Top

Diagnostic Pathology

Published in:

Open Access 01-12-2021 | Melanoma | Research

Prognostic significance of the aberrant expression of neuroendocrine markers in melanomas

Authors: Yan Wu, Yumei Lai, Miao Zhang, Zhongwu Li

Published in: Diagnostic Pathology | Issue 1/2021

Abstract

Background

Melanoma is a highly malignant tumor with diverse histopathological morphology and frequent aberrant expression of immunohistochemical markers. An occasionally reported phenomenon is the abnormal expression of neuroendocrine markers. Awareness of this situation is essential because such tumors need to be differentiated from neuroendocrine tumors because of their significant therapeutic and prognostic implications.

Methods

We retrospectively analyzed the expression of chromogranin A (CgA), synaptophysin (Syn) and CD56 as neuroendocrine markers in 308 cases with melanomas. Kaplan-Meier curves and Cox regression analyses were used for overall survival (OS) and progression-free survival (PFS) evaluation and comparison between neuroendocrine markers expression status in all melanoma cases or stage I–II cases.

Results

The expression of neuroendocrine markers in melanomas is not uncommon. CgA was positive in 6/304 (2.0%) cases, Syn in 26/304 (8.6%), and CD56 in 56/189 (29.6%). None of the cases co-expressed all the three markers. Focal or weak expression of at least one neuroendocrine marker was identified in 70/188 (37.2%) cases. The expression of CgA was correlated with age (p = 0.019), while the positive expression of Syn and CD56 showed borderline significance (p = 0.078 and 0.083, respectively), but not for any neuroendocrine marker expression. The expression of any neuroendocrine marker showed borderline significance with staging (p = 0.066). The expression of CgA, Syn, CD56, or any neuroendocrine marker did not correlate with clinicopathological features including sex, specimen type, origin, location, and histology subtype. Survival analyses revealed that the expression of neuroendocrine markers was not associated with OS or PFS.

Conclusions

Our study confirms that neuroendocrine marker expression is a common phenomenon in melanomas, but it has no prognostic significance. Nevertheless, awareness can avoid misdiagnosis in cases of melanomas with unusual morphology and immunophenotypes.

Balch CM, Gershenwald JE, Soong SJ, et al. Final version of 2009 AJCC melanoma staging and classification. J Clin Oncol. 2009;27(36):6199–206. https://doi.org/10.1200/jco.2009.23.4799 [published Online First: 2009/11/18].CrossRefPubMedPubMedCentral

Lee H, Torres FX, McLean SA, et al. Immunophenotypic heterogeneity of primary sinonasal melanoma with aberrant expression of neuroendocrine markers and calponin. Appl Immunohistochem Mol Morphol. 2011;19(1):48–53. https://doi.org/10.1097/PAI.0b013e3181ee8dcb.CrossRefPubMed

Shinohara MM, Deubner H, Argenyi ZB. S100, HMB-45, and Melan-a negative primary melanoma. Dermatol Online J. 2009;15(9):7.CrossRef

Agaimy A, Specht K, Stoehr R, Lorey T, Märkl B, Niedobitek G, et al. Metastatic malignant melanoma with complete loss of differentiation markers (undifferentiated/dedifferentiated melanoma): analysis of 14 patients emphasizing phenotypic plasticity and the value of molecular testing as surrogate diagnostic marker. Am J Surg Pathol. 2016;40(2):181–91. https://doi.org/10.1097/PAS.0000000000000527.CrossRefPubMed

Romano R, Carter J, Folpe A. Aberrant intermediate filament and synaptophysin expression is a frequent event in malignant melanoma: an immunohistochemical study of 73 cases. Modern Pathol. 2015;28(8):1033–42. https://doi.org/10.1038/modpathol.2015.62.CrossRef

Xu X, Palsgrove D, Kurian E, Yan S, Oliai BR, Bishop JA. Variable Expression of S100 Protein in Sinonasal Malignant Mucosal Melanoma: A Potential Diagnostic Pitfall. Head Neck Pathol. 2020;14(4):929–35. https://doi.org/10.1007/s12105-020-01158-8.CrossRefPubMedPubMedCentral

