Despite significant progress regarding clinical detection/imaging evaluation modalities and genetic/molecular characterization of pathogenesis, advanced renal cell carcinoma (RCC) remains an incurable disease and overall RCC mortality has been steadily rising for decades. Concomitantly, clinical definitions have been greatly nuanced and refined. RCCs are viewed as a heterogeneous series of cancers, with the same anatomical origin, but fundamentally different metabolisms and clinical behaviors.
TYPE | MYCROSCOPY | IHC STAINING | GENETICS | |||||
---|---|---|---|---|---|---|---|---|
Clear cell (cc) RCC | Clear cell PopulationHypercellularity | : nests/sheets of cells, manifesting cytoplasmatic clearing and individualized membranes. Granular eosinophilic cytoplasm, seen in high-grade areas or near hemorrhage/necrosis. Rarely, intra/extracellular hyaline globules, basophilic cytoplasmic inclusions, abundant multinucleated giant cells. Architecture: solid, alveolar/nested, acinar/tubular, microcystic/macrocystic, rarely pseudopapillary. Stroma: ussually nonspecific, without desmoplasia or inflamatory modifications; may be fibromyxoid, with calcification/ossification. Hypervascular tumor: ramified network of small calibre, thin-walled vessels. |
CAIX CK7High grade features: rhabdoid/sarcomatoid differentiation. |
CD117 Cathepsin-K HMB-45POSITIVE | : PAX8 (nuclear, ~100%); CAIX (diffuse membranous/box-like, 75–100%); proximal tubular antigens (also seen in normal cells): CD10 (membranous, 82–94%) and RCCm (cytoplasmic and membranous, 72–84%); epithelial markers (AE1/AE3, CAM 5.2, EMA); Vimentin (cytoplasmic and membranous). NEGATIVE: CK7 (focally positive or patchy in high grade areas or cystic components); CK20; AMACR; 34βE12; CD117; HMB-45; TFE3/TFEB; Cathepsin-K; GATA3; MelanA; Inhibin. |
SPORADIC: | ccRCC: CAIX(+, diffuse membranous), CK7(−), CD117(−), Cathepsin-K(−), HMB-45(−) ccPRCC: CAIX(+, cup-like pattern), CK7(+), CD117(−), Cathepsin-K(−), HMB-45(−) classic chRCC: CAIX(−), CK7(+, cytoplasmic), CD117(+, membranous), Cathepsin-K(−), HMB-45(−) eAML: CAIX(−), CK7(−), CD117(−), Cathepsin-K(+, cytoplasmic), HMB-45(+, cytoplasmic) MiT-TFE RCC: - Xp11/TFE3: CAIX(+/−, focal), CK7(−), CD117(+/−), Cathepsin-K (+, 50%, cytoplasmic), HMB-45(−) - t[6;11]/TFEB: CAIX(+/−, focal), CK7(−), CD117(−), Cathepsin-K(+, cytoplasmic), HMB-45(+, focal) | 3p loss/deletions or biallelic alteration of VHL gene (3p25) by mutation or hypermethylation (80–98%). ccRCC tumor suppressor genes harbored by 3p locus: KD-M6A (or UTX), KDM5C (or JARID1C), SETD2 and PBRM1. Loss of chromosome 4p, 8p, 9p, 14q. Gain of chromosome 5q. Mutations in BAP1 and PBRM1 genes. FAMILIAL: Von Hippel-Lindau disease; constitutional chromosome 3 translocations. |
Papillary (p) RCC Type 1 | Hypovascular tumor | |||||||
Papillary Component | . Cellularity: small cuboidal cells; uniform, diminished, pale/basophilic cytoplasm; hyperchromatic nuclei, absent nucleoli, lower grade than type 2; foamy macrophages and psammoma bodies are usually encountered. Architecture: single layer of of cells around fibrovascular cores (papillary), tubules and glomeruloid structures. |
CAIX CK7 AMACR Cathepsin-K 34βE12 TFE3/TFEBPOSITIVE | : PAX8; CK7 (diffuse, but strong); EMA (polarized expression); AMACR; AE1/AE3; CD10. NEGATIVE: CAIX; GATA3; p63; 34βE12; TFE3/TFEB; Cathepsin-K. |
