Dermatology Online Journal

Pilomatrical carcinoma: A case in a patient with HIV and hepatitis C

Dermatology Online Journal 14 (1): 4

Columbia University Department of Dermatology

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Abstract

Pilomatrical carcinoma is a rare tumor without a single pathognemonic feature that distinguishes it from the benign pilomatricoma. We report a 51-year-old man with HIV, hepatitis C, and pilomatrical carcinoma.

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The classic features of a benign pilomatricoma—pleomorphic basaloid cells accompanied by central areas with keratotic material, shadow or ghost cells, and zones of necrosis with surrounding stromal desmoplasia—suggest a carcinoma rather than a benign neoplasm. Pilomatrical carcinoma shows more fulminant and exuberant features that include asymmetry, poor circumscription, large and variably-shaped aggregations of pleomorphic basaloid cells, basaloid cells with vesicular nuclei and prominent nucleoli, atypical mitotic figures, very extensive areas of necrosis en masse, ulceration, and infiltrative growth patterns. No single feature is diagnositic of pilomatrical carcinoma and immunohistochemistry does not distinguish benign from malignant pilomatrical neoplasia. Pilomatricomal carcinoma has been most often treated with wide surgical excision, although Mohs micrographic surgery has been reported effective. Radiation therapy may have a role in the palliation of metastatic pilomatrical carcinoma, which is usually fatal.

Clinical synopsis

A 51-year-old man with HIV since 1986, CD4 count of 84, and hepatitis C with hepatic cirrhosis, presented with a 4-cm firm, purple nodule on the posterolateral aspect of his left upper extremity adjacent to the triceps muscle (Fig. 1). The nodule first appeared 9 months earlier and had been growing slowly but progressively. A CT examination of the left arm showed a clear flat plane between the mass and arm musculature.

Figure 1	Figure 2
Figure 1. Purplish nodule of pilomatrical carcinoma 4 cm in diameter on forearm Figure 2. Large and variably-shaped aggregations of pleomorphic basaloid cells with vesicular nuclei and prominent nucleoli (H&E, original magnification x40).

Histopathological examination of a biopsy specimen revealed large, irregular- shaped nests of basophilic matrical cells with abundant mitotic figures and surrounding necrosis (Figs. 2-4). This was diagnosed as pilomatrical carcinoma. The patient returned to have the tumor removed 4 months after the biopsy, by which time the tumor had grown to 7 cm. It was excised with a 1 cm margin and histological sections demonstrated that the carcinoma had been removed in its entirety. Approximately 4 months later, the patient died unexpectedly in his home from a variceal hemorrhage of the esophagus. An autopsy was performed and revealed no recurrence of the pilomatrical carcinoma at the excision site and no visceral metastases. No specific cause of death was identified other than cardiovascular collapse due to the variceal hemorrhage attributed to hepatitis C.

Figure 3	Figure 4
Figure 3. Extensive areas of necrosis en masse, pleomorphic basaloid cells (H&E, original magnification x100) Figure 4. Extensive areas of necrosis en masse, pleomorphic basaloid cells (H&E, original magnification x400)

Discussion

A pilomatricoma (PM) with aggressive behavior was noted as early as 1927, but it was not until 1980 when well-defined histopathologic criteria for the entity known alternatively as pilomatrical carcinoma (PC), malignant pilomatricoma, pilomatrix carcinoma, or calcifying epitheliocarcinoma of Malherbe were put forth by Lopansri and Mihm [1]. A variant of pilomatricoma in the elderly that has a predominance of basoloid cells has been described as a proliferating pilomatricoma (PP) and resembles pilomatrical carcinoma. Proliferating pilomatricomas, however, have not been reported to metastasize or result in death [2]. We report the first pilomatrical carcinoma in a patient with HIV.

Most PCs occur on the head and neck [3]. However, pilomatrical carcinomas have been reported to manifest on areas that include the right knee [4], the axilla [5], the chest [6], the inguinal region [7] and the arm [8] as in this case.

