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Malignant Proliferating Pilar Tumor: Clinicopathologic, Immunohistochemical, and Molecular Study of 17 Cases
Jakob M T Moran1, Mia S DeSimone2, Adrián Mariño-Enríquez2
1Department of Pathology, Massachusetts General Hospital, Harvard Medical School.
Abstract:
Proliferating pilar tumors are rare neoplasms that differentiate toward the outer sheath near the isthmus and can rarely undergo malignant transformation. We performed histopathologic evaluation on 26 benign proliferating pilar tumor (BPPT) and 17 malignant proliferating pilar tumor (MPPT). Ki-67 and p53 immunostains were performed on 13 BPPT and 10 MPPT. Six MPPT cases were successfully analyzed by a next-generation sequencing platform which surveyed exonic DNA sequences of 447 cancer genes and 191 regions across 60 genes for rearrangement detection. Patient demographics and clinical characteristics were similar between the BPPT and MPPT groups. Follow-up data of 16 of 17 MPPT (median, 25 mo) showed metastasis in 1 MPPT. The histologic features associated with MPPT include size >2.5 cm, adjacent desmoplastic stroma, small nests or cords of atypical epithelium in surrounding stroma, irregular infiltration or borders, abnormal keratinization, large hyperchromatic nuclei, prominent nucleoli, severe cytologic atypia, nuclear pleomorphism, necrosis, and increased mitotic figures. MPPT harbors copy number gains of 15q and losses of 6p and 6q, findings previously reported in BPPT. However, MPPT harbors frequent TP53 mutations as molecular markers of progression. Different from cutaneous squamous cell carcinoma, MPPT more frequently demonstrates low tumor mutational burden and typically lacks a UV signature, suggestive of a different etiologic pathway than squamous cell carcinoma. In summary, with a median follow-up of 25 months, this study shows that MPPT is a biologically indolent carcinoma with rare metastasis. Molecular analyses suggest a non-UV-related pathogenesis with frequent TP53 aberration.
Insights
Malignant proliferating pilar tumors (MPPT) are rare and biologically indolent, with infrequent metastasis. Molecular analysis suggests a distinct etiologic pathway from squamous cell carcinoma, often involving TP53 mutations.
Area of Science:
- Dermatopathology
- Oncology
- Molecular Pathology
Background:
- Proliferating pilar tumors (BPPT) are rare neoplasms with potential for malignant transformation.
- Malignant proliferating pilar tumors (MPPT) represent a rare but significant subset.
- Understanding the distinct molecular and histopathologic features of MPPT is crucial for accurate diagnosis and prognosis.
Purpose of the Study:
- To compare the histopathologic and molecular features of benign proliferating pilar tumors (BPPT) and malignant proliferating pilar tumors (MPPT).
- To identify key histologic and molecular markers associated with malignant transformation and progression in proliferating pilar tumors.
- To investigate the potential etiologic pathways of MPPT, differentiating them from cutaneous squamous cell carcinoma.
Main Methods:
- Histopathologic evaluation of 26 BPPT and 17 MPPT cases.
- Immunohistochemical analysis using Ki-67 and p53.
- Next-generation sequencing of 447 cancer genes and 191 rearrangement regions in 6 MPPT cases.
Main Results:
- MPPT exhibited specific histologic features including larger size, desmoplastic stroma, irregular infiltration, and cytologic atypia.
- Copy number gains of 15q and losses of 6p/6q were observed in MPPT, consistent with findings in BPPT.
- Frequent TP53 mutations were identified in MPPT, alongside a low tumor mutational burden and lack of UV signature, suggesting a unique pathogenesis.
Conclusions:
- Malignant proliferating pilar tumors are biologically indolent with a low metastatic potential, despite malignant cytologic features.
- TP53 mutations serve as key molecular markers for progression from benign to malignant proliferating pilar tumors.
- The distinct molecular profile of MPPT suggests an etiology independent of UV radiation, differing from cutaneous squamous cell carcinoma.
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