ccRCC with papillary growth: CAIX(+, membranous), CK7(−), AMACR(−), Cathepsin-K(−), 34βE12(−), TFE3/TFEB(−) pRCC “type I”: CAIX(−), CK7(+), AMACR(+), Cathepsin-K(−), 34βE12(−), TFE3/TFEB(−) pRCC “type II”: CAIX(−), CK7(+/variable), AMACR(+), Cathepsin-K(−), 34βE12(−), TFE3/TFEB(−) ccPRCC: CAIX(+, cup-like pattern), CK7(+, diffuse), AMACR(−), Cathepsin-K(−), 34βE12(−), TFE3/TFEB(−) MiT-TFE RCC: CAIX(variable, focal), CK7(−), AMACR(+), Cathepsin-K(+, 50%), 34βE12(−), TFE3/TFEB(+, but difficult to standardize on automated platforms, requires FISH assays) | SPORADIC: Activating mutations or amplifications of MET proto-oncogene in >80% of sporadic cases. Gains in chromosomes 3, 7, and 17. FAMILIAL: Hereditary papillary renal carcinoma (HPRC). |
|||
pRCC Type 2 | Cellularity: abundant eosinophilic cytoplasm; frequent nuclear atypia with clearly visible nucleoli (usually ISUP grade ≥3) and nuclear grooves; intracytoplasmic hemosiderin; possible areas of clear cytoplasm; less frequent foamy macrophages and psammoma bodies than type 1. Architecture: papillary, with pseudostratified layers of large cells; variable necrosis. |
POSITIVE: PAX8; CD10 | ||||||
Solid growth pattern | CK7 AMACR WT-1 CD57 | ; AMACR; Topoisomerase II alpha. NEGATIVE: CAIX; CK7 (or patchy positive); EMA (or focal positive); p63; |
Solid pRCC “type I” | HMB45; MelanA; Cathepsin-K; 34βE12; GATA3; TFE3/TFEB. | : CK7(+), AMACR(+), WT-1(−), CD57(−) Metanephric adenomaSPORADIC | : Less consistent than type 1. Heterogeneous, losses or gains of chromosomes 1, 3, 4, 5, 6, 8, 9, 10, 11, 15, 18, and 22. NRF-ARE2 pathway amplification. 8q gains and allelic imbalance of 9q13 (prognostic significance). In advanced stages, CDKN2A/B (18%), TERT (18%), NF2 (13%) and FH (13%) are commonly altered. FAMILIAL: FH gene (1q42–43) mutation in HLRCC. |
||
: CK7(−)/isolated cells, AMACR(−), WT-1(+, nuclear), CD57(+) | Wilms’ Tumor: CK7(−)/isolated cells, AMACR(−), WT-1(+, nuclear), CD57(−) | Chromophobe (ch) RCC | Cellularity: sharply defined, pale cells; “plant-like” cell borders (“vegetable cells”); wrinkled and angulated, irregular nuclei, with coarse chromatin (“raisinoid”); frequent bi/multinucleation and perinuclear halo (koilocytic atypia), with rare mitotic figures; Fuhrman/WHO nuclear grading has no prognostic value and is discouraged. 2 types of cellular morphologies: Type 1—large, polygonal cells, hard cell borders, abundant cytoplasm with reticular pattern (classical variant); Type 2—smaller cells with finely granular eosinophilic cytoplasm (predominant in eosinophilic variant). Architecture: confluent, solid growth with nests, sheets or alveoli/trabeculae; minimal stroma, composed of incomplete fibro-vascular septae around solid sheets; minimal vasculature. |
POSITIVE: PAX8; Hale colloidal iron (histochemical stain; diffuse and strong, reticular); CK7 (diffuse and strong); CD117 | ||||
Cytoplasmic Eosinophilia |
CD117 CK7 Ksp-cadherin HMB-45 Cathepsin-K | (membranous); Ksp-cadherin (+/−); GATA3(+/−); E-cadherin; claudin7 (distal nephron marker); EMA (diffuse cytoplasmic); LMWCK (CK8/CK18); RCCm; CD10; Parvalbumin (calcium binding protein); Cytochrome c oxidase; DOG1; Progesteron Receptor (90% of cells); PDL1 22C3 (in a minority of cases). NEGATIVE: Vimentin (or weak); CAIX; AMACR; N-cadherin; Cathepsin-K; HMB-45; low Ki67 labeling index; |
Oncocytoma | Cyclin D1. | : CD117(+, membranous), CK7(−), Ksp-cadherin(+), HMB-45(−), Cathepsin-K(−) Eosinophilic chRCC: CD117(+, membranous), CK7(+, but variable), Ksp-cadherin (+, mostly), HMB-45(−), Cathepsin-K(−) Oncocytic PRCCSPORADIC | : Multiple losses of whole chromosomes: 1, 2, 6, 10, 13, 17, 21 or Y. DNA rearrangement breakpoints within the TERT promoter region. Mutated TP53 and PTEN in 10–30% of cases (TCGA cohort) and NRAS, mTOR and TSC1/TSC2 in ~5%. Mutations in mitochondrial DNA most commonly affect MT-ND5, with increased expression of genes encoding Krebs cycle enzymes. FAMILIAL: Birt-Hogg-Dube (BHD) syndrome—FLCN gene mutation (17p11.2) |
||
