|Ahead of print
|Sarcomatoid variant of Xp11 translocation renal cell carcinoma: A rare case report in an adult female
Rakhi V Jagdale1, Supriya Jain2, Jaydeep N Pol3, Makarand V Khochikar4
1 Department of Pathology, Shri Siddhivinayak Ganapati Cancer Hospital, Miraj, Maharashtra, India
2 Consultant Pathologist, Apple Hospital and Research Institute Ltd., Apple Saraswati Multispeciality Hospital, Kolhapur, Maharashtra, India
3 Consultant Pathologist, Mahatma Gandhi Cancer Hospital, Miraj, Maharashtra, India
4 Chief of Uro Oncology, Shri Siddhivinayak Ganapati Cancer Hospital, Miraj, Maharashtra, India
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|Date of Submission||26-Nov-2021|
|Date of Decision||08-Feb-2022|
|Date of Acceptance||08-Feb-2022|
|Date of Web Publication||27-Jan-2023|
| Abstract|| |
Xp11 translocation renal cell carcinoma (XPTRCC) is a very rare kidney neoplasm, which has been predominantly reported in young patients. Sarcomatoid transformation in renal cell carcinomas is known. However, its occurrence in XPTRCC is unreported so far in the literature. We report a unique case of sarcomatoid transformation in a XPTRCC in a 23-year-old female, who presented with a huge right-sided renal mass and had metastatic deposits in lungs. Morphologically, clear cell morphology with papillary architecture along with foci of sarcomatoid transformation and rhabdoid differentiation were noted. Immunohistochemistry showed Pax-8 and TFE-3 expression in all components including the sarcomatous areas, whereas CK and EMA were expressed in conventional clear cell component. We present an extremely rare case of sarcomatous transformation in XPTRCC and discuss the case as determined by histopathology and immunocytochemistry. To our knowledge, this is the first case of sarcomatoid transformation XPTRCC being reported in the world literature.
Keywords: Sarcomatoid transformation, TFE-3, Xp11 translocation carcinoma
|How to cite this URL:|
Jagdale RV, Jain S, Pol JN, Khochikar MV. Sarcomatoid variant of Xp11 translocation renal cell carcinoma: A rare case report in an adult female. Indian J Pathol Microbiol [Epub ahead of print] [cited 2023 Dec 1]. Available from: https://www.ijpmonline.org/preprintarticle.asp?id=368570
| Introduction|| |
Xp11.2 translocation renal cell carcinoma (XPTRCC) was first reported by de Jong et al. in 1986. Originally thought to be an anomalous malignancy unique to children, it is being increasingly documented in adults. It was recognized as a distinct entity in 2004 WHO classification of kidney tumors. These tumors in adults unlike their pediatric counterparts present at an advanced stage with metastasis. Sarcomatoid transformation in an RCC is defined as a tumor of any histologic type containing foci of high-grade malignant spindle cells. Sarcomatous transformation is associated with a higher grade and poor prognosis. Hence, documentation of this transformation is essential however small the foci may be. It also helps the treating physicians in planning adjuvant therapy in metastatic tumors.
| Case Report|| |
A 23-year-old female presented with right-sided flank pain, fever, and hematuria since 3 months. Laboratory investigations were within normal limits except neutrophilia. CT scan of the abdomen revealed a large heterogeneous mass arising from the right kidney occupying almost half of the abdomen measuring 18 × 11 cm. CT chest showed multiple metastatic nodules in the left lobe of the lung along with enlarged right paratracheal, pretracheal, and hilar lymph nodes. An upfront cytoreductive right radical nephrectomy with hilar lymph node dissection was performed with the intent of adjuvant systemic therapy in view of her metastatic disease.
Gross examination revealed an enlarged kidney with a tumor measuring 15.5 × 10.3 × 8 cm. Cut section showed a nodular, variegated yellowish to grey-brown tumor involving the entire right kidney except the lower pole as shown in [Figure 1].
|Figure 1: Gross examination revealed an enlarged kidney with a nodular, variegated yellowish to grey-brown tumor involving almost the entire right kidney|
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Routine microscopy revealed a tumor with diverse morphology. The tumor was arranged in sheets, nests, and papillary architectural pattern. The cells had clear to abundant eosinophilic cytoplasm. The nucleus was vesicular with prominent nucleoli. Large foci of sarcomatoid and rhabdoid differentiation with necrosis and ossification were noted as shown in [Figure 2] and [Figure 3]. Good number of psammoma bodies were also seen.
|Figure 2: Microphotograph showing high-power view of large spindle-shaped cells displaying sarcomatous differentiation (HE x 40×)|
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|Figure 3: Microphotograph showing large rhabdoid cells. The cells have abundant cytoplasm and large vesicular nuclei and prominent nucleoli (HE x 40×)|
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On immunohistochemical evaluation, clear cell component expressed CK, EMA, PAX-8, and TFE-3 as shown in [Figure 4]. All other components including sarcomatoid areas expressed PAX-8 and TFE-3, while they were immunonegative for CK, EMA, CK7, CK20, and Melan A. Based on these features a diagnosis of Xp11.2 translocation RCC with sarcomatoid differentiation was made.
