Novel Case of Eosinophilic Solid and Cystic Renal Cell Carcinoma in a Pediatric Male
- 1. Department of Surgery-Urology, University of Mississippi Medical Center, USA
- 2. Department of Pathology, University of Mississippi Medical Center, USA
- 3. Department of Surgery-Pediatric Surgery, University of Mississippi Medical Center, USA
Introduction: Eosinophilic Solid and Cystic Renal Cell Carcinoma (ESC RCC) is a recently described morphologic subgroup of renal cell carcinoma (RCC). It was originally classified in patients with Tuberous Sclerosis Complex (TSC) but has since been seen to occur sporadically. The median age has been reported from 27 to 57 years with a roughly 13:1 female predominance. (1) The occurrence of this tumor subtype in a young adolescent male is highly unusual and rare. We present a case of ESC RCC arising as a single, incidentally discovered renal mass in a 17-year-old male.
Discussion: We present a novel case of ESC RCC in a pediatric male. Only three incidences of ESC RCC in the pediatric population have been documented prior to our case report, with only one occurring in a male. Compared to previous pediatric cases which featured multifocal lesions and one case of metastasis, our patient had a solitary, organ confined mass. Our patient’s tumor was identified as ESC RCC by reviewing the gross appearance of the mass and immunohistochemistry, most notably showing CK20 positivity which is uncommon in other RCC subtypes. At this juncture, ESC RCC is an emerging entity and is not formally recognized by the 2016 WHO classification of genitourinary tumors. However, it is our hope with this report to contribute to the further characterization of ESC RCC as a novel entity.
Eosinophilic Solid and Cystic Renal Cell Carcinoma, Urologic Oncology, Pediatric Urology, Urology, Nephrectomy
Azar CA, Adam Talley CMS, Manucha V, Sonani HH, Berch B, Bean CM (2021) Novel Case of Eosinophilic Solid and Cystic Renal Cell Carcinoma in a Pediatric Male. J Urol Res 8(1): 1127.
ESC RCC: Eosinophilic solid and cystic renal cell carcinoma; RCC: Renal cell carcinoma; TSC: Tuberous Sclerosis Complex; AML: Angiomyolipoma; IHC: Immunohistochemistry; SDH: Succinate dehydrogenase; FH: Fumarate hydratase; AST: Aspartate aminotransferase; ALT: Alanine aminotransferase
Eosinophilic Solid and Cystic Renal Cell Carcinoma (ESC RCC) is a recently described morphologic subgroup of renal cell carcinoma (RCC). It was originally classified in patients with Tuberous Sclerosis Complex (TSC) but has since been seen to occur sporadically. While these masses are young as a distinct entity, it is likely that they have historically been labeled as “unclassified RCC” with or without other descriptors such as “eosinophilic” or “oncocytic.”(2) The majority of cases occur in women and tend to be diagnosed at an earlier age (median age 48.5) compared to RCC as a whole. (3) Based on current data, ESC RCC appears to be indolent in nature with few cases of metastasis. (4) We present a case of ESC RCC arising as a single, incidentally discovered renal mass in a 17-year-old male.
17-year-old male with no previous medical history presented to emergency room reporting two days of right upper quadrant abdominal pain. He also had associated nausea, vomiting, and diarrhea over this time frame. CT scan revealed a four cm enhancing left renal mass concerning for malignant neoplasm. Transaminase levels were elevated with AST of 180 and ALT of 154. Aside from these findings, labs and imaging were unremarkable. Symptoms and transaminase levels resolved spontaneously. He underwent open left radical nephrectomy twelve days after initial presentation. No complications were encountered, and he recovered appropriately in the postoperative course. Pathologists at our institution classified the mass as an eosinophilic solid and cystic renal cell carcinoma. The tumor was limited to the kidney with negative resection margins. Five lymph nodes were analyzed and negative for carcinoma. The case was sent for outside consultation by the department of pathology at Brigham and Women’s Hospital in Boston, MA. After morphologic and immunohistochemistry testing, they agreed with the diagnosis of eosinophilic solid and cystic renal cell carcinoma. The patient was followed with periodic renal ultrasound and 2 view chest X-ray which were unremarkable up to 18 months after nephrectomy.