: CD117(−), CK7(+, focal), Ksp-cadherin (unknown), HMB-45(−), Cathepsin-K (unknown) | Oncocytic AML: CD117(−), CK7(−), Ksp-cadherin(−), HMB-45(+, focal), Cathepsin-K(−) | Clear Cell Papillary (ccp) RCC | Cellularity | |||||
Sarcomatoid growth pattern | : clear cytoplasm; characteristic linear arrangement of nuclei away from the basal aspect of cells; low nuclear grade (Fuhrman grade 1–2). Architecture: variable mixture of cystic, branched tubular, solid and papillary components; papillae often tightly packed into anastomosing clear cell ribbons or projecting into cystic spaces; fibrous capsule and variable amounts of hyalinized or sclerotic stroma that may separate the tumor into nodules; never encountered: foamy macrophages, vascular invasion, oxalate crystals, necrosis. |
Vimentin CAIX PAX8 CK7 34βE12 GATA3 p63POSITIVE | : PAX8; CK7 (strong and diffuse); CAIX (diffuse membranous or characteristic “cup shaped” distribution—lack of staining along luminal aspect); AE1/AE3; CAM 5.2; Vimentin; EMA; GATA3 (+/−); 34βE12. |
ccRCC | NEGATIVE: AMACR; CD10; RCCm; TFE3/TFEB; low PCNA; CD117; Cathepsin-K; HMB-45. | : Vimentin(+), CAIX(+) membranous, PAX8(+), CK7(−), 34βE12(−), GATA3(−), p63(−) | No specific genomic imbalances. Lacks genetic modifications of classic pRCC (no +7/+17 or -Y) and/or classic ccRCC (no -3/-3p). Activation of hypoxia inducible factor (HIF) pathway, with underexpressed VHL transcripts, but without typical VHL mechanism (no VHL gene mutations/promoter hypermethylation). May appear in VHL disease. |
|
pRCC | : Vimentin(+), CAIX(−), PAX8(+), CK7(focal/-), 34βE12(−), GATA3(−), p63(−) chRCC: Vimentin(+), CAIX(−), PAX8(+), CK7(+), 34βE12(−), GATA3(−), p63(−) MTSC: Vimentin(+), CAIX(−), PAX8(+), CK7(+), 34βE12(variable), GATA3(−), p63(−) Urothelial: Vimentin(+), CAIX variable/mostly(−), PAX8 mostly(−), CK7(+), 34βE12(+), GATA3(+), p63(+) Sarcoma: Vimentin(+), CAIX(−), PAX8(−), CK7(−), 34βE12(−), GATA3(−), p63(−) |
Collecting duct carcinoma (CDC) | Cellularity: irregular channels, lined with high-grade cuboidal to hobnail cells, with eosinophilic cytoplasm; pleomorphic kariomegaly, with visible nucleoli and coarse chromatin; abundant mitosis. Architecture: the tumor is complex, infiltrative, and poorly circumscribed, composed of cords, tubules, tubulopapillary or tubulocystic structures, within an inflammatory-desmoplastic stroma; intracytoplasmic/intraluminal mucin, microcystic changes from dilation of the tubular structures and sarcomatoid transformation may be present. Tumor-adjacent tubular epithelium, lining collecting ducts, may appear dysplastic. |
POSITIVE: PAX8/PAX2; HMWCK ( | ||||
Distal nephron origin | INI-1/BAF47 OCT4 GATA3 PAX8 | 34βE12); LMWCK (CK7, CK8/18, CK19); Ulex europaeus lectins (Ulex-1); peanut lectin agglutinin (PNA); Mucin (strong); Vimentin; | CDC | EMA; S100A1; INI-1/BAF47 retained. NEGATIVE: p63; Uroplakin II; CD10; AMACR; E-cadherin; CAIX; OCT3/4; CD117; GATA3. |
Lacking loss of 3p or trisomies 7 and 17. HER2/neu amplifications in 45% of cases. Genomic alterations in NF2 (29%), SETD2 (24%), SMARCB1 (18%) and CDKN2A (12%). Recurrent somatic single nucleotide variants in ATM, CREBBP, PRDM1, CBFB, FBXW7, IKZF1, KDR, KRAS, NACA, NF2, NUP98, SS18, TP53 and ZNF521. SLC7A11 (cisplatin resistance associated gene), overexpressed in 80% of cases. | |||
: INI-1/BAF47 (+, and—in 15%), OCT4(−), GATA3(−), PAX8(+) | RMC: INI-1/BAF47 (−), OCT4(+), GATA3(−), PAX8(+) Urothelial: INI-1/BAF47 (+), OCT4(−), GATA3(+), PAX8(−, but + in 20%) |
