axons at the periphery of CAPNONs, we discovered that all specimens stained positive for neurofilament-light (NF-L) within the granular amorphous cores, but not neurofilament-phosphorylated (NF-p). CAPNONs also showed variable infiltration of CD8+ T-cells and a decreased ratio of CD4/CD8+ T-cells, suggesting an immune-mediated process in the pathogenesis of CAPNON. Conclusion: NF-L and CD4/CD8 immunostains may serve as diagnostic markers for CAPNON and shed light on its pathogenesis.

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Section: Discussionmentioning

confidence: 99%

Immunohistochemical Markers in the Diagnosis of Calcifying Pseudoneoplasm of the Neuraxis

Yang

Reddy

Wang

et al. 2020

Can. J. Neurol. Sci.

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“…Neurofilament is frequently expressed by Merkel cell carcinoma (75%) and less commonly by tumors of lung or extrapulmonary visceral origin [2,125]. When I examined neurofilament in my laboratory (clone 2F11), I found staining in 67% of 39 Merkel cell, 17% of 24 small cell lung, and 6% of 18 extrapulmonary visceral NECs [126].…”

Section: Neuroendocrine Carcinomasmentioning

confidence: 99%

Immunohistochemistry in the diagnosis and classification of neuroendocrine neoplasms: what can brown do for you?

2020

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This review is based on a presentation given at the Hans Popper Hepatopathology Society companion meeting at the 2019 United States and Canadian Academy of Pathology Annual Meeting. It presents updates on the diagnosis and classification of neuroendocrine neoplasms, with an emphasis on the role of immunohistochemistry. Neuroendocrine neoplasms often present in liver biopsies as metastases of occult origin. Specific topics covered include 1. general features of neuroendocrine neoplasms, 2. general neuroendocrine marker immunohistochemistry, with discussion of the emerging marker INSM1, 3. non-small cell carcinoma with (occult) neuroendocrine differentiation, 4. the WHO Classification of neuroendocrine neoplasms, with discussion of the 2019 classification of gastroenteropancreatic neoplasms, 5. use of Ki-67 immunohistochemistry, 6. immunohistochemistry to assign site of origin in neuroendocrine metastasis of occult origin, 7. immunohistochemistry to distinguish well-differentiated neuroendocrine tumor G3 from poorly differentiated neuroendocrine carcinoma, 8. lesions frequently misdiagnosed as well-differentiated neuroendocrine tumor, and 9. required and recommended data elements for biopsies and resections with associated immunohistochemical stains. Next-generation immunohistochemistry, including lineage-restricted transcription factors (e.g., CDX2, islet 1, OTP, SATB2) and protein correlates of molecular genetic events (e.g., p53, Rb), is indispensable for the accurate diagnosis and classification of these neoplasms.

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“…26 Perinuclear staining with cytokeratin 20 (CK-20) (Figure 3c) has approximately 95% sensitivity and 60% specificity. 27,28 The identification and mainstream production of CK20 as an MCC marker has improved MCC identification since at least 1997. 29 Neurofilament protein (Figure 3d) has lower sensitivity but good specificity and is used to detect CK-20 negative and VN-MCC, with 96.7% specificity.…”

Section: Diagnosismentioning

confidence: 99%

Merkel cell carcinoma

Mistry

Levell

Craig

et al. 2021

Skin Health and Disease

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Merkel cell carcinoma (MCC) is a rare neuroendocrine carcinoma. The cellular origin of MCC may include Merkel cell precursors. The incidence of MCC has increased significantly however trends may have been confounded by evolving diagnostic criteria. The two key aetiologies of MCC are ultraviolet radiation and Merkel cell polyoma virus (MCPyV). Both have unique mechanisms of carcinogenesis. MCC presents non-specifically as a rapidly growing, red-to-violet nodule on sun-exposed areas. Diagnostic accuracy has improved through immunohistochemical markers such as CK-20. Lymph nodes should be evaluated in MCC through examination and sentinel biopsy. USS, CT, MRI and CT-PET may be useful in staging. Management depends on tumour location, stage and comorbidities. MCPyV status may guide treatment strategy in the future. Treatment for the primary MCC is commonly wide local excision followed by radiotherapy, guided by anatomical constraints. There is uncertainty about surgical margins. Treatments for nodal disease have not been determined through trials. They include nodal dissection or radiotherapy for clinically or radiologically apparent disease, and adjuvant nodal irradiation for negative nodes, microscopic disease or following nodal dissection for definite disease. Patients with loco-regional advanced inoperable disease should be considered for combination therapy including chemotherapy, radiotherapy, surgery and immunotherapy. Systemic therapy for advanced disease includes immune checkpoint inhibitors targeting the PD-1/PD-L1 pathway. Avelumab can improve survival in metastatic MCC. Immunotherapy may result in longer disease control. Various other immunotherapeutic and molecular agents are undergoing trials. MCC continues to have a high mortality characterized by high recurrence and early metastases. | INTRODUCTIONThis review article presents a concise update of knowledge in these areas relevant to the clinician. This review will discuss the pathogenesis, epidemiology, diagnosis, staging, treatment and prognosis of Merkel cell carcinoma (MCC). | PATHOGENESISMCC is a rare, aggressive neuroendocrine carcinoma first described in Baltimore, USA by Cyril Toker in 1972. 1 Merkel cells are postmitotic neuroendocrine cells in the basal epidermis which secrete amine and polypeptide hormones. Despite the name, it is unlikelyThis is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

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Neurofilament is superior to cytokeratin 20 in supporting cutaneous origin for neuroendocrine carcinoma

Cited by 32 publications

References 37 publications

Immunohistochemical Markers in the Diagnosis of Calcifying Pseudoneoplasm of the Neuraxis

Immunohistochemical Markers in the Diagnosis of Calcifying Pseudoneoplasm of the Neuraxis

Immunohistochemistry in the diagnosis and classification of neuroendocrine neoplasms: what can brown do for you?

Merkel cell carcinoma

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