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To delineate and characterize the cytomorphologic features of pilomatrixoma (PMX) helpful in correct diagnosis of the lesion on fine needle aspiration cytology (FNAC).
Archival records of clinical findings, FNAC and histopathological reports of PMX cases were analyzed. Aspirate findings in 14 cases of PMX were correlated with detailed clinical data and subsequent histopathology on excisional biopsy. Different morphological findings were graded semiquantitatively from 0 to 3+.
The series showed female preponderance, with head and neck being the commonest site. Majority patients had a single tumor with mean size of 1.6 cm. Out of 14 biopsy proven cases of PMX, cytology findings revealed PMX in 7 cases on the basis of ghost cells, groups of basaloid cells, squamous cells in combination with multinucleated giant cells and calcium deposits in a background of debris. The main reasons for erroneous diagnosis were predominance of one component over the others and non-representative aspirated material.
The cytological features of PMX are characteristic and allow a conclusive diagnosis provided the smears are examined keenly bearing in mind the diagnostic traps that can mislead a cytopathologist.
Pilomatrixoma (PMX) also known as calcifying epithelioma of Malherbe is a skin appendage tumor of hair matrix origin which usually occurs on the face or upper extremities. It presents as a solitary, slow growing dermal or subcutaneous nodule and is rarely diagnosed clinically.[1,2] Although histologic features of this lesion are well recognized, pathologists continue to encounter difficulties in diagnosis on aspiration cytology.
Very few reports are available on the cytological features of PMX, and most of these are single reports.[4,5] In many cases, PMX has been erroneously diagnosed cytologically as an epidermal inclusion cyst (EIC), giant cell tumor, squamous cell carcinoma or malignant adnexal tumor.[5–8]
This study highlights the cytomorphological features that point towards the correct diagnosis of PMX on Fine needle aspiration cytology (FNAC) smears.
Archival record of 13 years period was evaluated at Pathology Department of our institute. Out of a total of 83,700 histopathology cases, only 53 cases were of PMX. This data shows how rare this tumor is. FNAC was performed in 14 out of those 53 cases of PMX prior to the surgical resection. Study includes these 14 cases with their clinical, cytological and histological findings discussed in detail.
The aspirations were performed by the cytopathologists with 23 gauge needle attached to a 10 ml disposable plastic syringe held with a Cameco's syringe holder. FNAC smears from all the 14 cases were processed in the same manner. The slides were air-dried for May-Grünwald–Giemsa (MGG) and wet–fixed for hematoxylin–eosin (H and E) and Papanicolaou (Pap) staining. All the surgical biopsies were processed according to the standard histological methods, and stained with hematoxylin and eosin.
A detailed histopathological and cytological analysis was done in all the cases and the various components such as basaloid cells, shadow cells, foreign body giant cells, nucleated squamous cells, calcium deposits, bare nuclei, neutrophils, macrophages, and anucleated squames were graded on a scale of 0 to 3+. A grade of “0” was rendered when particular component was not present. Gradings of 1+, 2+ or 3+ were given when the component was rarely, occasionally, or commonly present in FNAC smears, respectively [Table 1].
Histopathological diagnosis was considered as the definitive diagnosis. The histopathological findings were correlated in all the cases with their cytological findings whether diagnosed correctly or not on cytology. This comparative methodology highlighted the features that are missed in cytological smears. A retrospective review and categorization of the components was done in all the cases by carefully reexamining the FNAC smears and histological sections. At the time of review, all the components were graded on a scale of 0 to 3+ in an objective manner as shown in Table 1.
The 14 cases included eight female and six male patients with age ranging from 4 to 61 years (mean=26.4 years). Size of the lesion varied from 0.5 to 5 cm (mean=1.6 cm). Nine (64%) lesions were located in the head and neck region. A correct clinical diagnosis of PMX was made in only one case. Relevant clinical data, including the site of lesions and clinical observations are summarized in Table 2.
Histopathologically, all the cases had distinctive populations of basaloid epithelial cells and shadow cells in varying proportions. Basaloid cells had round to oval hyperchromatic nuclei and scanty cytoplasm. Shadow cells had eosinophilic cytoplasm and a central-unstained (optically empty) zone, corresponding to the site previously occupied by nucleus. Areas revealing apparent evolution of basaloid cells into shadow cells were also noticed [Figure 1]. In addition to the characteristic epithelial component, the tumor stroma showed variable degree of granulomatous reaction with keratin debris, foreign body giant cells, calcium deposits, and inflammatory cells. Areas of ossification were not found in any case.