The epidemiology of pilomatrical carcinoma has been defined and is different from pilomatricomas [9, 10, 11, 12]. Pilomatricomas are seen more often in females (3:1 female:male ratio) whereas PCs are seen in the opposite ratio (3:1 male:female) [9, 10, 11]. Pilomatricomas usually occur in children, but pilomatrical carcinomas usually occur in middle aged or elderly adults. The average age of patients diagnosed with PM is 8.7 years (range 8 months to 19 years), whereas the average age of diagnosis for PC is 45 years (range 8 - 88 years) [9]. The age range of the reported cases with distant metastases is 31 to 74 years [9]. About 90 cases of PC and 9 cases of metastatic PC have been reported.

Figure 5	Figure 6
Figure 5. Cells demonstrating nodular and invasive growth patterns (H&E, original magnification x100) Figure 6. Pleomorphic cells (H&E, original magnification x400)

Reports note that PC often appears to arise in long-standing and stable PMs [4, 9, 10, 11, 12]. Pilomatrical carcinomas usually range from 1 to 3 cm [13], although PCs as large as 10 cm have been reported. A review of the clinical images from articles illustrating PC shows that they are usually red with yellow, white, and tan areas. A Canadian report noted that a PM turned purple as it grew rapidly (the authors did not note a PC in this case); no report appears to note that PC can possess a purple hue [11]. Some authors suggest that a PC is most commonly mistaken for a sebaceous cyst but based on a review of the images of PC, they usually seem to resemble calcified cysts (sometimes multiloculated) with an intensely erythematous surface and halo.

Immunohistochemistry studies have not yielded markers or patterns of markers that consistently and definitively distinguish pilomatricomas from PC. In a series of 15 pilomatrical carcinomas and 13 benign pilomatricomas [14], β-catenin expression was assessed using immunohistochemistry and DNA sequencing of exon 3 from CTNNB1 (the defect that leads to the development of pilomatricoma). All cases showed nuclear localization of β-catenin, mutations in exon 3, and expression of nuclear cyclin D1. Two pilomatrical carcinomas showed significant nuclear accumulation of p53, which was absent in all benign pilomatricomas. Similarly, in a study of 21 pilomatricomas and 5 pilomatrical carcinomas, all 26 tumors displayed both nuclear and cytoplasmic presence of the β-catenin gene mutation, but no staining of shadow cells [15].

Differentiating pilomatricoma and pilomatrical carcinoma relies on histological examination of H&E stained tissue. Pilomatricoma displays features that in other contexts would suggest malignancy (pleomorphic basaloid cells accompanied by central areas with keratotic material, shadow or so called ghost cells, and zones of necrosis with surrounding stromal desmoplasia) [16]. Histologically, a pilomatrical carcinoma is an exaggeration of a pilomatricoma. Pilomatrical carcinoma exhibits extensive asymmetry, poor circumscription, large and variably-shaped aggregations of pleomorphic basaloid cells with vesicular nuclei and prominent nucleoli, frequent atypical mitotic figures, extensive areas of necrosis en masse, infiltrative growth pattern, and sometimes ulceration [1, 6]. The diagnosis of pilomatrical carcinoma remains based on the morphology of histopathological features evaluated in toto [1, 6].

PC must be treated with care. PCs commonly recur after standard excision and can grow rapidly in size. In rare cases, pilomatrical carcinoma can metastasize; metastatic PC causes death in almost all cases. The most widely reported treatment of PC (and the apparent standard of care) is wide surgical excision [9, 10, 11, 12], but Mohs micrographic surgery has been reported to be effective [17]. Radiation and chemotherapy have been used with mixed effect for palliation of metastatic PC [18, 19, 20, 21].

Conclusion

Pilomatrical carcinoma sometimes may arise in a preexisting pilomatricoma that possesses a completely benign clinical appearance. Rapidly growing pilomatricomas or nodules that appear to be inflamed calcified cysts should prompt complete excision. Because the histology of PC and PM is similar, it might be difficult to make the correct diagnosis if only a small biopsy is taken. Luckily, PC is an extremely rare entity. Although it possesses a propensity for local recurrence, it metastasizes in only about 10 percent of cases. When PC is metastatic, however, mortality approaches 100 percent. As the eye sees what the mind knows, knowing that pilomatricomas can undergo malignant transformation is the first step in diagnosing and treating patients with PC.

Acknowledgment: The author wishes to acknowledge the help of Boaz Kurtis MD in assembling material related to the preparation of this article.

References

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