Clear Cell Basal Cell Carcinoma – A Rare Variant

Dear Editor,

A 65-year-old female presented with multiple hyperpigmented plaques over the right side of the face for the past 15 years, associated with intermittent pain and serosanguineous discharge from minor trauma. There was no history of fever or any preceding trauma. Examination revealed multiple well-defined hypertrophic hyperpigmented nodulo-plaques of size varying from 4 × 2 cm to 5 × 3 cm with rolled margins over the right mandibular region [Figure 1]. The surface of the plaque showed focal ulceration and bleeding with an overlying yellowish-white crusting. Partial loss of the lower part of the right earlobe was noted. Histopathological examination (HPE) was done with the differentials of basal cell carcinoma, discoid lupus erythematosus and deep fungal infection by punch biopsy, which showed tumor cells arising from the epidermis arranged in lobules and nests and infiltrating till the mid-dermis. The tumor was composed of basaloid cells showing peripheral palisading, with hyperchromatic nuclei, inconspicuous nucleoli, and scant cytoplasm along with brisk mitotic activity [Figure 2a]. Cells having a clear cytoplasm were composed of around 1/3^rd of the tumor cells [Figure 2b]. Periadnexal and perivascular lymphocytic inflammatory infiltrate was seen. Periodic acid Schiff (PAS) staining was positive [Figure 2c]. Immunohistochemistry staining showed CD10 [Figure 3a] and Bcl2 positivity in tumor cells along with BeREP4 [Figure 3b] and epithelial membrane antigen (EMA) negativity. The Ki 67 labeling index was 25% [Figure 3c]. The patient was diagnosed as a case of clear cell basal cell carcinoma (BCC). The patient declined the offer of surgical excision and was subsequently lost to follow up.

Figure 1.

Coalescing well-defined ulcerated hypertrophic hyperpigmented plaques present over the right mandibular region

Figure 2.

(a) Tumor cells composed of basaloid cells with peripheral palisading and hyperchromatic nuclei at low magnification (H and E, 10x) (b) with multiple cells with a clear cytoplasm seen (H and E, 40x) (c) and positive periodic-acid Schiff staining (40x)

Figure 3.

(a) Immunohistochemistry showing CD10 positivity (10x) (b) BrEP4 negativity (40x) (c), and a Ki67 labeling index around 25% (40x)

BCC is the most common type of cutaneous malignancy comprising almost 80% of cases of non-melanoma skin cancers.[1] Various histopathological patterns have been described in BCC, which include nodular, micronodular, superficial, infiltrative, morpheic, and mixed subtypes.[2] Clear cell BCC is a rare variant of BCC, first described by Barr and Williamson in 1984.[3] The presence of sialomucin deposition in a clear cell BCC was observed by Kim et al., and they hypothesized that tumor glandular differentiation might be responsible for the production of sialomucin.[4] However, now the reason behind the clear cell alteration appears to be degenerative change, and this may begin as an accumulation of phagolysosomes, which progresses to marked vacuolar change within the cytoplasm.[5] Electron microscopy studies have shown variable findings, as some have noted membrane-bound large intra-cellular vacuoles,[5,6] while others have noted them as being without a membrane.[7,8] Most clear cell BCCs are found to be mixed in the sense that they display both components – typical basaloid and clear cells along with the presence of transitional foci. Very rarely, cases may exhibit a predominant clear cell morphology.[6] Histochemical observations between cases have also been inconsistent. Some reports describe positive staining for glycogen with PAS (with or without diastase), as seen in our case, whereas others revealed sparse or no PAS positivity.[7]

Our case had BerEP4 negativity, which was unusual. The positive control used was colonic tissue. BerEP4 is a monoclonal antibody that detects EpCAM (epithelial cell adhesion molecule) and is a sensitive marker of BCC. The sensitivity and specificity of BerEP4 in detecting BCC have been found to be around 99.6% and 99.2%, respectively.[9] To the best of our knowledge, BerEP4 staining has been mentioned only in one case of clear cell BCC, in which it was reported as positive.[7]

Differential diagnoses in such cases may include clear cell squamous cell carcinoma (SCC), sebaceous carcinoma, and trichilemomma among others. Clear cell SCC is characterized by areas of squamous differentiation with keratin pearls and lacks BerEP4 positivity. Sebaceous carcinoma cells stain positive for lipid with Oil Red O or Sudan IV, and also show EMA positivity. Abundant uniformly PAS-positive glycogen has been observed in clear cells of trichilemmal carcinoma, but they exhibit CEA and EMA negativity.[7] Prognosis of this unusual variant of BCC is, however, not clear.[1]

Clear cell BCC is a rare and atypical variant of BCC. Histopathology along with immunohistochemistry, plays an important role in differentiating it from other tumors with clear cell change. Clinicians should be aware of this entity in order to differentiate it from its other histopathological mimickers.

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