Undifferentiated pleomorphic sarcoma of the breast with neoplastic fever: case report and genomic characterization

Abstract

Purpose: Primary breast sarcomas are extraordinary rare, in particular undifferentiated pleomorphic sarcoma (UPS). UPS with neoplastic fever (UPS-NF) of the breast has not been reported yet. Here, we present an extended UPS-NF of the breast including its comprehensive molecular workup.

Methods: A 58-year-old female presented with general malaise, fever spikes, weight loss, and a massively swollen left breast. C-reactive protein and blood leucocytes were significantly increased. However, repeated blood cultures and smears were all sterile. Histopathology of the abscess-forming tumor revealed an undifferentiated malignancy with numerous of tumor giant cells as well as spindle-shaped cells with nuclear pleomorphism and hyperchromasia. Immunohistochemistry demonstrated partial, patchy desmin staining and weak heterogonous neuron-specific enolase immunoreactivity of tumor cells, but a focal staining for Melan-A.

Results: Neither common melanoma driver mutations nor an ultraviolet mutational signature was detected by whole genome sequencing. Using FISH and RT-PCR we also excluded translocations characteristic for clear cell sarcoma. Thus, the diagnosis of inflammatory UPS-NF of the breast was considered highly probable. Despite a complete mastectomy, the tumor recurred after only three months. This recurrence was treated with a combination of ipilimumab and nivolumab based on the primary tumor's TPS score for PD-L1 of 30%. After an initial response, however, the tumor was progressive again.

Conclusion: We describe here the first case of UPS-NF of the breast, which shows great clinical and histopathologic resemblances to previously reported UPS-NF of other anatomic localizations.

Keywords: Breast cancer; High grade sarcoma; Neoplastic fever; Undifferentiated pleomorphic sarcoma.

Fig. 1

Showing a massively swollen left breast with violaceous erythema, venectases, shiny thinned skin, and necrosis of the nipple in a patient with undifferentiated pleomorphic sarcoma accompanied by neoplastic fever (UPS-NF, a). Histologic examination of the completely excised breast tumor revealed a high-grade sarcoma composed of numerous tumor giant cells and atypical spindle-shaped tumor cells (× 40, b; × 100, c). Computed tomography image demonstrating a huge, partly necrotic tumor of the left breast in a patient with UPS-NF (d)

Fig. 2

Mutational analysis shows medium tumor mutational burden and absence of UV-associated characteristics. (a) Variants per megabasepair (Mbp) colored by nonsynonymous (red shades) and synonymous mutations. (b) Fraction of variants colored by transitions and transversions. (c) Fraction of variants by transition and transversions broken down by trinucleotide context (x axis) and colors by mutation type. Relative contribution of single base substitution (SBS) signatures after fitting trinucleotide context frequency to reference mutational signatures from COSMIC v3.1 database

Fig. 3

Showing a patient with a massive relapse of an undifferentiated pleomorphic sarcoma of the breast (a). Three cycles of combined immunotherapy and radiotherapy resulted in significant regression of the tumor masses (b)