INTRODUCTION
Rhabdoid differentiation in renal cell carcinoma (RCC) refers to the development of neoplastic cells that morphologically resemble rhabdomyoblasts, but differ in ultrastructural features and immunophenotype. A recent consensus statement of the International Society of Urological Pathology (ISUP) recommended reporting the presence of rhabdoid differentiation in RCCs and considering tumors with rhabdoid differentiation to be ISUP Grade 4.[1] At present, there are 280 reported cases of adult RCC with rhabdoid morphology in the English literature. We present a case of incidentally detected clear cell RCC with rhabdoid differentiation (RCC-R) at the stage of T1b, managed by partial nephrectomy.
CASE REPORT
A 52-year-old man presented with cough for 6 months associated with weight loss. He was a known hypertensive for 15 years. Physical examination revealed rashes in bilateral lower limbs. While evaluating for weight loss and cough, an abdominal ultrasonographic study showed a mass in the lower pole of the left kidney. Contrast-enhanced computed tomography (CT) scan confirmed the presence of an enhancing mass in the same location measuring 5.4 cm 5.3 cm 6.3 cm, without any perinephric extension [Figure 1a]. The renal vein and inferior venacava were normal. No locoregional lymphadenopathy was noted. CT scan of thorax revealed bronchitis.
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Figure 1: (a) Abdominal computed tomography scan image shows a contrast-enhancing lesion in the lower pole of the left kidney. (b) Gross photograph reveals a well-circumscribed tumor separated from the renal parenchyma by a fibrous pseudocapsule (arrow). The tumor is yellowish and reveals areas of hemorrhage and necrosis
At the time of his presentation, he had severe cough and wheezing. He was taken up for surgery 10 days later after a significant improvement in pulmonary functions. All his biochemical, hematological, and serological tests were in the range of normal. His nephrometry score for partial nephrectomy was seven. A lower pole partial nephrectomy of the left kidney was performed with 11th rib bed incision, and hilar vascular clamping time was 10 min.
Gross examination showed a well-circumscribed tumor measuring 5.5 cm in diameter [Figure 1b]. The tumor was yellowish with areas of hemorrhage and necrosis. Renal parenchymal and perinephric fat resection margins were uninvolved by tumor. Histopathological examination confirmed a well-circumscribed collision tumor composed of clear cells (20%) and rhabdoid cells (80%), with a transition zone between the two. The rhabdoid cells showed a discohesive sheet-like growth pattern, with focal alveolar pattern [Figure 2]. Microscopic necrosis was present involving <10% of the tumor. Sarcomatoid differentiation was not identified. The ISUP grade of nonrhabdoid component of the clear cell RCC was two. The tumor was diagnosed as clear cell RCC-R.
Figure 2: (a) Photomicrograph reveals transition zone (arrow) in between the area with cells showing rhabdoid differentiation (upper third) and clear cells (lower third) (H and E, ×100). (b) Higher magnification of areas with rhabdoid differentiation characterized by cells with abundant eosinophilic cytoplasm and large eccentric nuclei with prominent nucleoli that resemble rhabdomyoblasts (H and E, ×200)
His postoperative follow-up was uneventful. Following the histopathology report, the patient is under close surveillance with regular follow-up being advised.
DISCUSSION
RCC-R is a rare but aggressive pattern of differentiation that is present in 3-7% of RCC cases. Although it can occur in association with any histologic subtype, it is most frequently associated with clear cell RCC.[1] It is characterized by cells with abundant eosinophilic cytoplasm and large eccentric nuclei with prominent nucleoli that resemble rhabdomyoblasts.
Recognition of aggressive nature of RCC-R is reflected in the recent consensus statement of the ISUP on grading of RCC and other prognostic parameters. At the 2013 ISUP meeting, it was agreed upon by majority (73%) of the survey respondents that the presence or absence of rhabdoid differentiation should be specified in the surgical pathology report. It was also agreed that in renal tumors with rhabdoid differentiation, if there is evidence of histologic type, the diagnosis should be this subtype with rhabdoid differentiation.[1] Our case showed rhabdoid differentiation in 80% of the total tumor area, with clear cell morphology in 20% of the area. Hence, a diagnosis of clear cell RCC-R was made.
