Basal Cell Carcinosarcoma With PTCH1 Mutations in Both Epithelial and Sarcomatoid Primary Tumor Components and in the Sarcomatoid Metastasis

Abstract

Basal cell carcinosarcoma is a rare biphenotypic malignant skin tumor, in which one tumor component has light microscopic features of basal cell carcinoma, whereas the other has features of sarcoma. Clinical experience with this tumor is limited, and associated molecular genetic alterations are unknown. Herein, we report a unique case of metastatic basal cell carcinosarcoma, in which we analyzed the 2 components of the primary tumor as well as the metastasis by next-generation sequencing. The patient was a 72-year-old man who presented with a 7-year history of a large tumor of the left forearm. The tumor showed mixed features of basal cell carcinoma and undifferentiated sarcoma. The patient underwent a wide local excision and sentinel lymph node biopsy, which revealed microscopic subcapsular deposits of metastatic sarcomatoid tumor. One year later, intra-abdominal metastatic tumor was detected and resected. It had sarcomatoid features by light microscopy and failed to stain for epithelial markers by immunohistochemistry. DNA was extracted separately from the epithelial and sarcomatoid component of the primary tumor, intra-abdominal metastasis, and normal tissue. All exons of 230 cancer-associated genes were sequenced to an average read depth of >500-fold. This revealed multiple identical mutations in epithelial and sarcomatoid tumor compartments. Both compartments harbored 2 identical mutations, a truncating and a missense mutation, in the patched gene (PTCH1). This finding is not only of interest for a shared heritage of different subpopulations in a biphenotypic tumor, but also relevant clinically. It provides a rationale for the clinical use of hedgehog pathway inhibitors for treatment of patients affected by this tumor. Unfortunately, the patient reported herein died of metastatic disease before targeted therapy could be initiated.

Squamous cell carcinoma with osteoclast‐like giant cells: a morphologically heterologous group including carcinosarcoma and squamous cell carcinoma with stromal changes

“…Mutational analysis by Paniz‐Mondolfi et al confirmed that both elements of cutaneous carcinosarcoma had identical mutations . In addition, Kiuru et al showed that basal cell carcinosarcoma shared identical PTCH1 mutations in both epithelial and sarcomatoid primary tumor components and in the sarcomatoid intraabdominal metastatic tumor . Recently, Harms et al reported that three of four basal cell carcinosarcoma displayed a similar copy number variations and copy‐neutral loss of heterozygosity changes between the epithelial and mesenchymal components within each tumor …”

The history of dermatology, venereology and dermatopathology in different countries - China

“…This was highlighted in recent work by Siroy et al Their study of 699 advanced-stage melanomas found significant associations of mutations with clinical subtypes and primary tumor location [53]. Indeed, the authors showed that BRAF V600E mutations were significantly associated with cutaneous and unknown primary melanomas (p<0.001), whereas KIT mutations were significantly associated with acral and mucosal melanomas (p<0.001) [53].…”

“…Indeed, the authors showed that BRAF V600E mutations were significantly associated with cutaneous and unknown primary melanomas (p<0.001), whereas KIT mutations were significantly associated with acral and mucosal melanomas (p<0.001) [53]. Additionally, BRAF V600E mutations were significantly associated with the trunk location compared with head and neck (p=0.0004), whereas TP53 mutations were significantly associated with head and neck compared with the trunk or extremities (p=0.03 and p<0.0001, respectively) [53].…”

Syringocystadenocarcinoma papilliferum associated with atypical stroma: A hitherto undocumented variant of sarcomatoid carcinoma

“…the “conversion theory” suggests that the malignant mesenchymal component derives from the malignant epithelial component during the evolution of the neoplasm . Although different authors have favored different theories, nowadays clearly polarized toward the underlying shared monoclonality, we believe that the histogenetic mechanisms should be better hypothesized depending on each individual case …”