The patient had an uneventful recovery from the surgery. However, because of the rarity of this tumor, it was difficult to formulate adjuvant therapy in her case as no consensus are available for therapy in translocation Xp11.2 cases. Supportive care was offered to the patient; she survived for 14 months and died of extensive bilateral lung metastasis with hemothorax.
| Discussion|| |
Translocation carcinoma is a subtype of RCC that harbors a translocation involving a member of the microphthalmia transcription (MiT) factor gene family. These translocations most commonly involve the TFE3 gene on locus Xp11.2 and less commonly involve the TFEB gene on locus 6p21. The 2016 WHO classification has placed these tumors under the category of MiT family translocation carcinomas.
XPTRCC occurs predominantly, if not exclusively in children and young adults with a strong female preponderance., It is estimated that about one-third of pediatric RCCs are XPTRCCs. Adult XPTRCC is much more prevalent than originally perceived accounting for 1.6% to 5% of adult RCCs. The clinical presentation of XPTRCC is similar to other renal tumors. The most common symptom is hematuria, followed by abdominal pain and weight loss. Rare atypical presentations in adult patients include a heavily calcified renal mass, outflow obstruction with persistent pyelonephritis, renal cyst or nephrolithiasis.
The radiological findings of Xp11.2 RCC are not specific. However, in young patients, Xp11.2 RCC should be suspected if prominent lymph node metastases are present or the imaging findings are similar to those of papillary RCC.
Grossly these tumors have a morphology similar to other conventional RCCs. These are usually tan-yellow, necrotic, and hemorrhagic. Therefore, they may grossly mimic conventional clear cell RCC. A multilocular cystic gross appearance is uncommon.
On histology, XPTRCC requires morphologic distinction from renal neoplasms with clear cell morphology and papillary architecture: conventional clear cell RCC, papillary RCC, and clear cell papillary RCC (CCPRCC) are the close differentials.
Clear cell RCCs lack true papillae, psammomatous calcifications, and hyaline stromal nodules and are characteristically negative for both CK 7 and AMACR, although both may be focally positive, in higher-grade tumors. However, Cathepsin-K and TFE3, two markers of Xp11.2 TRCC are consistently negative.
Type II Papillary carcinomas with predominant solid pattern may have cells with plentiful voluminous cytoplasm along with good number of histiocytes having clear cell morphology and high-grade nuclei, which may cause diagnostic confusion with TRCCs. However, histiocytes are seen with hemosiderin deposition along the foci of necrosis and they reflect phagocytic activity of the renal carcinoma cells in these settings.
The immunohistochemical profile of papillary RCC characteristically shows strong membranous positivity for CK7. Cathepsin-K and TFE3 are both consistently negative. Cytogenetic studies show distinctive abnormalities unique to papillary RCC, including trisomy of chromosomes 7 and 17 along with loss of Y.
CCPRCC is a recently characterized, distinctive neoplasm, initially described in patients with end-stage renal disease, but is now known to arise in healthy kidneys as well. CCPRCC can show a wide range of architectural features, including true papillary structures, branching tubules, and solid nests or ribbons. The neoplastic cells contain clear cytoplasm, small-to-intermediate size round or irregular nuclei, and inconspicuous nucleoli. However, they lack foamy histiocytes, psammomatous calcifications or hemosiderin.
CCPRCCs show a distinct immunoprofile not seen in conventional RCCs. The neoplastic cells are positive for CK7 and vimentin, and negative for AMACR. Furthermore, no expression of cathepsin-K and TFE3 is observed in CCPRCC.,
XPTRCC show a heterogeneous pattern as described earlier. Significant heterogeneity can exist within the same tumor as was seen in our case as well. The diagnosis of XPTRCC should be considered in the following circumstances.
- Any RCC with clear cell and/or papillary pattern in an RCC in a patient under 35
- Any RCC with nests of cells with voluminous cytoplasm
- Any carcinoma with large number of psammoma bodies.
Immunohistochemistry can be useful in such cases. FISH or PCR may be required to confirm the diagnosis. The TFE3 fusion partner genes are recently characterized. Most common fusion partner gene is alveolar soft part sarcoma critical region 1 (ASPSCR1), der (17) t(X; 17) (p11.2;q25). This unbalanced translocation results in fusion of the TFE3 gene on Xp11.2, to alveolar soft part sarcoma locus (ASPL) on 17q25. Other known fusion genes are papillary renal cell carcinoma-TFE3 (PRCC-TFE3), t(X; 1) (p11.2;q21.2) and PTB-associated splicing factor-TFE3 (PSF-TFE3), t(X; 1) (p11.2;p34).
Sarcomatoid differentiation is an adverse prognostic factor having worse prognosis than grade 4 carcinomas. Sarcomatoid transformation in XPTRCC is documented in occasional case series only and to the best of our knowledge no case reports have been published.
| Conclusion|| |
XPTRCC is a rare malignancy where the genetic milieu leads to tumorigenesis and also determines the response to chemotherapy. It is necessary to diagnose this tumor entity accurately. Distinct histopathological and immunohistochemical features as described above may help pathologists in distinguishing these neoplasms from their mimics. Because of small number of TFE3 gene fusion-related tumors described in the literature, the exact biologic behavior and impact of current treatment modalities remain to be ascertained. Increased awareness among urologists, pathologists, and oncologists is indispensable in identifying more cases of this phenotype in the future and to help to formulate precise therapy.
An informed consent has been obtained from next of kin (The patient is deceased).
This case is part of series which has obtained ethical clearance from ethical committee.
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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[Figure 1], [Figure 2], [Figure 3], [Figure 4]
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