—  SPECIALTY CONFERENCE  —

Cytopathology

Case 1 - Pilomatrixoma

Martha Bishop Pitman
Harvard Medical School and Massachusetts General Hospital
Boston, MA


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Clinical History
A 52 year female presents with a 1 month history of a deep cyst in the left cheek. The cyst was anterior to the parotid gland and not associated with the salivary duct. The clinical impression was a sebaceous cyst. An FNAB was performed.

Cytology:
The smear background is filled with blood tinged inflammatory cyst debris with clusters of epithelioid histiocytes and rare scattered multinucleated giant cells. Within this debris are several large and a few smaller cellular tightly to loosely cohesive clusters of small uniform basaloid cells; single basaloid cells are also seen in the cyst debris. Even though visualization of cellular detail is obscured in many groups due to blood and cyst fluid, the overall monotony of these basaloid cells is apparent. There is no pleomorphism, prominent nuclear molding, cellular necrosis or mitotic activity. The nuclei of the cells are round to oval with a consistently even chromatin pattern and occasional prominent nucleoli. The cytoplasm is scant, delicate and ill-defined. Subtly present within the cyst debris are widely scattered degenerated squamous cells, most with no nuclear preservation ("ghost cells"). Pertinent negative findings: no viable anucleated squames, no oncocytes, no mucinous cells or background mucin and no myxoid or fibrillar stroma/globules and no true cellular necrosis.

Cytological Diagnosis: Pilomatrixoma

Histological Diagnosis: same

Discussion:
Pilomatrixoma (PMX), also know as calcifying epithelioma of Malherbe, is a rare benign skin neoplasm arising from the hair matrix. The typical presentation is that of a solitary, superficial, hard, slow growing deep dermal nodule most commonly on the head, neck and upper extremities of children and young adults. These tumors can occur at any age, however, and may have an unusual clinical presentation such as multicentricity, large size and deep location adding to the clinical diagnostic difficulty. As in this case, the clinical diagnosis is frequently incorrect, 84% in one study (Wang, et. al.), with sebaceous cyst being a common clinical misdiagnosis.

Although the histological features of the tumor are quite characteristic and readily recognized by the presence of a well demarcated basaloid tumor with squamoid features and central degeneration including ghost squamous cells, the cytological features are less recognized. Aspiration smears are commonly misdiagnosed as both benign and malignant neoplasms, the latter having potentially serious patient management implications.

The cytological features of PMX are limited to about 100 cases, most as single case reports and small series. The largest series of 22 cases was recently published in Diag. Cytopathol. last year (Wang, et.al.). The two key features found in this series, not suprisingly, were basaloid cells and ghost cells. As in our case, the basaloid cells were described as uniform, small (about 2-3 x size of a lymphocyte), with a high N/C ratio, round to oval nuclei, smooth nuclear borders and even chromatin pattern. The cohesive groups were usually in "saw-toothed" shaped clusters, also seen in our case. Ghost cells were present in clumps and singly and often had a refractile quality, a feature we saw…once we saw them! Recognizing this component is one of the pitfalls of making the diagnosis of PMX, and may be a feature only recognized after it is appreciated on a corresponding cell block. Giant cells were also a consistent features in Wang's series, and although present in our case, they were rare, easy to miss and none were photogenic. Calcifications may also be prominent but this feature was lacking in this case. Despite the variability of most of these features, this study concluded that both of the basic features of basaloid cells and ghost squamous cells must be present before a diagnosis of PMX is rendered.

The differential diagnosis of PMX includes various skin appendage tumors, salivary gland tumors such as pleomorphic and monomorphic adenoma and adenoid cystic carcinoma, and other malignant tumors such a squamous cell carcinoma, Merkel cell carcinoma, basal cell carcinoma and malignant small round cell tumor of childhood.

Malignancy is the most serious misdiagnosis due to the management implications. The basaloid and squamous cells often give rise to the over-diagnosis. In children, the basaloid cells can be mistaken for malignant small round cell tumors such as rhabdomyosarcoma, a sarcoma common in the head and neck. The absence of strap cells, anisonucleosis and the presence of cystic debris and ghost cells should preclude that diagnosis. A misdiagnosis of squamous cell carcinoma may occur due to an abundance of keratinized cells or even due to the basaloid cells being interpreted as a poorly differentiated component, and basal cell carcinoma is entertained because of the basaloid cells. The bland uniform nuclear features of both the basaloid and nucleated squamous cells and the presence of refractile ghost cells should prevent those interpretations. Neuroendocrine carcinomas such as metastatic small cell carcinoma and primary Merkel cell carcinoma are diagnostic considerations due to the small blue cells that can actually appear to have focal "molding". The tumor cells of these malignancies are larger, more pleomorphic and display coarse chromatin, generally no nucleoli, common mitotic activity and very commonly true tumor necrosis, not the cyst debris as seen in a PMX. Also, these malignancies do not have ghost cells! Adenoid cystic carcinoma, solid type, without the stromal balls, is also a malignancy to consider, but the absence of pain, the absence of cytological atypia and the presence of cyst debris and ghost cells dismisses that diagnosis.

Benign lesions in the differential diagnosis include salivary gland tumors and adnexal lesions. The absence of stroma essentially excludes the typical pleomorphic adenoma but cellular pleomorphic adenoma and monomorphic adenoma are considerations. Neither are usually cystic and neither contain ghost cells. In a man the presence of cyst debris introduces Warthin's tumor into the differential diagnosis, but basal cells are not a feature and the absence of oncocytic epithelium precludes that misdiagnosis.

A common misdiagnosis is that of a sebaceous cyst or epidermal inclusion cyst (EIC). Like PMX, EIC presents is the head and neck of young adults and children, but they are usually soft and rubbery rather than hard. Cytologically, they lack the basaloid cells, and the squamous cells of EIC are clumped and single delicate well defined anucleated squamous cells rather than fragmented and refractile ghost squamous cells of PMX. A ruptured EIC may present as a hard mass, and the addition of giant cells and inflammatory cyst debris adds to the diagnostic difficulty, but basaloid cells will still be absent. The presence of calcifications would also favor a PMX.

Trichilemmal cyst is another benign cutaneous nodule in the differential diagnosis. These lesions are typically encountered on the scalp and produce smoothly contoured, more maturing rather than consistently primitive appearing basaloid squamous cells with "saw-toothed" edges. Calcifications are also rare in these tumors. Given the commonality of the other features such as calcific debris, anucleated squames and giant cells, this subtle difference may be difficult to appreciate. Both are benign skin appendage neoplasms and would be treated similarly with conservative resection. In summary, PMX should be considered with the clinical presentation of a hard superficial cyst of the head and neck that produces a bland basaloid cell proliferation in a cystic background. The identification of scattered ghost squamous cells cinches the diagnosis. The presence of giant cells and calcific debris are icing on the cake.

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