Thyroid-like Follicular Renal Cell Carcinoma: An Emerging Entity

Objective: To study the clinicopathologic features of thyroid-like follicular renal cell carcinoma. Methods: Clinical data were collected in 5 cases of thyroid-like follicular renal cell carcinoma. HE staining and immunohistochemistry were carried out in surgically-removed specimen to analyze the clinical and pathological features with review of the literatures. Results: The patients aged 20-55 years, with one male and four females; the tumor occurred in the left kidney in three cases and right kidney in two cases. One case had a history of thyroid papillary carcinoma 3 years ago, and the patient had left flank pain, macroscopic haematuria for 2 weeks. The rest four cases had no consciousness of clinical symptoms and signs, without history of thyroid gland surgery; the physical examination found a mass in the kidney and normal thyroid glands. Three patients underwent radical nephrectomy, and the other two patients underwent tumor partial nephrectomy. The tumors were 2-4 cm in size. They showed a solitary nodular mass of well circumscribed with taupe and gray on cut surface. Microscopically, most of tumor cells arranged in thyroid follicular pattern in different sizes, with papillary configuration in a small portion, in four cases; the follicular structure was intermixed with the papillary each half in one case. A large amount of thyroid colloid was deposited within follicule-like structure or papillary axis, lined by simple columnar cells or cubic cells, with obvious atypia, ground-glass nuclei, nuclear groove and rare mitosis. Immunohistochemical staining showed tumor cells were positive for PAX8, and negative for thyroid transcription factor 1 (TTF1) and thyroglobulin (Tg). One of five patients presented with lymph node metastases (4/4) of renal hilum the same time in the diagnosis. Five cases were followed up for 5-84 months after operation, and no tumor progression was found. Conclusions: Thyroid-like follicular renal cell carcinoma is primary renal epithelial malignant tumor. The diagnosis mainly depends on its characteristics of histological appearance, namely similar to the histological morphology of well-differentiated thyroid follicular carcinoma and papillary carcinoma, and the metastasis from the thyroid papillary or follicular carcinoma must be excluded. On the premise of clinical history, immunohistochemical markers TTF1 and Tg have certain value in the differential diagnosis.

Thyroid-like follicular renal cell carcinoma (TLFRCC), also known as thyroid-like follicular carcinoma of the kidney or thyroid follicular carcinoma like renal tumor, is an exceedingly rare variant of renal cell carcinoma that has only recently been acknowledged. This neoplasm exhibits a distinct follicular morphology resembling that of the thyroid gland. Immunohistochemical analysis reveals positive expression of PAX8, Vimentin, and EMA, while thyroid-specific markers TG and TTF1 are consistently absent. Furthermore, there is a notable absence of any concurrent thyroid pathology on clinical evaluation. Previous reports have suggested that TLFRCC is an indolent, slow-growing malignancy with infrequent metastatic potential. In this report, we present a case of TLFRCC characterized by remarkable ossification and widespread metastasis, including multifocal pulmonary lesions, involvement of the abdominal wall, and infiltration into the psoas muscle. To our knowledge, this represents only the third documented instance of distant metastasis in thyroid follicular renal carcinoma. The current case demonstrates a therapeutic approach that combines radiotherapy with the utilization of toripalimab, a programmed cell death 1 (PD-1) receptor inhibitor, and pazopanib. This treatment regimen was tailored based on comprehensive genomic profiling, which identified mutations in the POLE (catalytic subunit of DNA polymerase epsilon) and ATM (ataxia-telangiectasia mutated) genes, both of which have been implicated in the pathogenesis of various malignant tumors. These findings represent a novel discovery, as such mutations have never been reported in association with TLFRCC. Thus far, this therapeutic approach has proven to be the most efficacious option for treating metastatic TLFRCC among previously reported, and it also marks the first mention of the potential benefits of radiotherapy in managing this particular subtype of renal cell carcinoma.

Thyroid-like follicular renal cell carcinoma is a rare subtype of renal cell carcinoma that has only been recently recognized, as most cases involve a solid tumor in one kidney. In this study, we report a rare case of bilateral renal cell carcinoma wherein the tumor in the left kidney was diagnosed as clear cell carcinoma, while the tumor in right kidney as thyroid-like follicular renal cell carcinoma. The difference between this case and the ones described in previous reports is that thyroid-like follicular renal cell carcinoma showed cystic changes on imaging. This suggests that when renal cystic lesions are encountered, we should consider the possibility of such rare tumors.