Renal medullary carcinoma (RMC) | Cellularity: cohesive groups of pleomorphic tumor cells, with vacuolated eosinophilic cytoplasm, that often displaces or indents the hyperchromatic, enlarged nuclei; nuclear membranes are often irregular, with coarse or vesicular chromatin and prominent nucleoli; rhabdoid traits are frequent; abundant intratumoral neutrophils and lymphocytes at tumor rim; abundant sickled erythrocytes (drepanocytes) may be pathognomonic. Architecture: multiple distinct morphologic patterns—reticular; microcystic and adenoid cystic-like; tubular, glandular, tubulopapillary and solid (overlapping with CDC patterns); hemorrhagic and geographic necrosis; angiolymphatic invasion, desmoplastic stroma and infiltrative borders. |
POSITIVE: CAM 5.2; AE1/AE3; CK7/CK20 (may be variable); Vimentin; EMA and CEA; p53; PAX8; OCT3/4; Ulex-1 (focally positive in a minority of cases); vascular endothelial growth factor (VEGF) and hypoxia inducible factor (HIF) may be strongly positive. NEGATIVE: Loss of INI-1/BAF47 expression; colloidal iron; PAS; desmin; 34βE12; GATA3 |
Prevalent loss of SMARCB1/INI1, a major driving feature, identifiable by IHC. Hypoxia inducible factor and VHL abnormalities. ALK rearrangement with vinculin (VCN) fusion. DNA topoisomerase II amplification. Rarely, vinculin—ALK fusion (young patients, less aggressive). Associated with sickle cell trait (monosomy 11—beta globin gene is at end of 11p). |
|||
Succinate dehydrogenase deficient renal (SDHD) RCC | Cellularity: flocculent, pale, eosinophilic, cytoplasmic vacuolation, with a wispy/bubbly appearance and low grade nuclei, with smooth nuclear contours and fine chromatin, with no nucleoli, represents a characteristic finding and must be present at least focally. Architecture: well circumscribed tumor or with a “pushing” border, commonly entrapping tubules; solid, nested or tubular growth pattern with scattered cysts containing eosinophilic material; necrosis, sarcomatoid change and areas with higher grade nuclei may also be present; variant morphologies have been rarely reported. Shares features with chRCC, oncocytoma, ccRCC and pRCC type 2. |
POSITIVE: PAX8; focal pancytokeratin and CAM 5.2; EMA. NEGATIVE: Loss of SDHB IHC staining (indicates disruption of the mitochondrial complex 2 for any reason, not just SDHB gene mutation and caution regarding overinterpretation of negativity in tumors with very clear cytoplasm is essential); CK7; CK20; AE1/AE3; CAIX; RCCm; CD117 (mast cells only); Vimentin; S100A1; TFE3/TFEB; neuroendocrine markers; minimal AMACR staining. |
Wild-type VHL, PIK3CA, AKT, mTOR, MET or TP53 genes. Genes for succinate dehydrogenase subunits (SDH-A, -B, -C, -D), encode protein components of mitochondrial complex II, linking the Krebs cycle with the electron transport chain, being involved in most cases of SDHD RCC. Germline mutations of SDH-A, SDH-B (1p36.13), SDH-C (1q23.3), SDH-D(11q23.1), SHDAF2, determining double hit inactivation, leads to dysfunction of mitochondrial complex II, increased oxidative stress, genomic injury and HIF1α stabilization. |
|||||
Microphtalmia family translocation (MiT) RCC—Xp11/t(6;11) | Cellularity: voluminous cytoplasm and high-grade nuclei, with frequent psammoma bodies and occasional melanin pigment, similar to a pigmented perivascular epithelioid tumor—(PEC)coma. t(6:11) rearranged carcinomas are characteristically biphasic, with small cells clustered around basement membrane material (reminiscent of Call-Exner bodies in adult granulosa cell tumor) and larger epithelioid cells. Architecture: usually papillary and solid alveolar growth pattern, composed of clear to eosinophilic, discohesive pseudostratified cells. |
