March 2023 – Breast Pathology Case 1

Dermatofibrosarcoma protuberans.

The histologic sections in this case confirm a monomorphic spindle cell proliferation with a storiform architecture. While submitted as a “breast biopsy,” the lesion is centered in the subcutis, and no breast epithelium proper is present. The nuclei are uniform with minimal cytologic atypia, and mitotic activity is low. Infiltration and entrapment of adipose tissue in a honeycombing pattern is well-demonstrated. 

By immunohistochemistry (IHC), the neoplastic cells are diffusely positive with CD34, while negative with STAT6. The overall morphology and immunophenotype are most consistent with dermatofibrosarcoma protuberans (DFSP).

DFSP is an uncommon and locally aggressive neoplasm that is most commonly encountered in the dermis and subcutaneous tissues of the skin. Rarely, DFSP may present as a deeper-seated lesion. It is characterized by diffuse infiltration with a honeycombing pattern of entrapment of adipose tissue. The neoplastic cells are uniform with plump to elongated nuclei and with a whorled storiform histoarchitecture.^1,2 Fibrosarcomatous differentiation can infrequently occur, with a more nodular and fascicular appearance of cells with cytologic atypia and increased mitotic activity.³

By IHC, DFSP is strongly and diffusely positive for CD34, a reliably sensitive but not specific marker.² It is most frequently characterized by a t(17;22)(q22;q13) COL1A1-PDGFB fusion. Rare cases may be negative for PDGFB rearrangements by fluorescence in situ hybridization (FISH), as in this case. They may instead harbor fusions involving PDGFD, which has been observed in some cases of DFSP occurring in the breast.⁴

Primary sarcomas, especially other than phyllodes tumors, of the breast are exceedingly rare, comprising <0.1% of all breast malignancies. Nonetheless, sarcomas may be encountered in both breast biopsies and excisions. Ancillary testing may be necessary to rule out the differential diagnosis of metaplastic (spindle cell) carcinoma. The subcutaneous/dermal location of the lesion in this case, combined with histologic features and IHC results, allowed for a specific diagnosis of DFSP. While locally aggressive and prone to local recurrence (up to 60%), distant metastases from DFSP are rare.^2,3

References

1. Laharwani H, Prakash V, Walley D, Akhtar I. DFSP of the breast: histomorphological, immunohistochemical, and molecular features of a rare case in an unusual location. Appl Immunohistochem Mol Morphol. 2021 Sep 1;29(8):e73-e82. doi:10.1097/PAI.0000000000000935. PMID: 34282067.
2. Hao X, Billings SD, Wu F, Stultz TW, Procop GW, Mirkin G, Vidimos AT. Dermatofibrosarcoma protuberans: update on the diagnosis and treatment. J Clin Med. 2020 Jun 5;9(6):1752. doi:10.3390/jcm9061752. PMID: 32516921; PMCID: PMC7355835.
3. Mentzel T, Beham A, Katenkamp D, Dei Tos AP, Fletcher CD. Fibrosarcomatous ("high-grade") dermatofibrosarcoma protuberans: clinicopathologic and immunohistochemical study of a series of 41 cases with emphasis on prognostic significance. Am J Surg Pathol. 1998 May;22(5):576-87. doi:10.1097/00000478-199805000-00009. PMID: 9591728.
4. Dickson BC, Hornick JL, Fletcher CDM, Demicco EG, Howarth DJ, Swanson D, Zhang L, Sung YS, Antonescu CR. Dermatofibrosarcoma protuberans with a novel COL6A3-PDGFD fusion gene and apparent predilection for breast. Genes Chromosomes Cancer. 2018 Sep;57(9):437-445. doi:10.1002/gcc.22663. Epub 2018 Aug 14. PMID: 30014607; PMCID: PMC6762016.