Renal cell carcinoma is responsible for approximately 80% of malignant tumors of the kidney. Clear cell, papillary, and chromophobe forms comprise the most frequent histological subtypes of renal cell carcinoma. Thyroid-like follicular renal cell carcinoma is an extremely rare subtype of renal cell carcinoma that resembles thyroid follicular neoplasms. Histologic findings should not be confused with chronic pyelonephritis with thyroidization or renal metastasis of thyroid cell carcinoma. There are few reports of thyroid-like follicular renal cell carcinoma. Here, we report a new case of thyroid -like follicular carcinoma of the kidney diagnosed in a partial nephrectomy specimen in a 62-year-old man.

Thyroidization of kidney reminiscent of thyroid follicles with accumulation of inspissated colloid-like material in renal tubules is a hallmark of chronic pyelonephritis. We identified 6 tumors in the kidney, distinct from currently known subtypes of renal cell carcinoma, with a striking histology that closely mimicked well-differentiated thyroid follicular neoplasms and raised the possibility of metastatic follicular thyroid carcinoma. Three occurred in males and 3 in females with an age range of 29 to 83 years and size range from 1.9 to 4 cm. All tumors were encapsulated and exclusively demonstrated follicular architecture comprising of microfollicles and macrofollicles containing inspissated colloid-like material. A minor component of small tightly packed follicles devoid of secretions was also noted. The follicles were lined by cells with moderate amphophilic to eosinophilic cytoplasm with round nuclei and occasional prominent nucleoli. The tumors were nonimmunoreactive with thyroglobulin and thyroid transcription factor 1 and for markers contemporarily used for renal differentiation. The tumors had a gene expression profile distinct from clear cell and chromophobe renal cell carcinoma. Comparative genetic hybridization failed to reveal cytogenetic alterations. Mean follow-up of 47.3 months (range: 7 to 84 mo) showed that 5 patients had no evidence of disease and 1 developed a metastasis to the renal hilar lymph nodes in which the follicular architecture with colloid was retained. Thyroid-like follicular renal cell carcinoma represents a unique histologic subtype of renal cell carcinoma of low malignant potential and its primary importance is to distinguish it from metastatic carcinoma from the thyroid.

Thyroid-like follicular renal cell carcinoma (TLFRCC), an emerging subtype of renal cell carcinoma, presents diagnostic challenges due to its resemblance to normal thyroid tissue. Here, we report a rare case of TLFRCC in a pediatric patient, a demographic rarely affected by this subtype. Histologically resembling a typical TLFRCC, our case exhibited unique features including post-neuroblastoma development, occurrence in a male teenager, and diffuse MelanA expression, which has not been previously reported in TLFRCC. Comprehensive genomic profiling revealed the EWSR1::PATZ1 fusion, confirming its genetic basis. Due to the advanced tumor stage, the patient received combined immunotherapy, and after a 9-month follow-up, remains tumor-free. Our case broadens the diagnostic spectrum of pediatric renal cell carcinomas, highlighting the importance of comprehensive molecular profiling in rare subtypes such as TLFRCC. Further research is needed to better understand TLFRCC's genetic landscape and optimize therapeutic strategies, especially in pediatric populations with evolving treatment protocols.

Thyroid-like follicular carcinoma of the kidney (TLFCK) is an extremely rare subtype of renal cell carcinoma (RCC) that histologically mimics primary follicular carcinoma of the thyroid gland. This new entity has not yet been integrated into the current WHO classification of renal tumors due to the limited data available. We report a further case of this rare histological entity, discuss the clinical, histological and immunohistochemical findings and provide an update on the review of the literature. A 73-year-old woman was found to have a left renal mass during her annual medical checkup. Her past medical history included high blood pressure and renal failure at hemodialysis stage. The patient underwent a nephrectomy with simple postoperative course. The tumor was described as being round, well circumscribed and dark brown in color. Histologically, the tumor showed follicular architecture with macro and micro follicles containing eosinophilic secretions or colloid-like material. Immunohistochemical studies demonstrated that the tumor cells exhibited no immunoreactivity for thyroid transcription factor-1 and thyroglobulin. The tumor cells showed intensive staining for cytokeratin 7 (CK7). The tumor cells were completely negative for CK20, WT1 and PAX8. Molecular biology was not carried out for lack of means. These findings are dissimilar to previously classified renal neoplasm. Thyroid-like follicular renal cell carcinoma represents a unique histologic subtype of renal cell carcinoma of low malignant potential and its primary importance is to distinguish it from metastatic carcinoma from the thyroid. A correct histopathologic diagnosis has important clinical and therapeutic implications. The current consensus from ISUP is not to recommend TLFCK as a new WHO histologic classification due to the small number of cases therefore, documentation of all cases available seems to be important to gain additional knowledge.

