A rare tumour – metastatic digital papillary adenocarcinoma: literature review, clinical case of successful therapy

Digital papillary adenocarcinoma (DPA ) is a rare malignant neoplasm of sweat glands, which was first described by Helwig in 1979 and then classified by Kao in 1987. This disease most often occurs in men aged 50–70 years and is characterized by a relatively favorable prognosis. In most cases, radical excision of the tumor leads to cure. However, 14–47 % of patients develop distant metastases with predominant lung involvement (70 %). The study of etiology and pathogenesis of this rare cancer and its molecular genetic profile seems to be interesting. Currently, there is no clear approach to the treatment of metastatic DPA , but sporadic cases of using chemotherapy have been reported. Aim of the study: to analyze current data on the pathogenesis of DPA , diagnostic features and treatment methods used, as well as to present the first clinical case of treatment of disseminated digital carcinoma with immune checkpoint inhibitors described in scientific literature. Material and Methods. A search of available literature published in Medline, Pubmed, etc. databases from 1984 to 2023 was performed, 21 sources were included in this review. Clinical Case Description. We present a rare case of metastatic digital papillary carcinoma in a 23-year-old male with disease manifestation at the age of 14 years. Lack of vigilance and awareness of oncologists and morphologists did not allow timely diagnosis of malignancy, even in case of 3 local recurrences of the disease. Only biopsy of a metastatic lung nodule with histological and IHC examination (of archival and new material) made it possible to make a correct diagnosis. This case revealed 2 potential targets that could be used for disease control: androgen receptor positive expression and PD -L1 expression with CPS =20. The use of immune response checkpoint inhibitors (ipilimumab + nivolumab) resulted in partial response followed by stable disease.

1. Helwig E.B. Eccrine acrospiroma. J Cutan Pathol. 1984; 11(5): 415–20. doi: 10.1111/j.1600-0560.1984.tb00398.x.

2. Kao G.F., Helwig E.B., Graham J.H. Aggressive digital papillary adenoma and adenocarcinoma. A clinicopathological study of 57 patients, with histochemical, immunopathological, and ultrastructural observations. J Cutan Pathol. 1987; 14(3): 129–46. doi: 10.1111/j.1600-0560.1987.tb00488.x.

3. Pathology and Genetics of Skin Tumours. WHO Classification of Tumours. Lyon: IARC Press, 2006.

4. Digital papillary adenocarcinoma. WHO Classification of Skin Tumours. Lyon: IARC Press, 2018.

5. Balci M.G., Tayfur M., Deger A.N., Cimen O., Eken H. Aggressive papillary adenocarcinoma on atypical localization: A unique case report. Medicine (Baltimore). 2016; 95(28). doi: 10.1097/MD.0000000000004110.

6. Bartelstein M.K., Schwarzkopf E., Busam K.J., Brady M.S., Athanasian E.A. Sentinel lymph node biopsy predicts systemic recurrence in digital papillary adenocarcinoma. J Surg Oncol. 2020; 122(7): 1323–7. doi: 10.1002/jso.26170.

7. Cascardo C.A., Cornell G., Moesch J.R. Human papillomavirus 42-associated digital papillary adenocarcinoma. JAAD Case Rep. 2022; 32: 52–4. doi: 10.1016/j.jdcr.2022.10.038.

8. Leiendecker L., Neumann T., Jung P.S., Cronin S.M., Steinacker T.L., Schleiffer A., Schutzbier M., Mechtler K., Kervarrec T., Laurent E., Bachiri K., Coyaud E., Murali R., Busam K.J., Itzinger-Monshi B., Kirnbauer R., Cerroni L., Calonje E., Rütten A., Stubenrauch F., Griewank K.G., Wiesner T., Obenauf A.C. Human Papillomavirus 42 Drives Digital Papillary Adenocarcinoma and Elicits a Germ Cell-like Program Conserved in HPVPositive Cancers. Cancer Discov. 2023; 13(1): 70–84. doi: 10.1158/2159-8290.CD-22-0489.

