| Abstract|| |
Biphasic squamoid alveolar renal cell carcinoma (BSARCC) is a newly emerging distinct and rare morphologic variant of renal cell carcinoma (RCC). Morphological, immunohistochemical, and molecular data have shown that BSARCC is closely related to papillary RCC type 1. We report a case of Biphasic squamoid alveolar renal cell carcinoma with a rare presentation as cutaneous metastases. This variant tends to show an aggressive behavior. Hence, accurate histopathological diagnosis can help in effective treatment and for close follow-up of the patients.
Keywords: Biphasic squamoid alveolar renal cell carcinoma, cutaneous metastases, morphologic variant
|How to cite this article:|
Sherin S B, Gunabooshanam B, Sundaram S, D' Cruze L. Biphasic squamoid alveolar renal cell carcinoma: A rare entity with an even rarer presentation as cutaneous metastases – A case report. Indian J Pathol Microbiol 2023;66:174-6
|How to cite this URL:|
Sherin S B, Gunabooshanam B, Sundaram S, D' Cruze L. Biphasic squamoid alveolar renal cell carcinoma: A rare entity with an even rarer presentation as cutaneous metastases – A case report. Indian J Pathol Microbiol [serial online] 2023 [cited 2023 Mar 20];66:174-6. Available from: https://www.ijpmonline.org/text.asp?2023/66/1/174/367993
| Introduction|| |
Biphasic squamoid alveolar renal cell carcinoma (BSARCC) is a newly emerging morphologic variant of renal cell carcinoma (RCC). This distinct entity was first described by Petersson et al. in 2012. BSARCC is considered to be closely related to papillary RCC type 1 based on the morphological, immunohistochemical, and molecular similarities. These tumors are usually solitary and can even present as metastases. The most common sites of metastases in renal cell carcinoma are lung (45%) followed by bone (30%) and lymph node (22%). In general, cutaneous metastasis in renal cell carcinoma is very rare. We herein report this recently evolving variant of RCC termed as biphasic squamoid alveolar RCC with a rare presentation of multiple cutaneous metastases.
| Case History|| |
A 65-year-old man presented with complaints of multiple subcutaneous nodules on his chest wall for 2 months. The patient had an imaging report of CT-KUB (Computed tomography of kidneys, ureters, and bladder) which was done outside. CT-KUB revealed an exophytic ill-defined lesion in the left kidney. One of the subcutaneous nodules was excised and sent for histopathology examination in our institute.
Gross examination of the specimen showed a well-defined solid, grey-white lesion measuring 2 × 0.8 × 0.5 cm [Figure 1]a. Scrape cytology smear showed a high-grade malignancy with oncocytic morphology and focal emperipolesis [Figure 1]b. Microscopic examination of the routine sections showed an infiltrative lesion in the dermis with tumor cells arranged predominantly in alveolar pattern along with tubular pattern in few areas [Figure 1]c. On higher power, two population of cells were noted. The alveolar spaces were lined by small cuboidal cells. These cells showed scant cytoplasm with relatively uniform round nuclei. The center of the alveolar structures showed solid nests of large squamoid cells. These cells had abundant cytoplasm and nuclei with prominent nucleoli. The larger squamoid cells had foci of emperipolesis [Figure 2]a. The lesion was found to infiltrate into the deeper muscle bundles focally [Figure 2]b. Histopathology confirmed the diagnosis of metastatic deposit.
|Figure 1: (a) Excision biopsy specimen showing a solid, grey- white firm lesion in the subcutaneous tissue. (b) Scrape cytology smear showing clusters of oncocytic cells with focal emperipolesis (marked in arrows) (H&E, X200) (c) Paraffin embedded sections showing the tumor cells arranged in alveolar pattern with a biphasic population of cells. (H&E, X200)|
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|Figure 2: (a) Biphasic tumor cell population composed of small cuboidal cells rimming around the alveolar spaces and large squamoid cells forming solid nests in the centre. The large squamoid cells show emperipolesis. (H&E, X400) (b) The tumor is seen infiltrating into the muscle bundles. (H&E, X200)|
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Immunohistochemical workup was done for further categorization. PAX 8 was diffusely positive thus confirming the primary renal origin of the tumor [Figure 3]a. CK7 showed diffuse membranous positivity in both the tumor cell population [Figure 3]b. Cyclin D1 was positive only in the larger squamoid cells [Figure 3]c. p40 was negative thus ruling out the possibility of squamous cell carcinoma [Figure 3]d. By histology and IHC, the case was reported as metastatic deposit in the chest wall from Biphasic squamoid alveolar variant RCC.
