cyclin-d1 and Sarcoma--Clear-Cell

Clear cell melanoma is a rare clear cell malignancy. Accurate diagnosis of clear cell melanoma requires integration of immunohistochemical and morphologic findings, with molecular studies to rule out clear cell sarcoma. The differential diagnosis includes melanoma, carcinoma, perivascular epithelioid cell tumor, and epidermotropic clear cell sarcoma. We use a case of a lesion on the helix of an 86-year-old man as an example. Histologic examination revealed an ulcerated clear cell malignant tumor. Tumor cell cytoplasm contained periodic acid-Schiff-positive, diastase-sensitive glycogen. Tumor cells showed positive labeling for S100, HMB-45, and Melan-A, and negative labeling for cytokeratins, p63, and smooth muscle actin. Molecular studies demonstrated BRAF V600E mutation, copy gains at the 6p25 (RREB1) and 11q13 (CCND1) loci, and absence of EWSR1-ATF1 fusion. These findings supported a diagnosis of clear cell melanoma. The rare pure clear cell morphology occurs due to accumulation of intracytoplasmic glycogen. We review the differential diagnosis of clear cell melanoma and describe the utility of immunohistochemical and molecular studies in confirming this diagnosis.

Topics: Aged, 80 and over; Amino Acid Substitution; Biomarkers, Tumor; Cyclin D1; Diagnosis, Differential; DNA-Binding Proteins; Ear Auricle; Gene Dosage; Glycogen; Humans; Male; Melanoma; Mutation; Perivascular Epithelioid Cell Neoplasms; Proto-Oncogene Proteins B-raf; Sarcoma, Clear Cell; Skin; Skin Neoplasms; Transcription Factors; Up-Regulation

Pediatric renal tumors overlap histomorphologically and may cause misdiagnosis. We aimed to determine the role of immunohistochemical staining of Cyclin D1, PTEN, beta-catenin and PDGFR-alpha on pediatric renal tumors.. Thirty-six cases of 8 different tumors were included in the study. Four blocks of paraffin tissue microarray were constructed. Cyclin D1, PTEN, beta-catenin and PDGFR-alpha were used in all cases. Staining intensity and extent were graded.. All cases of clear cell sarcoma (CCS) and epithelial components of Wilms tumor (WT) showed immunopositivity for Cyclin D1 but blastemal and stromal components of WT were negative. All cases of CCS and most cases of WT consisting of blastemal and stromal components demonstrated loss of expression with PTEN.. Cyclin D1 is not a specific immunohistochemical marker due to its strong and diffuse positivity in CCS cases. It may be useful to differentiate CCS from blastemal and stromal components of WT. Other markers except cyclin D1 do not have a role in the differential diagnosis.

Topics: beta Catenin; Biomarkers, Tumor; Child; Cyclin D1; Diagnosis, Differential; Female; Humans; Immunohistochemistry; Kidney Neoplasms; Male; PTEN Phosphohydrolase; Receptor, Platelet-Derived Growth Factor alpha; Sarcoma, Clear Cell; Wilms Tumor

Clear cell sarcoma of kidney (CCSK) is the second most common pediatric renal malignancy, constituting ∼3% of renal tumors. Due to its morphologic diversity, the diagnosis of CCSK is often challenging. Recent studies have identified internal tandem duplication of BCL6 corepressor (BCOR) gene in CCSKs which coupled with cyclin D1 immunoreactivity, is helpful in differentiating it from its mimics, particularly blastema-rich Wilms tumor (WT), malignant rhabdoid tumor (MRT), and congenital mesoblastic nephroma (CMN). We aimed to evaluate the utility of cyclin D1 and BCOR immunohistochemistry in differentiating CCSK from its morphologic mimics.. Our cohort comprised of 38 pediatric renal tumors which included CCSK (n=18), WT (n=10), MRT (n=5), and CMN (n=5) cases. A detailed clinicopathologic analysis was performed, and tissue microarray were constructed for CCSK and WT, while MRT and CMN tumors were individually stained.. The age ranged from 2 months to 16 years with male:female ratio of 3:1. Strong, diffuse nuclear immunoreactivity for cyclin D1 and BCOR was noted in 61% (n=11/18) and 83% (n=15/18) of CCSK, respectively, while it was significantly less in WT (n=3/10 for cyclin D1) (n=2/10 for BCOR). None of the MRT and CMN examples demonstrated any immunoreactivity. Interestingly, only the blastemal component of WTs showed distinct, rare nuclear immunoreactivity for cyclin D1 or BCOR and the combination of these was never positive in a given case.. Our results provide evidence that concurrent immunopositivity with cyclin D1 and BCOR is helpful in distinguishing CCSK from its morphologic mimics.

