COW-2020-23

CASE OF THE WEEK

2020-23 / June 8
(Contributor: Daniel H. Russell)

A 4 month-old boy with an unremarkable past medical history presented with a 9.0 cm renal mass. The patient was radiographically diagnosed and underwent 5 weeks of pre-surgical chemotherapy.

Quiz

1. What is the diagnosis?

a. Congenital Mesoblastic Nephroma, cellular variant

b. Wilms Tumor, stromal predominant

c. Clear Cell Sarcoma

d. Malignant Rhabdoid Tumor

e. Intrarenal Yolk Sac Tumor

 

2. What immunohistochemical stain could be helpful in confirming the diagnosis (via positive expression)?

a. desmin

b. WT1

c. cyclin D1

d. INI1

e. AFP


3. What molecular aberration is characteristic in this tumor?

a. t(12;15)

b. mutations involving WT1

c. internal tandem repeats in BCOR

d. SMARCB1 mutation (INI1 loss)

e. loss of heterozygosity

1. c
2. c
3. c

1. Clear Cell Sarcoma
2. cyclin D1
3. internal tandem repeats in BCOR

Clear cell sarcoma of kidney (CCSK) is an infrequent pediatric renal tumor, comprising approximately 3% of all pediatric renal cancers with a mean age of diagnosis of 3 years. Grossly, tumors are bulky, gray, fish-fleshy masses which bulge from the cut surface. Histologically, tumor cells are euchromatic or hypochromatic with rare mitoses and abundant clear to gray cytoplasm. The classic pattern is a tumor which grows in nests embedded in a vascular rich (chicken wire-like) background. Architecturally, a variety of patterns can be seen in CCSK including classic (90% of cases), sclerosing (35%), myxoid (30-50%), cellular (25%), epithelioid (15%), palisading (10%), spindle cell (8%), storiform (7%), and anaplastic (2%). Immunohistochemistry can be helpful in supporting the diagnosis, as CCSK expresses cyclin D1, CD10, BCL-2, and BCOR, and lacks expression with CD34, S100, desmin, SMA, CD99, keratins and EMA, chromogranin, and synaptophysin. The most common molecular aberration characteristic of CCSK is internal tandem duplication of the last exon encoding BCL6 corepressor (BCOR), resulting in overexpression of the protein in 90% of cases. Other aberrations include BCOR fusions with CCNB3 and t(10;17) which fuses YWHAE and NTUM2.

Congenital mesoblastic nephroma (CMN) should be considered in all patients with renal tumors under 6 months of age. There are two morphologically and molecularly distinct variants of CMN, classic and cellular. Cellular CMN is a monotonous tumor composed of spindled cells with a storiform growth pattern and is characterized by t(12;15) which fuses ETV6 to NTRK3. Cellular CMN does not express BCOR, while CCSK is negative for desmin and lacks t(12;15). Neither form of CMN contains a growth pattern which compares to the classic vascular rich pattern of CCSK. Certain patterns of CCSK can on occasion mimic stromal or blastemal predominant Wilms’ Tumor, particularly if fixation is suboptimal resulting in rounding of CCSK nuclei, loss of cytoplasmic volume, and clumping of chromatin. Nuclei of the former are hyperchromatic, mitotically active, and contain clumped granular chromatin, whereas nuclei of CCSK are euchromatic and bland. A helpful technique is to look at the slide grossly. If the slide is bright pink/amphophilic opposed to areas of dark blue, the diagnosis is more likely Wilm’s Tumor; if the slide is gray or pale blue, CCSK should be considered. In challenging cases, BCOR, cyclin D1, WT1, and CD99 are helpful, as CCSK expresses BCOR and cyclin D1 and lacks expression with WT1 and CD99, while Wilms’ Tumor has the reverse profile. Malignant rhabdoid tumor is a universally lethal cancer that presents at high stage and is characterized by deletion of 22q11 which results in inactivation of INI1, a fact which can be exploited using immunohistochemistry (absence of staining is “positive” and represents mutation pattern aberrancy). Morphologically, malignant rhabdoid tumors are high grade tumors with peripherally placed round to polyhedral nuclei and a characteristic cytoplasmic inclusions, which imparts the rhabdoid character. The nuclei contain prominent nucleoli and vesicular chromatin. In a poorly fixed specimen, the rhabdoid nature of the tumor is lost and confusion with cellular CMN is possible. INI1 immunohistochemistry can be helpful in resolving challenging cases. Primary renal yolk sac tumors (YST) are exceedingly rare. Both CCSK and YST are known for architectural heterogeneity with numerous growth patterns, but YST have a more primitive nuclear appearance which is hyperchromatic with granular chromatin and usually lacks the abundant cytoplasm of CCSK. AFP and glypican-3 can be employed to discriminate challenging cases, as CCSK lacks expression with both, while YST lacks BCOR aberrancy. FISH for i12p is unhelpful in confirming YST of pre-pubertal children and is not of discriminatory benefit in this setting.

1. Argani P, Perlman EJ, Breslow NE, Browning NG, Green DM, D’Angio GJ, Beckwith JB. Clear cell sarcoma of the kidney: a review of 351 cases from the National Wilms Tumor Study Group Pathology Center. Am J Surg Pathol. 2000 Jan;24(1):4-18.

2. Ueno-Yokohata H, Okita H, Nakasato K, Akimoto S, Hata J, Koshinaga T, Fukuzawa M, Kiyokawa N. Consistent in-frame internal tandem duplications of BCOR characterize clear cell sarcoma of the kidney. Nat Genet. 2015 Aug;47(8):861-863.

3. Argani P, Pawel B, Szabo S, Reyes-Múgica M, Timmons C, Antonescu CR. Diffuse strong BCOR immunoreactivity is a sensitive and specific marker for clear cell sarcoma of the kidney (CCSK) in pediatric renal neoplasia. Am J Surg Pathol. 2018 Aug;42(8):1128-1131.

Daniel H. Russell
Tripler Army Medical Center
russdanny22@gmail.com

Kidney

BCOR, Clear Cell Sarcoma of Kidney, CCNB3, Congenital Mesoblastic Nephroma, CCSK