|Figure 3: (a) The tumor cells showing diffuse nuclear positivity for PAX8 (IHC, X200) (b) The biphasic tumor cell population showing diffuse membranous positivity for CK7 (IHC, X200) (c) Cyclin D1 showing selective immunostaining restricted to the larger squamoid cells in the centre of the alveolar spaces. (IHC, X200) (d) The tumor cells were negative for p40 (IHC, X100)|
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Further evaluation with positron emission computed tomography (PET-CT) confirmed a mass lesion in the left kidney [Figure 4]a. There were fluorodeoxyglucose (FDG) avid lesions in the subcutaneous plane and muscles scattered throughout the body [Figure 4]b. Patient also had multiple FDG avid lesions in both the lungs, left adrenal, and bones thus culminating as a disseminated disease. Subsequently, the patient lost to follow-up.
|Figure 4: (a) PET-CT showing FDG avid mass lesion (14.3 × 10.8 × 9.5 cm) in the upper and interpolar region of left kidney. (b) PET-CT showing multiple FDG avid subcutaneous nodules in the chest wall|
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| Discussion|| |
The spectrum of renal cell carcinoma has expanded in recent times to include many newly recognized entities. BSARCC is a rare newly described variant of renal cell carcinoma and has a distinct morphology. The first two cases were reported by Petersson et al. in 2012 followed by a series of 21 cases described by Hes et al. in 2016. Previous studies have shown that the age of presentation ranges from 53 to79 years and these tumors are found to have a slightly male predominance. Chartier et al. has recently documented the occurrence of this tumor in a hereditary setting with two cases showing a familial MET mutation. Moreover, this tumor has also been reported in two cases of renal allografts.
Renal cell carcinoma frequently metastasizes to the lungs (45%) followed by bones (30%) and lymph nodes (22%). The incidence of cutaneous metastases is very rare (2.8–6.8%) in renal cell carcinoma. The study by Hes et al. confirmed metastatic spread in 5 out of the 21 cases of BSARCC reported in their series. This tumor tends to have aggressive behavior and the incidence of metastasis, recurrence and death have been documented in 15% of patients.
The size of the tumor varies from 1.5 to 16 cm. The lesions are usually solitary. Rare incidence of mulifocality has been reported. The tumors were found to be more common in the left kidney. Grossly, the tumors are solid, firm and have white-grey to tan-brown cut surfaces.
On microscopy, the tumor can have varying architectural features like alveolar, solid, glomeruloid, and compact tubular pattern. The alveolar pattern is most frequently encountered. The distinct histologic feature of this tumor is the presence of biphasic cell population. The first population of small cuboidal cells appears to rim the alveolar-like spaces. These cells are relatively uniform with scant cytoplasm and have round to oval low grade nuclei. The second population of cells forms solid nests within the alveolar-like structures and are composed of large squamoid cells. These cells have abundant cytoplasm and show high-grade nuclei with prominent nucleoli. The presence of emperipolesis in these large cells is another striking feature. Observations by Hes et al. concluded that the morphology of the metastatic lesions is similar to the primary tumor.
The differential diagnosis of biphasic squamoid alveolar RCC includes metanephric adenoma (MA). MA can have papillary and solid growth, but lacks the characteristic biphasic morphology. The tumor should not be mistaken for squamous cell carcinoma (SCC). Absence of keratin pearls and intercellular bridges rules out SCC.
Data on immunohistochemical analysis show that tumor cells of biphasic RCC are uniformly positive for PAX8, CK7, EMA, Vimentin and AMACR. CD10 shows variable immunostaining and the tumor cells are negative for Carbonic anhydrase IX. Cyclin D1 shows immunostaining restricted to the large squamoid cells. This selective distribution of CyclinD1 positivity can help to clinch the diagnosis.
Few previously reported cases of BSARCC also showed components of type 1 papillary RCC on histology. Molecular genetic analyses revealed gains of chromosomes 7 and 17 in BSARCC thus reiterating the link between BSARCC and papillary RCC. The molecular data so far has shown that BSARCC is an aggressive variant that is closely related to papillary RCC and hence treated similarly to papillary RCC. Further studies are warranted to know the use of MET inhibitors. These are still on experimental trials.
| Conclusion|| |
The knowledge of the unique histologic pattern of this tumor can help recognize this variant even on a metastatic lesion. Accurate diagnosis of this distinct entity on histology can ensure effective management and rigorous follow-up of these patients since this variant tends to show an aggressive behavior. To conclude, further studies are warranted to understand the full spectrum of clinical behavior of this extremely rare and novel variant of RCC.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
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Conflicts of interest
There are no conflicts of interest.
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Department of Pathology, Sri Ramachandra Institute of Higher Education and Research, Chennai, Tamil Nadu
Source of Support: None, Conflict of Interest: None
[Figure 1], [Figure 2], [Figure 3], [Figure 4]