POSITIVE: TFE3/TFEB (strong nuclear staining, but difficult to standardize on automated platforms; FISH assays are more reliable)—weak TFE3 staining in adults may not be specific; PAX8; Cathepsin-K (~50%, cytoplasmic); CD10; AMACR; Vimentin; E-cadherin; melanocytic markers (HMB45 and MelanA), are common for t(6:11) carcinomas, but always focal, and infrequent for Xp11, which usually manifest variable CD117. NEGATIVE: Variable cytokeratin (only 30–50% positive, less than other RCC types) and EMA (50%, frequently only focal); CAIX usually negative except areas of necrosis; CK7; 34βE12; CD45; calretinin; smooth muscle actin. |
Fluorescence in situ hybridization (FISH) with a TFE3/TFEB breakapart probe is highly sensitive and specific, offering the final diagnosis when morphology and IHC are inconclusive. The TFE3 gene (on Xp11) has been reported to have multiple translocation gene partners, most commonly, ASPL (17q25) and PRCC (1q21), and less commonly NONO (Xq12), PSF/SFPQ (1p34), CLTC (17q23). t(6;11)(p21;q12), a translocation between TFEB and MALAT1 genes, results in overexpression of TFEB. t(X;17)(p11.2;q25), with balanced translocation of TFE3 gene at Xp11.2 and ASPL gene at 17q25, is present in renal neoplasms, whereas in alveolar soft part sarcoma, this translocation is unbalanced, der(17)t(X;17)(p11.2;q25). Melanotic Xp11 RCC and PSF/SFPQ-TFE3 (PEComa), may share the same genetic abnormalities. |
|||||
Acquired cystic disease-associated (ACDA) RCC | Cellularity: moderately cellular, papillary clusters of polygonal to columnar cells with abundant eosinophilic granular cytoplasm, round and central nuclei, finely granular chromatin, prominent, central, grade 3 nucleoli; sometimes with prominent clear cell cytology. Architecture: cribriform, microcystic or sieve-like layout; intratumoral calcium oxalate crystals are very common, but not mandatory for diagnosis; nodules arising from cyst walls or masses separated from cysts may be encountered. |
POSITIVE: No specific IHC profile is required for diagnosis. CD10; AE1/AE3; AMACR; NEGATIVE: EMA; CK7 (but may be focally positive). |
Comparative genomic microarray and FISH studies reveal gains and losses of multiple chromosomes. Gains of sex chromosomes and gains of 3, 7, 16, 17, with a high prevalence of gains of Y, 3 and 16, distinguishing ACDA RCC from pRCC, which also has gains in chromosomes 7 and 17. VHL gene alterations. Chromosome 3p deletion. |
|||||
Multilocular cystic clear cell renal neoplasm of low malignant potential (MCLMP) RCC | Cellularity: single layer of clear cells lining thin fibrous septae or in small clusters; low grade nuclei without nucleoli (ISUP grade 1–2); bland clear cells in septa may be mistaken for lymphocytes (vascularity is important). Architecture: cyst lining may be denuded and, in rare cases, cyst lining may be multilayered, with granular cytoplasm cells and small intracystic papillations; septa may contain calcification or ossification; no expansile growth of clear tumor cells/solid nodules; no necrosis, vascular invasion or sarcomatoid change. |
POSITIVE: PAX8/PAX2; CA IX; EMA; variable CK7. NEGATIVE: AMACR (negative in 80% of cases). |
Genetically related to ccRCC, with 74% of cases demonstrating 3p loss and VHL mutations identified in 25%. | |||||
Tubulocystic (TC) RCC |
Cellularity: tubules/cysts are lined by a single layer of flattened, cuboidal or columnar cells; hobnailing may be present, with modest to abundant amounts of eosinophilic cytoplasm, resembling oncocytoma cell; uniform, round nuclei, with distinct nucleoli (ISUP grade 3); minimal mitotic activity and atypia; very rare necrosis. Architecture: mixture of closely packed tubules and variably sized cysts, with overall low-grade morphology; cysts are separated by fibrous septa; no desmoplasia or cellular stroma; frequently associated with papillary cell neoplasms. |