Ul-Mulk J, Rasmussen H, Breiting L, et al. A case of collision tumor or transdifferentiation between malignant melanoma and leiomyosarcoma. Indian J Pathol Microbiol. 2012;55(4):538–9. https://doi.org/10.4103/0377-4929.107806 [published Online First: 2013/03/05].CrossRefPubMed

Gattenlöhner S, Brocker E, Muller-Hermelink H. Malignant melanoma with metastatic rhabdomyosarcomatoid transdifferentiation. N Engl J Med. 2008;358(6):649–50. https://doi.org/10.1056/NEJMc0707079.CrossRefPubMed

Banerjee SS, Eyden B. Divergent differentiation in malignant melanomas: a review. Histopathology. 2008;52(2):119–29. https://doi.org/10.1111/j.1365-2559.2007.02823.x.CrossRefPubMed

10.

Juhlin C, Zedenius J, Haglund F. Metastatic malignant melanoma with neuroendocrine differentiation: a case report and review of the literature. J Med Case Rep. 2020;14(1):44. https://doi.org/10.1186/s13256-020-02367-z.CrossRefPubMedPubMedCentral

11.

Ilardi G, Caroppo D, Varricchio S, Vita G, di Lorenzo P, Insabato L, et al. Anal melanoma with neuroendocrine differentiation: report of a case. Int J Surg Pathol. 2015;23(4):329–32. https://doi.org/10.1177/1066896915573568.CrossRefPubMed

12.

Steppert C, Krugmann J, Sterlacci W. Simultaneous endocrine expression and loss of melanoma markers in malignant melanoma metastases, a retrospective analysis. Pathol Oncol Res. 2020;26(3):1777–9. https://doi.org/10.1007/s12253-019-00761-7.CrossRefPubMed

13.

Espinosa I, De Leo A, D'Angelo E, et al. Dedifferentiated endometrial carcinomas with neuroendocrine features: a clinicopathologic, immunohistochemical, and molecular genetic study. Hum Pathol. 2018;72:100–6. https://doi.org/10.1016/j.humpath.2017.11.006.CrossRefPubMed

14.

Bahrami A, Gown A, Baird G, et al. Aberrant expression of epithelial and neuroendocrine markers in alveolar rhabdomyosarcoma: a potentially serious diagnostic pitfall. Modern Pathol. 2008;21(7):795–806. https://doi.org/10.1038/modpathol.2008.86.CrossRef

15.

Kardoust Parizi M, Iwata T, Kimura S, et al. Focal neuroendocrine differentiation of conventional prostate adenocarcinoma as a prognostic factor after radical prostatectomy: a systematic review and meta-analysis. Int J Mol Sci. 2019;20(6). https://doi.org/10.3390/ijms20061374.

16.

Herold Z, Dank M, Herold M, et al. Histopathological chromogranin A-positivity is associated with right-sided colorectal cancers and worse prognosis. Cancers (Basel). 2020;13(1). https://doi.org/10.3390/cancers13010067 [published Online First: 2021/01/02].

17.

Schadendorf D, van Akkooi ACJ, Berking C, et al. Melanoma. Lancet. 2018;392(10151):971–84. https://doi.org/10.1016/s0140-6736(18)31559-9 [published Online First: 2018/09/22].CrossRefPubMed

18.

Banerjee SS, Harris M. Morphological and immunophenotypic variations in malignant melanoma. Histopathology. 2000;36(5):387–402. https://doi.org/10.1046/j.1365-2559.2000.00894.x [published Online First: 2000/05/03].CrossRefPubMed

19.

Kaur K, Kakkar A, Rastogi S, Sharma MC. Sinonasal amelanotic melanoma with neuroendocrine differentiation: a diagnostic conundrum. Ultrastruct Pathol. 2020;44(2):249–54. https://doi.org/10.1080/01913123.2020.1740367.CrossRefPubMed

20.

Pilozzi E, Cacchi C, Di Napoli A, et al. Primary malignant tumour of the lung with neuroendocrine and melanoma differentiation. Virchows Arch. 2011;459(2):239–43. https://doi.org/10.1007/s00428-011-1109-7.CrossRefPubMed

21.