The International Society of Urological Pathology recently proposed classifying thyroid-like follicular renal cell carcinoma (TLF-RCC) as an emerging entity in renal epithelial tumors. Their entire proposal will be the framework for the next World Health Organization classification of renal tumors. Fewer than 15 cases of TLF-RCC have been reported in the literature up to date. We describe the multimodality imaging features of a patient with TLF-RCC. To our knowledge, this is the first case report in the literature commenting on the multimodality imaging appearance of this tumor.

Thyroid-like follicular renal cell carcinoma (TLFRCC) is a rare cancer with few reports of metastatic disease. Little is known regarding genomic characteristics and therapeutic targets. We present the clinical, pathologic, genomic, and transcriptomic analyses of a case of a 27-yr-old male with TLFRCC who presented initially with bone metastases of unknown primary. Genomic DNA from peripheral blood and metastatic tumor samples were sequenced. A transcriptome of 280 million sequence reads was generated from the same tumor sample. Tumor somatic expression profiles were analyzed to detect aberrant expression. Genomic and transcriptomic data sets were integrated to reveal dysregulation in pathways and identify potential therapeutic targets. Integrative genomic analysis with The Cancer Genome Atlas (TCGA) data set revealed the following outliers in gene expression profiles: CDK6 (81st percentile), MYC (99th percentile), AR (100th percentile), PDGFRA and PDGFRB (99th and 100th percentiles, respectively), and MAP2K2 (86th percentile). The patient received first-line sunitinib to target PDGFRA and PDGFRB and had stable disease for >6 mo, followed by nivolumab upon progression. To the authors’ knowledge, this is the first reported case of comprehensive somatic genomic analyses in a patient with metastatic TLFRCC. Somatic analyses provided molecular confirmation of the primary site of cancer and potential therapeutic strategies in a rare disease with little evidence of efficacy on systemic therapy.

Pathology 50 years on

EWSR1-PATZ1 fusion renal cell carcinoma: a recurrent gene fusion characterizing thyroid-like follicular renal cell carcinoma.

Emerging entities in renal cell neoplasia: thyroid-like follicular renal cell carcinoma and multifocal oncocytoma-like tumours associated with oncocytosis

Thyroid-like follicular renal cell carcinoma (TFRCC) is rare, with <50 cases reported in the litterature. Recently, Al-Obaidy et al. described recurrent EWSR1::PATZ1 fusions in TFRCC, supporting its classification as an independent entity1 . We report herein a diagnostically challenging case of TFRCC with sarcomatoid differentiation, aggressive clinical course and presence of an EWSR1::PATZ1 fusion.

Chapter 157 - Thyroid-like follicular renal cell carcinoma

The Genitourinary Pathology Society (GUPS) undertook a critical review of the recent advances in renal neoplasia, particularly focusing on the newly accumulated evidence post-2016 World Health Organization (WHO) classification. In the era of evolving histo-molecular classification of renal neoplasia, morphology is still key. However, entities (or groups of entities) are increasingly characterized by specific molecular features, often associated either with recognizable, specific morphologies or constellations of morphologies and corresponding immunohistochemical profiles. The correct diagnosis has clinical implications leading to better prognosis, potential clinical management with targeted therapies, may identify hereditary or syndromic associations, which may necessitate appropriate genetic testing. We hope that this undertaking will further facilitate the identification of these entities in practice. We also hope that this update will bring more clarity regarding the evolving classification of renal neoplasia and will further reduce the category of "unclassifiable renal carcinomas/tumors". We propose three categories of novel entities: (1) "Novel entity", validated by multiple independent studies; (2) "Emerging entity", good compelling data available from at least two or more independent studies, but additional validation is needed; and (3) "Provisional entity", limited data available from one or two studies, with more work required to validate them. For some entities initially described using different names, we propose new terminologies, to facilitate their recognition and to avoid further diagnostic dilemmas. Following these criteria, we propose as novel entities: eosinophilic solid and cystic renal cell carcinoma (ESC RCC), renal cell carcinoma with fibromyomatous stroma (RCC FMS) (formerly RCC with leiomyomatous or smooth muscle stroma), and anaplastic lymphoma kinase rearrangement-associated renal cell carcinoma (ALK-RCC). Emerging entities include: eosinophilic vacuolated tumor (EVT) and thyroid-like follicular renal cell carcinoma (TLFRCC). Finally, as provisional entities, we propose low-grade oncocytic tumor (LOT), atrophic kidney-like lesion (AKLL), and biphasic hyalinizing psammomatous renal cell carcinoma (BHP RCC).