Pilomatrixoma (PMX) (pilomatricoma)
- Some irregular and crowded clusters of basaloid cells are seen, with abrupt areas of pale pink ghost cells.
- Most basaloid cells are uniform and small in size with smooth nuclear border. Some areas of basaloid cells show mild enlarged nuclei with fine chromatin pattern and tiny nucleoli and scant delicate ill-defined cytoplasm, but without apoptosis and mitotic activity. Few basaloid cells are scattered in the background.
- Anucleated squamous cells show pale pink cytoplasm only (Ghost cells), some are well demarcated border and some are mix-up with basaloid cells.
- Some atypical cells show dark hyperchromatic nuclei and angulated/crushed appearance with eosinophilic cytoplasmic background, arranged loose cluster. (such areas resembles squamous cell carcinoma in present case, however, paying attention to ghost cells without any necrotic or apoptotic and mitotic activity as well as slow growing dermal/subcutaneous tumor prevent the misinterpretation as a squamous cell carcinoma)
- Few large multinucleated histiocytic giant cell, scanty inflammatory cells are seen in some dirty background; however, calcified debris are not seen. Occasional histiocytic granuloma is seen.
Practical Points of Pathoclinics:
- Pilomatrixoma/Pilomatricoma (calcified epithelioma of Malherbe) is an uncommon benign appandageal skin tumour of hair follicle matrix.
- Children and young adults with head and neck region or upper extremities slow growing, firm to hard, deep dermal or cutaneous swelling, of around 2-3 cm size is the common clinical presentation. Overlying skin remains unremarkable in most cases. Females are more commonly affected. Clinically variety of benign and malignant tumours fall in the differential diagnosis of pilomatricoma and so commonly misdiagnosed.
- Histologically, pilomatricoma is a well circumscribed tumour. Presence of two types of cell populations (basaloid cells and anucleated ghost/squamous cells) are helpful and necessary diagnostic features.
- Type of aspirate in pilomatricoma is often cheese-like thick whitish aspirate. Well sampled cytology smears are often mirror image of histology section. Important diagnostic cytological features of pilomatricoma are presence of both basaloid cells and ghost/anucleated squames cells. Basaloid cells are arranged as single cells, loose clusters as well as crowded cohesive irregular clusters. Usually, basaloid cells are small uniform with regular round to oval nuclei. Chromatin pattern is finely granular with prominent nucleoli. Cytoplasm is scanty and ill-defined. Variable numbers of naked basaloid nuclei are present in the background of most cases. Anucleated squames/ghost cells are appears in clumps or scattered fragmented single cells. Other supportive features are multinucleated giant cells, inflammatory cells, nucleated squamous cells, and calcium debris in a dirty background. Moderate nuclear pleomorphism and a mitotic figure can be seen. Atypical cells arranged in a whorled cluster resembling squamous cell carcinoma is a major pitfall.
- The differential diagnosis includes epidermal inclusion cyst, trichilemmal cyst, branchial cleft cyst, foreign body reaction, squamous cell carcinoma, mucoepidermoid carcinoma, and Merkel cell carcinoma.
- Epidermal inclusion cyst commonly shows mature squamous cells and keratinous debris. Calcified material is not common. Basal cells are almost never seen. Sometimes, secondary infection may induce giant cells reaction in surrounding tissue.
- Significant proportion of crowded clusters as well as single basaloid cells with mildly irregular hyperchromatic nuclei along with occasional mitotic figures, with very scant or sometimes overlooking of tiny areas of ghost cells may create confusion with malignant tumour like basal cell carcinoma or basaloid squamous cell carcinoma or small cell neuroendocrine carcinoma/Merkel cell carcinoma.
- Atypical cells in a whorled fashion with dirty keratinized ghost cells debris mimic squamous cell carcinoma.
- Dirty granular debris with large histiocytic cells and ghost squamoid cells may resemble to low grade mucoepidermoid carcinoma.
- Granular calcified debris and histiocytic multinucleated giant cells are supportive features for pilomatricoma and not of much diagnostic help.
- Careful search for ghost cells along with basaloid cells is important to prevent misdiagnosis as a malignant tumour, as basaloid cells are commonly overrepresented in the cytology smears. However, we pathologists are clinician first so, careful consideration of clinical presentation including age, location and size prevent the diagnostic accidents. Malignant tumours have relatively rapid growth rate than pilomatricoma, while later is a slow growing relative long-standing lesion.
- Primary/Metastatic carcinoma shows significant nuclear pleomorphism, tumour necrosis and frequent mitoses. Metastatic tumour has a known history of primary in most of the cases.
- Malignant pilomatrixoma show striking cytologic atypia, increased number of squamous and basaloid cells, necrosis and frequent mitotic figures.
- Pilomatricoma is usually a single lesion. However, few patients present with more than one lesion. Multiple pilomatricoma need to be investigated for other disease and syndromic associations. Pilomatrixomas are associated with mutation of Wnt pathway and so several genetic conditions like colon cancer or familial associated polyposis (FAP-related syndrome). The presence of six or more pilomatricomas are highly suggestive of an underlying syndrome, like Steinert myotonic dystrophy, familial adenomatous polyposis-related syndromes (including Gardner syndrome), Turner syndrome, or Rubinstein-Taybi syndrome. Some reports also mentioned about the associated anomalies in childhood pilomatricomas. Some cases of pilomatricomas are also associated with gliomatosis cerebri and seminoma.
- In difficult cases, a specific diagnosis of pilomatricoma by FNAC may not possible. In such instances, impression of basaloid cells rich lesion with close relevant differentials can be given with advised of excision and frozen section study as per clinical situation. Frozen section study also helps in the diagnosis during excision and guide the extent of surgery. Complete surgical excision with clear margins is almost always curative.
Jones CD, Ho W, Robertson BF, Gunn E, Morley S. Pilomatrixoma: A Comprehensive Review of the Literature. Am J Dermatopathol. 2018 Sep;40(9):631-641. doi: 10.1097/DAD.0000000000001118. PMID: 30119102
Ciriacks K, Knabel D, Waite MB. Syndromes associated with multiple pilomatricomas: When should clinicians be concerned? Pediatr Dermatol. 2020 Jan;37(1):9-17. doi: 10.1111/pde.13947. Epub 2019 Oct 16. PMID: 31618803.