The earliest description of ESC RCC was in a case report detailing RCC in a patient with TSC by Schreiner et. al. (5) renal masses in the form of epithelioid angiomyolipoma (AML) are a well-characterized feature of TSC. However, the incidence of renal cell carcinoma within TSC is less common. Historical characterization of RCC remained poor due to inclusion of epithelioid AML in previous studies. (5) Through their case report, Schreiner et al. described a distinct RCC morphology seen in TSC featuring “sheet-like, glandular, trabecular, or cystic architecture and abundant eosinophilic cytoplasm.” (5) This unique iteration of RCC featuring “granular eosinophilicmacrocystic morphology”6 was investigated further by Guo et al. through a retrospective study of RCC in 18 patients with TSC.6 Of the 57 total masses catalogued, 11% were found to have similar characteristics to those described by Schreiner et. Al. (5-6)
The first formal reference to these morphologically unique masses as “Eosinophilic Solid & Cystic RCC” was by Trpkov et al. (2, 7) Through 2 studies they identified 19 cases of sporadically occurring RCC with morphology identical to that in the original TSC study. (5) They further stratified the immunohistochemistry (IHC) profile of ESCRCC highlighting predominantly CK20 positive/CK7 negative expressivity.
It has since been noted the ESC RCC occurs more commonly sporadically than in TSC association.4 Compared to sporadically occurring ESC RCC, the tumor appears to occur at an earlier age (mean 42 (6) vs. mean 57 (2)) in patients with TSC. (6, 2) In both sporadic & TSC associated ESC RCC there is a female predominance. Of 19 patients studied by Trpkov et. al, 100% were female. In the complete catalogue by Yunker et. al, which listed both sporadic and TSC-associated ESC RCC, 87% occurred in females. (4)
Within the literature only 3 pediatric cases of ESC RCC (2 females, 1 male) have been previously described as case reports. (4, 6) Both females were negative for TSC. The TSC status of the male (15 year-old) was unknown, however in a previous study this patient was noted to have a history of previous brain tumor which could occur in the context of TSC. (6) In Li Y et al’ s series of 33 unclassified eosinophilic renal cell carcinomas in young patients, 10 (30%) were ESC RCC, of which 2 were sporadic without a history of neoplasia or genetic syndrome (1 female and 1 male) and in 1 (female) the history was unknown. (1) In a subsequent study they demonstrated consistent TSC1 or TSC2 gene mutations using capture-based and amplicon–based next generation sequencing, in pediatric ESC RCC. All the pediatric ESC RCC were noted to have multifocal lesions (1) with two known incidences of metastasis to the liver. (1, 8)
At presentation, our patient was 17 years old. As previously described, he was admitted for work-up of gastrointestinal upset featuring nausea, hematemesis, bloody diarrhea, and abnormal liver function tests. It was on imaging that an incidental cystic appearing left renal mass was noted. While genetic testing was never performed, he has no known personal or familial history of TSC.
On gross examination, our patient’s mass was tan brown in appearance with intermixed solid and multi-cystic components and microscopic appearance in line with previously detailed characteristics of ESC RCC. (2, 6) (Figure 1-3).
Figure 1: On gross examination, revealed a solitary, well-delineated, tan-yellow mass measuring 4.6cm in greatest dimension. The cut surface showed a solid and cystic appearance.
Figure 2: (Figure 2 images A & B) On histology, the tumor lacked a well-formed capsule at the periphery and demonstrated uniform microscopic features with solid areas composed of sheets of eosinophilic cells, admixed with variably sized macro and microcysts.
