A 65-year-old male presented with a 0.9 cm dome-shaped dark lesion on his upper chest. The clinical impression was basal cell carcinoma versus recurrent dysplastic nevus.

DS1 Fig1

Figure 1: Low-power examination revealed a dermal basaloid tumor that comprised nests with clear cell changes present.

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Figure 2: The clear cells are pleomorphic with a single large vacuole in their cytoplasm and a peripheral condensed hyperchromatic nucleus.

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Figure 3: PAS without diastase stain shows positive cytoplasmic red material (glycogen) in the clear cells.

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Figure 4: PAS with diastase stain is negative suggesting presence of glycogen but not mucin in the clear cells.

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Figure 5: The clear cells are strongly positive with EMA immunostaining.

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Figure 6: The peripheral basal cells are strongly positive with Bcl-2 protein immunostaining. The central clear cells are focally positive.

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Figure 7: Ki-67 stain demonstrates negative nuclear staining in the clear cells in the center compared to the positive peripheral basal cells.

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Figure 8: In contrast, a typical nodular basal cell carcinoma shows Ki-67-stained nuclei throughout the entire tumor nodule.

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Figure 9: The basaloid cells and clear cells share a similar p53 nuclear mutation pattern.

The lesion was completely excised with clear margins. Three years later, the patient remains free of any recurrence.

Diagnosis: Clear cell basal cell carcinoma

Comment:

Clear cell basal cell carcinoma was first described by Barr and Williamson in 1984 . A review of the literature to date reveals a total of 32 reported cases since that first description. Histochemical observations between cases have been inconsistent. PAS staining with and without diastase has been positive for glycogen in some cases but not in others . One report noted the presence of sialomucin deposition  constituting about 3% of the reported cases. Electron microscopic studies have also been variable, as some have observed the large intracellular vacuoles to be membrane bound , while others have not .

The differential diagnosis of clear cell basal cell carcinoma includes sebaceous carcinoma, clear cell squamous cell carcinoma, eccrine porocarcinoma, hidroadenocarcinoma, trichilemmal carcinoma, clear cell melanoma, and metastatic clear cell renal carcinoma. Sebaceous carcinoma cells with “foamy-bubbly” cytoplasm are positive for lipid on staining with Oil Red O or Sudan IV on frozen tissue and are positive with EMA and CAM 5.2 immunostaining. A small amount of cytoplasmic glycogen may be present. Clear cell squamous cell carcinoma is characterized by evidence of hydropic change of the neoplastic cells with accumulation of intracellular fluid and shows areas of squamous differentiation with foci of keratinization and keratin pearls. Unlike other cutaneous clear cell neoplasms, the accumulated fluid does not stain for glycogen, lipid, or mucin. The clear cells of eccrine porocarcinoma contain glycogen shown by diastase-resistant PAS positive cytoplasm. Moreover, they are positive with CEA and EMA immunostaining. The clear cells seen in eccrine hidroadenocarcinoma contain diastase-resistant PAS positive cytoplasmic glycogen. They are also positive with CEA and S-100 protein immunostaining. In contrast, clear cells in trichilemmal carcinoma have abundant glycogen but exhibit CEA and EMA negativity. The clear cell subtype of melanoma, also known as balloon cell melanoma, is usually S-100 and HMB-45 positive. Finally, the clear cells of metastatic renal cell carcinoma contain lipid (stained with Oil Red O) and glycogen but are negative for CEA and S-100 protein.

Because the clear cells of clear cell BCC stain positive for glycogen, the pathogenesis was initially suggested to be due to trichilemmal differentiation . Subsequent hypothesis have suggested that the large, clear membrane-bound vacuoles are phagolysosomes containing degradation products of intracellular organelles . However, the underlying mechanisms responsible for this histologic subtype of BCC are unknown.

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Sarma DP, Olson D, Olivella J, Harbert T, Wang B, Ortman S. Clear cell Basal cell carcinoma. Patholog Res Int. 2011 Apr 20;2011:386921. doi: 10.4061/2011/386921. PubMed PMID: 21559201; PubMed Central PMCID: PMC3090100.