There are currently 280 reported cases of RCC-R in literature.[2,3,4] This is first such case reported from Indian subcontinent. An early comprehensive series of 480 RCC patients, including 23 with rhabdoid differentiation, by Gökden et al. revealed that RCC-R was related to higher clinical stage and Fuhrman grade. Subsequent reports by various authors have confirmed the finding with majority of RCC-R (80%) reported till date presenting at a stage later than T3.[3] The tumor in the current study was incidentally detected at a very early stage (T1b) with no extrarenal extensions or metastasis.
The ISUP grade of the nonrhabdoid, nonsarcomatoid component would be Grade 3 and Grade 4 in majority of RCC-R reported till date.[3] Interestingly, ISUP grade of nonrhabdoid component was two in the current case.
It has been hypothesized that rhabdoid cells represent a de-differentiation of the parent RCC cells akin to sarcomatoid differentiation. Evidence for this assertion includes the frequent observation of "transition areas" where rhabdoid cells are seen to arise in close association with cells of the parent RCC, similar epithelial immunohistochemical profile between RCC and associated rhabdoid cells and a finding of identical mutation profiles in both RCC and rhabdoid cells.[5] The ultrastructural basis of rhabdoid phenotype has been shown to be aggregation of cytoskeletal filaments, rather than true skeletal muscle differentiation.[2] Transition areas were observed in the current case also.
Recent reports by Przybycin et al. and Zhang et al. differ on whether rhabdoid differentiation in RCC confers an increased risk of death, independent of other prognostic factors in Grade 4 RCC.[3,4] However, both series support the most recent ISUP grading system, classifying any tumor with rhabdoid differentiation as Grade 4. Accordingly, tumor in the current study was assigned ISUP Grade of 4.
Currently, there is a lack of established guidelines regarding the management of patients with RCC-R. In most cases reported thus far, surgery has been the preferred modality of management with radical nephrectomy being preferred in 90% of such tumors. In view of the nephrometry score for partial nephrectomy being seven in the current patient, partial nephrectomy was performed.
In summary, rhabdoid differentiation in RCC is an indicator of aggressive behavior and represents an important addition to surgical pathology report and should be incorporated into grade assessment as one of the definitional types of ISUP Grade 4. In view of the differences in biologic behavior of RCC-R, specific guidelines for its management need to be established along with exploring of newer modalities.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
Acknowledgment
We thank our institute NU Hospitals, Bengaluru, for encouraging us to publish this rare case.
REFERENCES
1. Delahunt B, Cheville JC, Martignoni G, Humphrey PA, Magi-Galluzzi C, McKenney J, et al The International Society of Urological Pathology (ISUP) grading system for renal cell carcinoma and other prognostic parameters Am J Surg Pathol. 2013;37:1490–504
2. Gökden N, Nappi O, Swanson PE, Pfeifer JD, Vollmer RT, Wick MR, et al Renal cell carcinoma with rhabdoid features Am J Surg Pathol. 2000;24:1329–38
3. Przybycin CG, McKenney JK, Reynolds JP, Campbell S, Zhou M, Karafa MT, et al Rhabdoid differentiation is associated with aggressive behavior in renal cell carcinoma: A clinicopathologic analysis of 76 cases with clinical follow-up Am J Surg Pathol. 2014;38:1260–5
4. Zhang BY, Cheville JC, Thompson RH, Lohse CM, Boorjian SA, Leibovich BC, et al Impact of rhabdoid differentiation on prognosis for patients with grade 4 renal cell carcinoma Eur Urol. 2015;68:5–7
5. Perrino CM, Hucthagowder V, Evenson M, Kulkarni S, Humphrey PA. Genetic alterations in renal cell carcinoma with rhabdoid differentiation Hum Pathol. 2015;46:9–16