POSITIVE: CK7; AMACR; Vimentin; EMA; PAX8; fumarate hydratase (FH); Mucin; keratins (AE1/AE3, Cam 5.2, CK8/18, CK19); variable 34βE12; CD10. NEGATIVE: 2 succino-cysteine, CA IX and CD117. |
Distinct molecular signature from other RCCs. Frequently, gains of chromosomes 7 and 17, and loss of Y, similar to pRCC. Mutations in 14 different genes have been documented by targeted, next generation sequencing, most frequently (60% of cases) in ABL1 and PDFGRA genes. |
|||||
Mucinous tubular and spindle cell (MTSC) RCC | Cellularity: relatively uniform, bland, low-grade cuboidal cells, with round to oval nuclei and focally vacuolated, eosinophilic cytoplasm, within strands of metachromatic stromal tissue, which transition into anastomosing spindle cells; may present clear cells and focal clusters of foamy macrophages; rare high-grade nuclei may be present. Architecture: well circumscribed epithelial tumor, partially surrounded by a rim of compressed fibrous tissue; long tubular/cord-like growth pattern; myxoid and bubbly stroma, with abundant extracellular mucin, highlighted by Alcian blue (although some cases may be mucin poor); may manifest well-formed papillae, necrosis, rarely neuroendocrine differentiation or sarcomatoid change; usually, infiltrative growth, desmoplasia, inflammation, hobnail epithelium, and/or cysts are not encountered. |
POSTIVE: PAX2/PAX8; EMA (95%); AMACR (93%); AE1/AE3; E-cadherin; LMWCK: CK7 (81%); CK 8/18; CK19; Neuron Specific Enolase (NSE) and either Chromogranin or Synaptophysin. Histochemical stains: Periodic Acid-Schiff (PAS) (basal lamina around tubules), Alcian blue (mucin). Occasionally, HMWCK: 34βE12 (15%); vimentin; Ulex or CD10 (15%). NEGATIVE: CA IX (positive next to necrosis or focal cytoplasmatic in high-grade areas); GATA3; p63; RCCm (positive in 7%); Villin; Ki67 (<1%). |
Seemingly lacking the characteristic genetic modifications of classic pRCC (trisomies of chromosomes 7/17 or loss of chromosomes Y). Usually hypodiploid, with multiple chromosomal losses (-1, -4, -6, -8, -9, -13, -14, -15, -22), even hypertriploid in some cases, but with no identifiable pattern. |
|||||
Hybrid oncocytic-chromophobe (HOCh) RCC | Cellularity: usually, dual population of eosinophilic cells—oncocytic (medium sized, round cell, with granular eosinophilic cytoplasm and concentric round nucleus, low nuclear:cytoplasmic ratios, prominent nucleolus) and chromophobe (large, polygonal, “plant-like” cell, with a distinct cell membrane, containing flaky eosinophilic cytoplasm, often with a perinuclear halo and an irregular “raisinoid” wrinkled nucleus), with a third cell subtype, manifesting overlapping cytonuclear features of both oncocytic and chromophobe morphology, being sometimes encountered; mitotic rate is very low. Architecture: well circumscribed, non-infiltrative, intrarenal tumor, with a solid alveolar and cystic architecture; may manifest vascular invasion and, rarely, necrosis. |
POSITIVE: CK7 (may be focal); AE1/AE3; Parvalbumin; Antimitochondrial Antigen; EMA; E-cadherin (most); CD117; S100A1; CD82; Vimentin (few cases); Hale colloidal iron (stains apical/luminal oncocytic cells and, often, intracytoplasmic in chromophobe cells. NEGATIVE: AMACR; CK20; CD10 and CA IX. |
SPORADIC: May present numerous molecular anomalies (both mono- and polysomies) of chromosomes 1, 2, 6, 9, 10, 13, 17, 21, and 22. Lack of mutations in the VHL, c-kit, PDGFRA, and FLCN genes. FAMILIAL: May be associated with BHD, autosomal dominant syndrome, characterized by a genetic abnormality on chromosome 17p11.2, leading to a mutation in the FLCN gene. |
Predominant Morphological Trait |
Specific Panel | Entities Entering Differential Diagnosis with Corresponding IHC Profiles |
---|