Abstract
Xp11 translocation renal cell carcinoma (RCC) accounts for most pediatric cases of RCC but is uncommon in adults. It has an aggressive course in adults with poor response to chemoradiation. We describe a 64-year-old man with Xp11 translocation RCC who achieved complete remission following surgery and chemoimmunotherapy.
Keywords: Adult, remission, renal cell carcinoma, TFE3, Xp11.2 renal cell carcinoma
Neoplasms involving the kidney and renal pelvis comprise the eighth most common newly diagnosed cancer in the United States.1 Xp11 translocation renal cell carcinoma (XtRCC) is an uncommon neoplasm characterized by the fusion of transcription factor E3 (TFE3) gene. It accounts for most cases of pediatric renal cell carcinoma (RCC) but has a much lower incidence among adults. Adults with this tumor have a poor prognosis due to its aggressive clinical course. We report a case of stage 4 XtRCC in an older man who underwent radical nephrectomy and achieved complete remission with chemoimmunotherapy.
CASE REPORT
A 64-year-old white painter presented with fatigue and reduced appetite for 4 months. He also reported urinary frequency, dysuria, a 15-pound weight loss, and night sweats. He denied hematuria, abdominal pain, flank pain, chest pain, dyspnea, and cough. He was known to have hypertension, chronic back pain, and 52.5 pack-years of smoking. Medications included aspirin, atenolol, and atorvastatin. There was no known family history of malignancy. Examination disclosed no palpable lymphadenopathy, abdominal tenderness, organomegaly, or ascites.
Relevant laboratory studies are summarized in Table 1. Urinalysis was normal. Abdominal computed tomography revealed a 7.1 cm cystic mass at the upper pole of the right kidney with high attenuation and enhancing internal septation, consistent with cystic RCC. A right nephrectomy was performed. Morphology consisted of epithelial cells with clear cytoplasm and a papillary and cystic growth pattern (Figure 1). The nuclear grade was high (grade 3). By immunohistochemistry, alpha-methylacyl CoA racemase (AMACR) was positive. There was moderate to strong nuclear expression of transcription factor E3 (TFE3) (Figure 2). Carbonic anhydrase IX appeared positive around necrotic areas. The immunoprofile and morphology were consistent with XtRCC. Abdominal magnetic resonance imaging indicated osseous metastases in the thoracolumbar vertebral bodies, iliac wings, and ribs, which were confirmed by positron emission tomography (PET). The patient was started on axitinib and pembrolizumab. Follow-up PET demonstrated complete metabolic remission of previously noted metastases. He has remained in remission 12 months on maintenance axitinib.
Table 1.
Laboratory parameters at presentation
| Laboratory parameter | Observed value |
|---|---|
| Leukocyte count (×103 cells/μL) | 9.7 (H) |
| Hemoglobin (g/dL) | 12.7 (L) |
| Hematocrit (%) | 38 (L) |
| Platelet count (×103 cells/μL) | 420 (H) |
| Creatinine (mg/dL) | 0.97 |
| Calcium (mg/dL) | 10.3 (H) |
| Prostate-specific antigen (ng/mL) | 1.5 |
Figure 1.
(a) Low-power and (b) high-power microscopic images of histopathology depicting a predominantly papillary cellular architecture.
Figure 2.
Immunohistochemistry with strong nuclear positivity for TFE3.
DISCUSSION
Several researchers have studied the salient immunohistochemistry features of different RCC types (Table 2). XtRCC is characterized by translocations involving a breakpoint at the Xp11.2 locus, resulting in a fusion gene involving TFE3. This subtype accounts for 20% to 70% of pediatric RCC cases and 1.4% of adult RCC cases.2,3 Prior exposure to chemotherapy is the only known specific risk factor.4 The mean age of patients with XtRCC is 34.8 years with a 22:1 female:male predominance.5 Most have stage 4 disease at presentation.
Table 2.
Immunohistochemical markers utilized in renal cell carcinoma
| RCC subtype | Positive markers | Negative markers |
|---|---|---|
| Clear cell RCC | Vimentin, AE1/AE3, CD10, RCCM, PAX2, PAX8, CA IX | HMWCK, CK7, CK20, CD117, KSC, parvalbumin |
| Papillary, mucinous tubular, and spindle cell carcinoma | Vimentin, AE1/AE3, CK7, AMACR, RCCM, PAX2, PAX8 | CD117, KSC, parvalbumin |
| Chromophobe RCC/oncocytoma | E-cadherin, KSC, parvalbumin, CD117, AE1/AE3, CK7 | Vimentin, CK7 (or weak for oncocytoma), CA IX, AMACR |
| Xp11.2 translocation carcinoma | CD10, RCCM, TFE3, PAX2, PAX8, cathepsin-K | Usually negative or focally positive for AE1/AE3 |
| Clear cell papillary RCC | CK7, PAX2, PAX8 | AMACR, RCCM, CD10 |
| Urothelial carcinoma | HMWCK, CK7, p63, CK5/6, CK20, uroplakin III, GATA-3 | RCCM, CD10, PAX2, PAX8 |
| Myoid-rich or epithelioid angiomyolipoma | HMB-45, Melan-A, MSA, or SMA | AE1/AE3, CD10, RCCM, PAX2, PAX8 |
AE indicates anti-pan cytokeratin antibody; AMACR, a-methylacyl-coenzyme A racemase; CA IX, carbonic anhydrase IX; CD, cluster of differentiation; CK, cytokeratin; HMB, human melanoma black; HMWCK, high-molecular-weight cytokeratin; KSC, kidney-specific cadherin; MSA, muscle-specific actin; PAX, paired box protein; RCC, renal cell carcinoma; RCCM, renal cell carcinoma marker; SMA, smooth muscle actin.
XtRCC has a characteristic clinicopathology. A right-sided predilection has been reported.5,6 Tan/yellow-colored regions of macroscopic necrosis with hemorrhagic and cystic degeneration are noted.6 Neoplastic cells contain profuse clear or pale cytoplasm, with a predominantly nested, predominantly papillary, or mixed architecture.5 Psammoma bodies are frequently noted. Immunohistochemistry aids definitive diagnosis due to strong nuclear labeling for TFE3 protein. The TFE3 immunoreactivity assay carries the technical limitation of suboptimal fixation. This can be overcome by TFE3 break-apart fluorescence in situ hybridization.4
Surgery, particularly radical nephrectomy, remains the mainstay of management.7 There are limited data on nephron-sparing surgery in adults.8 Chemotherapy and radiation have been reported to be ineffective.9 Genetic studies are paving the way for targeted therapies with a scope for agents targeting mesenchymal epithelial transition tyrosine kinase, vascular endothelial growth factor receptor, and mammalian target of rapamycin.10,11 The prognosis is dismal in adults.9 One report noted that 83% of patients developed hematogenous dissemination and 33.3% died within a year of diagnosis.5 Advanced stage and inferior vena cava thrombosis predict a poor prognosis.9 Unfortunately, patients can develop distant metastases even decades after initial diagnosis, reiterating the need for good long-term follow-up.4
In conclusion, XtRCC is considered a pediatric cancer. The prognosis of adults is significantly worse than that of children. Our experience with this case was unique. First, as an older man, our patient is not typical of the demographics described for XtRCC. He had a remarkable response to chemoimmunotherapy with PET-proven negativity of previously active metastases. To the best of our knowledge, this is the first reported case of stage 4 XtRCC with complete remission after chemoimmunotherapy.
References
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