9. Bui C.M., Pukhalskaya T., Smoller B.R., Zengin H.B., Heneidi S., Vail E., Makhoul E., Balzer B. Two distinct pathogenic pathways of digital papillary adenocarcinoma – BRAF mutation or low-risk HPV infection. J Cutan Pathol. 2023; 50(6): 568–76. doi: 10.1111/cup.14386.

10. Rismiller K., Knackstedt T.J. Aggressive Digital Papillary Adenocarcinoma: Population-Based Analysis of Incidence, Demographics, Treatment, and Outcomes. Dermatol Surg. 2018; 44(7): 911–7. doi: 10.1097/DSS.0000000000001483.

11. Duke W.H., Sherrod T.T., Lupton G.P. Aggressive digital papillary adenocarcinoma (aggressive digital papillary adenoma and adenocarcinoma revisited). Am J Surg Pathol. 2000; 24(6): 775–84. doi: 10.1097/00000478-200006000-00002.

12. Suchak R., Wang W.L., Prieto V.G., Ivan D., Lazar A.J., Brenn T., Calonje E. Cutaneous digital papillary adenocarcinoma: a clinicopathologic study of 31 cases of a rare neoplasm with new observations. Am J Surg Pathol. 2012; 36(12): 1883–91. doi: 10.1097/PAS.0b013e31826320ec.

13. Weingertner N., Gressel A., Battistella M., Cribier B. Aggressive digital papillary adenocarcinoma: A clinicopathological study of 19 cases. J Am Acad Dermatol. 2017; 77(3): 549–58. doi: 10.1016/j.jaad.2017.02.028.

14. Kobayashi T., Hiura A., Oishi K., Maeda S., Le Pavoux A.J., Ohara K., Uruga H. Aggressive Digital Papillary Adenocarcinoma With Multiple Organ Metastases: A Case Report and Review of the Literature. Am J Dermatopathol. 2016; 38(12): 910–4. doi: 10.1097/DAD.0000000000000703.

15. Vanderbilt C., Brenn T., Moy A.P., Harloe G., Ariyan C., Athanasian E., Busam K.J. Association of HPV42 with digital papillary adenocarcinoma and the use of in situ hybridization for its distinction from acral hidradenoma and diagnosis at non-acral sites. Mod Pathol. 2022; 35(10): 1405–10. doi: 10.1038/s41379-022-01094-8.

16. Trager M.H., Jurkiewicz M., Khan S., Niedt G.W., Geskin L.J., Carvajal R.D. A Case Report of Papillary Digital Adenocarcinoma With BRAFV600E Mutation and Quantified Mutational Burden. Am J Dermatopathol. 2021; 43(1): 57–9. doi: 10.1097/DAD.0000000000001694.

17. Surowy H.M., Giesen A.K., Otte J., Büttner R., Falkenstein D., Friedl H., Meier F., Petzsch P., Wachtmeister T., Westphal D., Wieczorek D., Wruck W., Adjaye J., Rütten A., Redler S. Gene expression profiling in aggressive digital papillary adenocarcinoma sheds light on the architecture of a rare sweat gland carcinoma. Br J Dermatol. 2019; 180(5): 1150–60. doi: 10.1111/bjd.17446.

18. Feldmeyer L., Prieto V.G., Ivan D., Nagarajan P., Tetzlaff M.T., Curry J.L., Bell1 D., Moon B.S., Torres-Cabala C.A., Aung P.P. Role of radiotherapy in aggressive digital papillary adenocarcinoma. Annals of Clinical and Laboratory Science. 2016; 46(2): 222–4.

19. Gorva A.D., Mohil R., Srinivasan M.S.Aggressive digital papillary adenocarcinoma presenting as a paronychia of the finger. J Hand Surg Br. 2005; 30(5): 534. doi: 10.1016/j.jhsb.2005.01.011.

20. Frey J., Shimek C., Woodmansee C., Myers E., Greer S., Liman A., Adelman C., Rasberry R. Aggressive digital papillary adenocarcinoma: a report of two diseases and review of the literature. J Am Acad Dermatol. 2009; 60(2): 331–9. doi: 10.1016/j.jaad.2008.07.038.

21. Bakotic B., Antonescu C.R. Aggressive digital papillary adenocarcinoma of the foot: the clinicopathologic features of two cases. J Foot Ankle Surg. 2000; 39(6): 402–5.