Detailed comparative tabulation of cytological and histopathological features of different components in 14 cases of PMX is shown in Table 1. A confident first hand diagnosis of PMX on FNAC smears was given in case nos. 1, 2 and 13, because a diversity of cell types including basaloid, squamous, shadow and foreign body giant cells were seen in smears, although the proportion varied from case to case. On review, grading results showed that all these three cases had basaloid, shadow and foreign body giant cells varying from 3+ to 2+. Basaloid cells could be easily recognized lying singly or in sheets. They were mostly round with scant cytoplasm and indistinct cell borders [Figure 2]. Ghost cells having abundant cytoplasm with distinct cell borders and central unstained area were configured mostly in clusters [Figures [Figures33 and and4].4]. In case nos. 3, 5, 11, 12 and 14 after gradation done in review process, the definitive cytodiagnosis of PMX was given.
Case no. 4 was earlier categorised as adnexal tumor on the basis of predominance of basaloid cells and multinucleated giant cells. Careful reexamination of smears showed an occasional shadow cell in the FNAC smears, and the specific diagnosis of PMX was given on review of the FNAC smears.
In case nos. 6-8, there was predominance of squamous cells in the absence of basaloid cells which led to a mistaken diagnosis of EIC. Even careful review of the smears did not reveal graded findings to render a diagnosis of PMX, so EIC was retained as a differential diagnosis.
Aspiration was performed twice in case no. 9 with a gritty sensation on needling. Even on review of the smears, only foreign body giant cells and histiocytes were found with the absence of basaloid cells and shadow cells. A diagnosis of EIC was made on review. Histological sections revealed mainly large areas of calcification in addition to the basaloid cells, shadow cells and foreign body giant cells. The presence of calcification could be the possible reason for poor yield on FNAC smears.
Aspiration in case no. 10 yielded only fluid. We could find only macrophages and inflammatory cells on reexamination of the FNAC smears. Diagnosis on review was not changed and was kept the same as the initial diagnosis, i.e. benign cystic lesion. Histological section revealed cystic areas lined by collections of macrophages.
PMX is a fusiform tumor covered by normal skin which is located in the dermis and subcutaneous tissue. Although the lesion can appear at any age, it is commonly seen in children and is more common in females. In this study, the mean age of presentation was 26.4 years with predominance in females.
Majority of the tumors arise in head and neck region, the other sites being commonly affected are the upper extremities, trunk and lower extremities. Majority of the tumors (92.8%) in our study were located in head and neck region and upper extremities. Duflo et al. noticed maximum tumor size of 3 cm diameter, we observed 1.6 cm as the mean tumor size.
In this study, majority of the tumors (92.5%) were single. A low percentage (3.5%) of multiple lesions has also been reported by Rotenberg et al. In this series, correct clinical diagnosis of PMX was made in only one case. Studies indicate that even when examined by an experienced clinician, appropriate preoperative diagnosis is very difficult.
We observed that as compared to the number of PMX cases on histology (52 cases), the lesion is rarer in cytological specimens. Studies in the literature also reveal a similar finding. This relative scarcity of FNAC material is one of the reasons that pure adnexal tumors are underreported or misdiagnosed very often by the cytopathologists.
Corresponding to histology, fine needle aspirates of PMX contain distinctive cellular and non-cellular components. Our study shows that a combination of shadow cells, primitive-appearing basaloid cells with a high nuclear/cytoplasmic ratio, nuclei exhibiting evenly dispersed chromatin and foreign body giant cells in FNAC smears are helpful in making a precise preoperative diagnosis of PMX. The presence of calcification and nucleated squamous cells further supports the diagnosis. However, the diagnostic triad of basaloid cells, ghost cells and foreign body giant cells need not necessarily be present in all the cases. When the aspirate happens to be from the periphery of the tumor or from an early lesion, it will show a marked predominance of basaloid cells at times to the extent of absence of other components. Aspirates from older lesions may even show only ghost cells.[15,16]
In this series, we reviewed the cases and graded the cytopathologic and histopathologic features. This methodology gave a graded and objective documentation of the key identifying features for the lesion. At the same time, because of semiquantitative analysis, this method had the limitation of interobserver grading variability. Very few authors have worked on this aspect till now.
