Case 1 -
Martha Bishop Pitman
Harvard Medical School and Massachusetts General Hospital
Click on each slide thumbnail image for an enlarged view
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.
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
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
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
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
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.
- Daskalopoulou D, Galanopoulou A, Staturopoulou P, Papapetrou S, Pandazis I, Markidou S. Cytologically interesting cases of primary skin tumors and tumor-like conditions identified by fine-needle aspiration biopsy. Diagn Cytopathol 1998;19:17-28.
- Domanski HA, Domanski AM. Cytology of pilomatrixoma (calcifying epithelioma of Malherbe) in fine needle aspirates. Acta Cytol 1997;41:771-777.
- Gomez-Aracil V, Azua J, San Pedro C, Romero J. Fine needle aspiration cytologic findings in four cases of pilomatrixoma (calcifying epithelioma of Malherbe) in fine needle aspirates. Acta Cytol 1990;34:842-846.
- Kumar N, Verma K. Fine needle aspiration (FNA) cytology of pilomatrixoma. Cytopathology 1996;7:125-131.
- Lemos MM, Kindblom L, Meis-Kindblom JM, Ryd W, Willen H. Fine-needle aspiration features of pilomatrixoma. Cancer (Cancer Cytopathol) 2001;93:252-256.
- Ma KF, Tsui MS, Chan SK. Fine needle aspiration diagnosis of pilomatrixoma. A monomorphic population of basaloid cells with squamous differentiation not to be mistaken for carcinoma. Acta Cytol 1991;35:570-574.
- Ortiz J. Macias CG, Abad M, Flores T, Paz JI, Bullon A. Pilomatrixoma: a description of two cases diagnosed by fine-needle aspiration. Diagn Cytopathol 1995;12:155-157.
- Rege J. Shet T. Aspiration cytology in the diagnosis of primary tumors of skin adnexa. Acta Cytol 2001;45:715-722.
- Sanchez CS, Bascunana, AG, Quirante FAP, Romero MSM, Fernandez JC, Perez JS, Parra DM, Perez-Guillermo M. Mimics of Pilomatrixomas in fine-needle aspirates. Diagn Cytopathol 1996;14:75-83.
- Solanski P. Ramzy I, Durr N, Henkes D. Pilomatrixoma: cytologic features with differential diagnostic considerations. Arch Pathol Lab Med 1987;111:294-297.
- Thinakaran V, Singh SK, Simples P, Nadimpalli V. Fine needle aspiration diagnosis of pilomatrixoma. A case report. Acta Cytol 1998;42:769-771.
- Viero RM, Tani E, Skoog L. Fine needle aspiration (FNA) cytology of pilomatrixoma: report of 14 cases and review of the literature. Cytopathology 1999;10(4):263-9.
- Wang J, Cobb CJ, Martin SE, Venegas R, Wu N, Greaves TS. Pilomatrixoma: Clinicopathologic study of 51 cases with emphasis on cytologic features. Diagn. Cytopathol 2002;27:167-172.
- Woyke S, Olszewski W, Eichelkraut A. Pilomatrixoma: a pitfall in the aspiration cytology of skin tumors. Acta Cytol 1982;26:189-194.
- Wong MP, Yuen ST, Collins RJ. Fine-needle aspiration biopsy of pilomatrixoma: still a diagnostic trap for the unwary. Diagn Cytopathol 1995; 13(3):275-6.