Biphasic Squamoid Alveolar Renal Cell Carcinoma: 2 Cases in a Family Supporting a Continuous Spectrum With Papillary Type I Renal Cell Carcinoma

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To the Editor:
In a recent issue of the American Journal of Surgical Pathology published in May 2016, Hes et al1 reported a very interesting series of 21 cases of biphasic squamoid alveolar renal cell carcinoma (BSARCC), a recently recognized variant of renal carcinoma. Their results support the view that BSARCC could be “a distinctive subtype of papillary renal cell carcinoma” (RCC). Indeed, multiple chromosomal aberrations identified by aCGH always included gains of chromosome 7 and 17. Morphologic characteristic features were identical to the first 2 cases described by Petersson et al2 in 2012. BSARCC was composed of 2 distinct cell populations: a population of small cells with scant cytoplasm arranged in alveolar-like structures and a population of large eosinophilic squamoid cells with a large nuclei and prominent nucleoli. This last population forms nests in the alveolar-like structures and frequently exhibited emperipolesis. Both populations expressed CK7, EMA, AMACR, and vimentin. Interestingly, the most striking immunohistochemical feature was the expression of cyclin D1 being restricted to the squamoid cells.
All cases collected by Hes and colleagues were identified in patients with unifocal renal tumor and without personal or family history of papillary RCC. More recently, 2 cases of unifocal BSARCCs were identified in kidney allografts.3 Another report described the first multifocal case of BSARCC in a 68-year-old patient with 4 BSARCCs associated with a conventional clear cell RCC.4 Finally, Trpkov et al5 very recently reported 24 cases of BSARCCs at the 2017 USCAP annual meeting. Their findings confirmed that BSARCC can be multifocal (1 case) or associated with other subtypes of RCC (2 cases of papillary RCC, 3 cases of clear cell RCC). Interestingly, 1 case occurred in a patient with Birt-Hogg-Dube syndrome, a cancer susceptibility syndrome known to be associated with various types of renal cell tumors.6
To our knowledge, no case of familial BSARCC has been reported until now. Hence, we would like to report the first case of BSARCC occurring in a familial context of hereditary papillary RCC associated with MET mutation.
We recently received the right nephrectomy specimen of a 44-year-old male patient who underwent, 5 years ago, a left nephrectomy containing numerous type 1 papillary RCC (all pT1a). The right kidney contained about 30 well-delimited whitish tumors, ranging from 1 mm to 4 cm (all pT1a) (Fig. 1A). On microscopic examination, we were surprised to observe a typical pattern of BSARCC in many tumors (Figs. 1B, C) from 10% to 30% of areas. In some of them, BSARCC was clearly mixed with areas of classic type 1 papillary RCC. Immunohistochemistry was consistent with the diagnosis, including a selective cyclin D1 positivity in the central squamoid component (Fig. 1D).
The patient had a familial known MET mutation (c.A3523G, p.His1112Arg) inherited from his mother who underwent partial right nephrectomy followed by left nephrectomy 15 years ago at the age of 52. Multiple type I papillary RCCs were diagnosed (all pT1a except 1 tumor pT2b on the left). We reviewed the contralateral tumors of the patient and the bilateral tumors of his mother. For both of them, we could also identify areas of BSARCC in some of the tumors, leading to a morphologic spectrum ranging from pure papillary RCC to papillary RCC combined with BSARCC features (Figs. 1E–H).
We think that our observation provides another strong evidence that BSARCC is related to papillary RCC and seems to be more closely linked with type I papillary RCC. The clinical value of this subtype as well as the mechanisms involved in this peculiar aspect are still to be determined.
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