Lesions that mimic PMX are skin appendageal tumors, such as trichilemmal cyst and EIC, cylindroma, malignant neoplasms (squamous and basal cell carcinoma) and granulomatous lesions.[18,19] Skin appendage tumors, such as cylindroma, eccrine spiradenoma and hidradenoma, contain mainly basaloid cells as seen in case no. 4. FNAC smears of these lesions show a predominance of basaloid cells in cohesive, smoothly contoured groups which contrast with the typically irregular, saw-toothed edges of the cohesive to loosely cohesive monolayer sheets of basaloid cells seen in PMX. Shadow cells, mature nucleated squamous cells and multinucleated giant cells are rare to absent. Finding of occasional shadow cells on reexamination was the only pointer to further categorize adnexal tumor in this case.
Our study reveals that most commonly the cytological smears were misinterpreted as benign lesions (EIC, benign cystic lesion and fibrohistiocytic lesion). This diagnostic problem arises when the yield contains numerous keratinized squamous cells with scarcity of basaloid and shadow cells as in cases no. 6-8. Like PMX, EICs are often superficial in location, but are rubbery rather than hard on palpation and show a monomorphic population of delicate, well-delineated anucleated squamous cells that are present singly or in clumps. Basaloid cells are not seen. Multinucleated giant cells and debris are not seen, provided that the needle has been placed at the core of the cyst. If the cyst wall has been broken, a possible foreign body granulomatous reaction may be observed. It is very rare for epidermal cysts to undergo calcification. Dominance of squames on aspirate is the main confusing factor that leads to erroneous diagnosis of EIC.
In the absence of shadow cells, the cytologic diagnosis of PMX may be difficult. In our FNAC material, we could not find the shadow cells in case nos. 9 and 10, instead there was predominance of foreign body giant cells along with histiocytes and anucleated squames. The presence of shadow cells with characteristic central pale nuclear zone has been repeatedly reported in the literature as the most important cytologic feature for the diagnosis of PMX. However, despite their abundance in histologic sections, their detection was reported to be difficult in the cytologic smears and they may not be present at all. This is probably due to difficulty in detaching these cells during aspiration.
A granulomatous inflammation may be suspected if inflammatory cells and foreign body giant cells are predominant in the smears. Multinucleated giant cells in dermal aspirates may be observed in several conditions ranging from keratinous cysts, ruptured benign cysts, panniculitis to squamous cell carcinoma. To categorize the lesion, type of cells accompanying multinucleated giant cells should be given importance. In PMX, these cells correspond to a foreign body giant cell reaction adjacent to shadow cells.
Cystic change was observed in case no. 10, so only macrophages were present even on repeat FNAC and careful retrospective analysis did not reveal any additional findings which could suggest the diagnosis of PMX. Histological section revealed a cyst surrounded by hemosiderin laden macrophages. Cystic change in PMX has been described in early stage of PMX evolutionary process.
Salivary gland lesions also enter in the differential diagnosis of PMX, especially if the lesion is located in the parotid or submandibular area. In our study, the lesion was located in the preauricular region in case no. 11. Monomorphic adenoma and adenoid cystic carcinoma of the salivary gland both show abundant basaloid cells with clumps of eosinophilic stromal material. In the cribriform areas of adenoid cystic carcinoma, ball-like masses of hyaline globules are surrounded by uniform hyperchromatic basaloid cells. The identification of shadow cells and the keratin clumps of PMX aid in the proper diagnosis.
Certain features of the cytologic appearance of PMX are likely to cause confusion with malignancy. These include a high cellular yield, the presence of small primitive-appearing cells with a high nuclear-cytoplasmic ratio, prominent nucleoli, nuclear molding, mitotic figures and a background rich in debris and inflammatory cells resembling tumor necrosis. Studies show that PMX has been very often misdiagnosed as carcinoma[18,19,23,24]; however, in the present series all the FNAC smears were categorized as benign lesions only. We had stained the smears by MGG as well as Papanicolaou stain, so we could avoid the diagnostic trap of false over-interpretation of the basaloid cells as malignant. Study by Sánchez Sánchez et al. has shown that the nuclei of basaloid cells appear unduly enlarged in the air-dried smears. Features that aid in the recognition of a benign lesion include a bland and evenly distributed chromatin pattern, regular nuclear contours or membranes in the small, primitive, uniform cell population and lack of nuclear atypia in the squamous cells.
In conclusion, FNAC smears from a firm tumor located in the head, neck or upper extremities presenting in a young adult should be examined carefully to exclude PMX. Spectrum of characteristic cellular components and diagnostic trap arising most commonly due to predominance of one component over the others should always be considered while examining FNAC smears to avoid incorrect diagnosis on cytology.
Source of Support: Nil
Conflict of Interest: None declared