Figure 3: The cysts were lined by cells exhibiting hobnail arrangement with voluminous eosinophilic cytoplasm. The cells in the solid areas typically showed diffuse and compact acinar or nested growth. Focal small aggregates of histocytes and lymphocytes were seen. The tumor cells showed abundant eosinophilic cytoplasm with prominent granular basophilic cytoplasmic stippling and round to oval, often irregular nuclei, with focally prominent nucleoli (equivalent to ISUP nucleolar grade 3).
IHC for our patient was positive for CK20, Succinate dehydrogenase (SDH), and Fumarate hydratase (FH), weakly positive for CK7, and negative for CD117 (Figure 4).
Figure 4: Immunohistochemistry showed positive patchy expression for CK20 (Image 5) and CK7. The tumor was negative for CD117, TFE3, and CA9. SDH (succinate dehydrogenase) and FH (fumarate hydratase) expression were intact.
As characterized by Trpkov et. al, the predominant IHC profile of ESC RCC includes “CK20 positive/ CK7-negative phenotype, patchy AMACR staining, but no CD117 reactivity.” (1, 2) The CK20 positivity in our patient strongly points to the designation of ESC RCC as CK20 is commonly negative in other subtypes of RCC. (2) In addition, positive staining for SDH and FH rules out 2 other recently described eosinophilic subclasses of RCC: Succinate dehydrogenase (SDH)-deficient RCC and Fumarate hydratase (FH)-deficient RCC. (1) While our patient’s tumor showed weak focal positive staining for CK7, in Trpkov et. al’s study 25% (4/16) of the masses were noted to be focally positive for CK7. Our patient’s tumor was staged at pT1b and confined to the left kidney. Of the catalogued cases in Yunker et. al’s paper, (4) 90% featured organ confined disease. This is compared to the roughly two thirds ratio of organ confinement for all cases of RCC. (3) With this in mind, organ confinement may be considered the rule among cases of ESC RCC. However, there are exceptions as four known cases of metastasis have been reported recently. (9) To date, our patient has displayed no signs of recurrence or metastasis from the original lesion.
Although it is not currently recognized as an independent entity by the WHO Classification of 2016 (updated 2018) (9- 10), new cases of ESC RCC continue to be identified. Including this case report, there are 62 identified cases of ESC RCC. (3) As pointed out by Yunker et. al studies of ESC RCC are predominantly within the scope of pathology as compared to urology. (4) While the course of ESC RCC appears to be indolent with an excellent prognosis, there is still much to be learned about any long-term clinical implications of ESC RCC particularly in pediatric cases.
There are many features that make our patient unique within the scope of ESC RCC. He will be only the eighth documented case of ESC RCC in a male, and the second pediatric male. When compared to three other pediatric cases, all three featured multifocal lesions and one incidence of metastasis, while our patient had a solitary lesion confined to the left kidney. It is our hope that this unique presentation of ESC RCC in a pediatric male will aid in further characterization of ESC RCC as a novel entity. It may also guide future diagnoses of ESC RCC especially in atypical patient populations and presentations.
6. Guo J, Tretiakova MS, Troxell ML, et al. Tuberous sclerosis-associated renal cell carcinoma: a clinicopathologic study of 57 separate carcinomas in 18 patients. Am J Surg Pathol. 2014; 38: 1457-1467.
7. Trpkov K, Abou-Ouf H, Hes O, et al. Eosinophilic Solid and Cystic Renal Cell Carcinoma (ESC RCC): Further Morphologic and Molecular Characterization of ESC RCC as a Distinct Entity. Am J Surg Pathol. 2017; 41: 1299-1308.
8. Palsgrove DN, Li Y, Pratilas CA, Lin MT, Pallavajjalla A, et al. Eosinophilic Solid and Cystic (ESC) Renal Cell Carcinomas Harbor TSC Mutations: Molecular Analysis Supports an Expanding Clinicopathologic Spectrum. Am J Surg Pathol. 2018; 42: 1166-1181.