Eyden B, Pandit D, Banerjee SS. Malignant melanoma with neuroendocrine differentiation: clinical, histological, immunohistochemical and ultrastructural features of three cases. Histopathology. 2005;47(4):402–9. https://doi.org/10.1111/j.1365-2559.2005.02240.x.CrossRefPubMed

22.

Gulubova M, Vlaykova T. Chromogranin A-, serotonin-, synaptophysin- and vascular endothelial growth factor-positive endocrine cells and the prognosis of colorectal cancer: an immunohistochemical and ultrastructural study. J Gastroenterol Hepatol. 2008;23(10):1574–85. https://doi.org/10.1111/j.1440-1746.2008.05560.x [published Online First: 2008/09/06].CrossRefPubMed

23.

Kaufmann O, Georgi T, Dietel M. Utility of 123C3 monoclonal antibody against CD56 (NCAM) for the diagnosis of small cell carcinomas on paraffin sections. Hum Pathol. 1997;28(12):1373–8. https://doi.org/10.1016/s0046-8177(97)90226-4 [published Online First: 1998/01/07].CrossRefPubMed

24.

Madahian S, Judelson R, Zhu X, et al. CD56 expression in basaloid anal squamous cell carcinoma - A potential diagnostic pitfall. Ann Diagn Pathol. 2021;53:151758. https://doi.org/10.1016/j.anndiagpath.2021.151758 [published Online First: 2021/05/15].CrossRefPubMed

25.

Kriegsmann K, Zgorzelski C, Muley T, et al. Role of Synaptophysin, Chromogranin and CD56 in adenocarcinoma and squamous cell carcinoma of the lung lacking morphological features of neuroendocrine differentiation: a retrospective large-scale study on 1170 tissue samples. BMC Cancer. 2021;21(1):486. https://doi.org/10.1186/s12885-021-08140-9 [published Online First: 2021/05/03].CrossRefPubMedPubMedCentral

26.

Tsai WH, Chen TC, Dai SH, et al. Case Report: Ectopic Adrenocortical Carcinoma in the Ovary. Front Endocrinol (Lausanne). 2021;12:662377. https://doi.org/10.3389/fendo.2021.662377 [published Online First: 2021/04/06].CrossRef

27.

Takeda K, Takahashi N-H, Shibahara S. Neuroendocrine functions of melanocytes: beyond the skin-deep melanin maker. Tohoku J Exp Med. 2007;211(3):201–21. https://doi.org/10.1620/tjem.211.201.CrossRefPubMed

28.

Coli A, Giacomini PG, Bigotti G, et al. Aberrant neurofilament protein and synaptophysin expression in malignant melanoma of the nasal cavity. Histopathology. 2004;44(2):193–5. https://doi.org/10.1111/j.1365-2559.2004.01784.x [published Online First: 2004/02/07].CrossRefPubMed

Title: Prognostic significance of the aberrant expression of neuroendocrine markers in melanomas
Authors: Yan Wu
Yumei Lai
Miao Zhang
Zhongwu Li
Publication date: 01-12-2021
Publisher: BioMed Central
Keywords: Melanoma
Melanoma
Published in: Diagnostic Pathology / Issue 1/2021
Electronic ISSN: 1746-1596
DOI: https://doi.org/10.1186/s13000-021-01135-x

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Prognostic significance of the aberrant expression of neuroendocrine markers in melanomas

Abstract

Background

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 1/2021

Lipoprotein glomerulopathy associated with the Osaka/Kurashiki APOE variant: two cases identified in Latin America

Mismatch repair deficiency is associated with specific morphologic features and frequent loss of ARID1A expression in ovarian clear cell carcinoma

Hypoproteinemia predicts disease severity and mortality in COVID-19: a call for action

Danon disease: a case report and literature review

Central mucoepidermoid carcinoma arising directly from a glandular odontogenic cyst of the mandible: a case report

The pathological features of leukemic cells infiltrating the renal interstitium in chronic lymphocytic leukemia/small lymphocytic lymphoma from a large single Chinese center