Solid Papillary renal cell carcinoma (with spindle cell and tubular components, mimicking mucin poor mucinous tubular and spindle cell carcinoma)
- A sharply demarcated/well-circumscribed large tumor mass with a solid pale gray-white nodular cut surface in upper pole of kidney. Occasional areas of hemorrhage are seen. Cystic changes are not seen.
- A well-circumscribed cellular tumor with fibrous pseudo capsule. Tumour component is well-demarcated from adjacent normal renal parenchyma with a layer of inflammatory cells, but without stromal desmoplasia.
- Cellular solid appearing tumor (approximately 75% of total tumor area) with spindle cell pattern. This spindle element in a broad cellular fascicles and sheet show scanty cytoplasm and hyperchromatic, moderately pleomorphic nuclei. Some foci of hyalinised nodule is also seen.
- Tightly compressed tubular structures, short abortive papillae and glomeruloid like structures (approximately 20% of total tumor area) also giving a solid appearance.
- Areas of irregular, dilated and elongated tubules with surrounding fibrovascular septa, giving solid-alveolar pattern
- Few structures of papillae with hyalinised fibrovascular core is seen (approximately 5% of total tumor area)
- Tumor cells have round to elongated nuclei with vesicular nuclei, fine chromatin, small nucleoli, occasional nuclear grooves, moderate pleomorphism and pale to clear cytoplasm (International Society of Urological Pathology [ISUP] nucleolar grade 2). Rare mitoses are seen.
- Dense eosinophilic hyalinised tissue mimicking osteoid are seen. Some blood vessels show hyaline arteriosclerosis
- Foamy macrophages and necrosis are not present.
- Strong and diffuse positive for CK7. CK7 highlights the tubular architecture.
- Vimentin is patchy and weak positive.
- BCL-2 is very focal and weak positive.
- WT-1, CD99 and NSE are negative. CD99 stain image shows cells with intranuclear grooves (marked areas)
- Ki-67 index is less than 1%.
Practical Points of Pathoclinics:
- Papillary renal cell carcinoma (PRCC) should contain at least 50% true papillae. Morphologic variation in papillary RCC include trabecular, tubular, sclerotic, high-grade papillary RCC, all are with at least 50% true papillae. Papillary RCC containing minor foci of solid areas is common finding in routine practice. However, predominant solid component, devoid of distinct papillary structures are highly uncommon findings and few cases of solid papillary renal cell carcinoma (Solid PRCC) are reported in the literature, with incidence of less than 1% of all renal tumors.
- Solid PRCC more commonly affecting male, in age range from second to eight decade of life.
- Grossly, Solid PRCC is usually well-circumscribed, solid, light yellowish-white mass with some nodular appearance like present case. Haemorrhage, cystic changes and necrosis are uncommon. Tumor size range from 1.4 to 5.5 cm. Bilateral solid PRCC is very uncommon.
- Histomorphology of solid PRCC is different from type 1 and type 2 PRCC. According to the published literature, solid PRCC composed of predominantly solid sheets of cells resembling to that of type 1 PRCC (monomorphic epithelial cells with scant cytoplasm and small nuclei, however some case may show abundant clear cytoplasm), areas of small compressed tubules, compressed short abortive papillae and glomeruloid structures, and areas resembling spindle cell component. These spindle cell component should be of low-grade and has same immunostaining pattern that of epithelial cells. Presence of true papillae with fibro-vascular core is very uncommon. Some case may show solid alveolar pattern like present case. Definite consensus on percentage of true papillae for designation of solid PRCC has not been define yet, but overall literature suggesting less than 5% to 20% of total tumor area. Almost all solid PRCC is a well-circumscribed or capsulated tumor and show low ISUP grade, up to 2. Foamy macrophages and psammoma bodies may be seen, similar to conventional PRCC.
- Spindle cell area of solid PRCC is usually low grade with ovoid to elongated nuclei, moderate pleomorphism, finely dispersed chromatin, and distinct nucleoli. These cells resembled the cells of mucinous tubular and spindle cell RCC. Necrosis and mitoses are rarely seen. High grade sarcomatoid changes are not seen; if present, than consider alternative diagnosis as this features are not compatible with morphology, prognosis and outcome of solid PRCC, described in the literature.