Topics: Adolescent; Biomarkers, Tumor; Child; Child, Preschool; Cyclin D1; Diagnosis, Differential; Female; Follow-Up Studies; Humans; Immunohistochemistry; Infant; Kidney Neoplasms; Male; Nephroma, Mesoblastic; Prognosis; Proto-Oncogene Proteins; Repressor Proteins; Rhabdoid Tumor; Sarcoma, Clear Cell; Wilms Tumor

Clear cell sarcoma of the kidney (CCSK) is a rare malignant pediatric renal neoplasm with a heterogeneous histological appearance which often results in misdiagnosis. There are no specific immunohistochemical markers which can help in differentiating CCSK from other pediatric renal neoplasms. Recently Cyclin D1 has been investigated as a possible marker in this regard. In this study, we aim to determine the usefulness of Cyclin D1 in differentiating between CCSK and other pediatric renal neoplasms and to compare our results with those of recently published studies.. A total of 48 cases of CCSK, Wilms tumor (WT), renal rhabdoid tumor, mesoblastic nephroma, renal Ewing sarcoma and neuroblastoma were included in the study. All cases were stained with cyclin D1. Extent of Cyclin D1 staining was graded according to percentage of positive tumor cells as diffuse (> 70%), focal (5 to 70%), and negative (< 5%). Intensity of Cyclin D1 staining was graded as strong or 3+, moderate or 2+ and weak or 1 + .. Most or all cases of CCSK, neuroblastoma and renal Ewing sarcoma demonstrated diffuse and strong positivity for Cyclin D1. Most cases of Wilms tumor (epithelial component) also demonstrated diffuse and often strong positivity for Cyclin D1. In most cases of WT, blastemal component was negative.. Cyclin D1 is a sensitive but not specific immunohistochemical marker for CCSK and many other pediatric renal malignant neoplasms as well as for neuroblastoma. Hence, careful examination of histological features is important in reaching an accurate diagnosis in CCSKs. However, Cyclin D1 is very helpful in distinguishing between blastema-rich WT and CCSK.

Topics: Adult; Biomarkers, Tumor; Child, Preschool; Cyclin D1; Female; Humans; Infant; Kidney Neoplasms; Male; Sarcoma, Clear Cell; Young Adult

Topics: Adolescent; Child; Cyclin D1; Humans; Sarcoma, Clear Cell; Sarcoma, Ewing

Topics: Adolescent; Child; Cyclin D1; Humans; Sarcoma, Clear Cell; Sarcoma, Ewing

Distinguishing clear cell sarcoma of the kidney (CCSK) from other paediatric malignancies, particularly blastema-rich Wilms tumour (WT) and congenital mesoblastic nephroma (CMN), is challenging. Specific immunohistochemistry for CCSK does not exist, and diagnosis rests upon histopa thology. Recently, the YWHAE-FAM22 rearrange ment, identical to that in endometrial stromal sarcoma (ESS), has been identified in CCSKs. As this fusion results in overexpression of cyclin D1 in ESS, we postulated that overexpression would also occur in CCSK; cyclin D1 immunohistochemistry could then be used to differentiate CCSK from other tumours. The goal of this study was therefore to evaluate the utility of cyclin D1 immunohistochemistry in identifying CCSK and helping to differentiate it from its mimics.. Cyclin D1 expression was evaluated in 59 renal tumours-CCSK (14), WT (25), rhabdoid tumour (four), Ewing sarcoma (five), and CMN (11)-and four neuroblastomas. All 14 CCSKs showed diffuse and strong reactivity. In contrast, the blastematous component of most WTs showed only rare positive nuclei, that of rhabdoid tumours showed rare to focal immunoreactivity, and that of more than half of CMNs showed weak or focal immunoreactivity. Most Ewing sarcomas and all neuroblastomas showed diffuse moderate to strong staining.. Cyclin D1 is most helpful in distinguishing CCSK from WT, rhabdoid tumour, and some CMNs, but not from neuroblastoma or Ewing sarcomas.

Topics: Biomarkers, Tumor; Child, Preschool; Cyclin D1; Diagnosis, Differential; Female; Humans; Immunohistochemistry; Kidney Neoplasms; Male; Nephroma, Mesoblastic; Neuroblastoma; Rhabdoid Tumor; Sarcoma, Clear Cell; Sarcoma, Ewing; Wilms Tumor