- On immunohistochemistry, solid PRCC usually stains positive for CK7, cytokeratin 8/18, EMA, AMACR (racemase), focal vimentin, focal CD10, cytokeratin AE1/AE3, CAM5.2, high–molecular weight cytokeratin, and RCC, both in the tubular and spindle cell elements, which is common with routine papillary RCC. Solid PRCC is negative for WT-1, cytokeratin 20, CD57, synaptophysin, desmin, smooth muscle actin, myogenin, and leukocyte common antigen (CD45). Proliferative activity is usually between 1% and 2% by KI-67 in all reported tumors, including preset case.
- Regarding Bcl-2 expression, it is usually negative in clear cell RCC, not in all cases, while weak patchy positivity seen in some PRCC. Collecting duct carcinoma, chromophobe RCC and RCC with sarcomatoid transformation are also positive for Bcl-2. Some report suggest BCl-2 expression as a better prognostic marker, but still detailed prognostic significance of Bcl-2 is lacking.
- Genetic study of solid PRCC shows trisomies of chromosomes 7 or 17, and loss of Y, similar to conventional PRCC and some cases of mucinous tubular and spindle cell carcinoma (MTSC).
- As per the literature review, most solid PRCC are in pT1 and most has ISUP grade of 1, some with grade 2, and has a favorable clinical course. Occasional case may show capsular and perirenal adipose tissue invasion, recurrent tumour and metastasis. Low grade spindle cell component does not impact the prognosis in contrast to high grade spindle cell component, which carries poor prognosis.
- The term papillary is not idealistic, in view of very small or sometimes absent papillary structures, but due to similarities of immunomarkers and genetics profile, prognosis and long-term outcome, descriptive designation of solid PRCC is sufficient for these extremely rare or truly underreported tumor.
- In present case, morphology and immunomarkers are closely resemble to that of mucinous tubular and spindle cell carcinoma (MTSC) especially mucin poor type. MTSC is characterized by elongated and compressed tubules and cordlike structures, of uniform low grade cuboidal cells with eosinophilic, focally vacuolated cytoplasm and distinct spindling of cells, in an extracellular blue-gray mucinous/myxoid matrix. Cases of solid PRCC with very occasional or absent papillae are difficult to distinguish from mucin poor MTSC. Both PRCC and MTSC may have low-grade spindle cell foci. Adequate sampling of tumor is essential to detect the presence of mucin and myxoid component of MTSC. Both solid PRCC and MTSC are well-circumscribed, solid whitish tumor and can have tubular structures, variable number of papillary architecture, spindle cell appearance, psammoma bodies, foamy macrophages, and positive staining for vimentin, CK7, CK19, HMWCK, EMA, AMACR, CD10, E-cadherin and RCC. KI-67 index is low in both solid PRCC and MTSC. Presence of fibrous septa, nuclear groves, psammoma bodies more favour, but not specific for solid papillary RCC. Some studies observe the neuroendocrine differentiation in MTSC, but not in solid PRCC. Genetic analysis of some MTSC typically demonstrate losses of multiple different chromosomes and lacks the trisomies of chromosomes 7 and 17; however, some studies show gains of chromosomes 7 and 17 and loss of Y, similar to papillary RCC. These findings raise the possibility of MTSC being a spectrum or subtype of solid PRCC. Both tumors are low-grade malignant renal tumor.
- Other common differentials of solid PRCC are metanephric adenoma; epithelioid nephroblastoma/Wilms’ tumor and oncocytic variant of PRCC. Prominent spindle cell component may misquarrel with synovial sarcoma.
- Metanephric adenoma is a well-demarcated solid tan color tumor of mostly young female. Metanephric adenoma composed of tightly packed tubules, acini, abortive papillae and glomeruloid structures in an edematous or hyalinized stroma, however, metanephric adenoma is positive for WT-1, CD57 and kidney specific catherin, while negative for CK7 and AMACR. Immunohistochemical detection of BRAF V600E mutations can be used for diagnosis of metanephric adenoma. BRAF V600E mutation is not seen in other renal tumors.
- Nephroblastoma is very rare in adult patients but similar in morphology to that of pediatric counterpart. Nephroblastomas are diffusely positive for WT-1, and very rare focal positive for CK7. Nephroblastomas don’t have polysomy/trisomy of chromosomes 7, 17, and Y present.
- An oncocytic variant of PRCC can show solid pattern along with similar immunoprofile and genotype of PRCC. Despite the solid architecture, oncocytic PRCC can be differentiated from solid PRCC based on oncocytic appearance of cell, while solid PRCC contain smaller size of epithelial cells with scanty cytoplasm.
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