Alterations of the Cell-Cycle Inhibitors p27KIP1 and p16INK4a Are Frequent in Blastic Plasmacytoid Dendritic Cell Neoplasms

Wiesner, Thomas; Obenauf, Anna C.; Cota, Carlo; Fried, Isabella; Speicher, Michael R.; Cerroni, Lorenzo

doi:10.1038/jid.2009.369

Cited by 61 publications

(43 citation statements)

References 13 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The amplification product was purified using the GenElute PCR Clean-up Kit according to the manufacturer's instructions (#NA1020; Sigma-Aldrich) and labeled for aCGH as described previously. 10 As shown previously, no major artifacts were induced by whole-genome amplification and a similar signal-to-noise ratio of the aCGH profile was observed when using amplified or non-amplified DNA. 11 aCGH was performed in all cases in which DNA was available.…”

Section: Dna Extraction and Acghsupporting

confidence: 76%

Histological and genetic evidence for a variant of superficial spreading melanoma composed predominantly of large nests

et al. 2012

Self Cite

View full text Add to dashboard Cite

Cutaneous melanomas are characterized by a range of histological appearances, and several morphological variants have been described. In this study, we report a variant of superficial spreading melanoma that is characterized by large, irregular junctional melanocytic nests. The junctional nests varied in shape and size, showed focal tendency to confluence, and were often surrounded by a cuff of epidermal keratinocytes. The melanocytes comprising the nests showed variable cytological atypia. In most of the cases, scant intraepidermal or junctional single melanocytes were seen, and other well-documented diagnostic criteria for melanoma were lacking, and as a result, histological recognition of these tumors as melanoma was difficult. Some cases were associated with an invasive dermal component or showed evidence of sun damage. To provide supporting evidence for malignancy, we analyzed these tumors for genomic aberrations. Using array comparative genomic hybridization (aCGH), we identified multiple genomic aberrations in all analyzed cases. A similar pattern of genomic aberrations was seen in a control group of bona fide superficial spreading melanomas, suggesting that these 'melanomas composed exclusively or predominantly of large nests' are indeed variants of superficial spreading melanoma. Fluorescence in-situ hybridization (FISH) was positive in 40% of the cases. However, using aCGH, the FISH-negative cases showed multiple genomic aberrations in regions that are not covered by FISH. The low sensitivity of the FISH test can be explained by the fact that FISH only evaluates four genomic loci for aberrations, whereas aCGH surveys the entire genome. In summary, we present histological and molecular genetic evidence for a morphological variant of superficial spreading melanoma. Awareness of the histological features will aid in their correct diagnosis as melanoma, and in difficult cases, judicious application of ancillary tests such as aCGH (rather than FISH) will assist accurate diagnosis. Modern Pathology (2012) 25, 838-845; doi:10.1038/modpathol.2012; published online 2 March 2012 Keywords: chromosomal aberrations; comparative genomic hybridization; fluorescence in-situ hybridization; melanocytic tumors; melanoma Cutaneous melanomas are characterized by a diverse range of histological appearances, and several morphological variants have been described. The most common subtypes in histological classification systems are superficial spreading melanoma, nodular melanoma, lentigo maligna melanoma, and acral lentiginous melanoma. 1 Although histological evaluation is a reliable means of accurately classifying melanocytic tumors as benign

show abstract

Section: Dna Extraction and Acghsupporting

confidence: 76%

Histological and genetic evidence for a variant of superficial spreading melanoma composed predominantly of large nests

et al. 2012

Self Cite

View full text Add to dashboard Cite

show abstract

“…Slides were scanned using Agilent's microarray scanner G2505B and analyzed using the Agilent Feature Extraction and DNA Workbench software 6.5.018. 16 Eight cases of classical dermatofibroma, which had been analyzed previously, and two small typical cases of cellular dermatofibromas were used as negative controls for aCGH and showed no genomic aberrations (data not shown). As positive control for aCGH, we used a dermosubcutaneous metastasis from the chest wall of a 62-year-old male patient, to whom 6 years earlier a 'fibrohistiocytic sarcoma' had been excised on his lateral neck.…”

Section: Methodsmentioning

confidence: 98%

Malignant dermatofibroma: clinicopathological, immunohistochemical, and molecular analysis of seven cases

et al. 2013

Self Cite

View full text Add to dashboard Cite

Dermatofibroma (cutaneous fibrous histiocytoma) represents a common benign mesenchymal tumor, and numerous morphological variants have been described. Some variants of dermatofibroma are characterized by an increased risk of local recurrences, and there are a few reported metastasizing cases. Unfortunately, an aggressive behavior cannot be predicted reliably by morphology at the moment, and we evaluated the value of array-comparative genomic hybridization (CGH) in this setting. Seven cases of clinically aggressive dermatofibromas were identified, and pathological and molecular features were evaluated. The neoplasms occurred in four female and in three male patients (mean age was 33 years, range 2-65 years), and arose on the shoulder, buttock, temple, lateral neck, thigh, ankle, and cheek. The size of the neoplasms ranged from 1 to 9 cm (mean: 3 cm). An infiltration of the subcutis was seen in five cases. Two neoplasms were completely excised, whereas an incomplete or marginal excision was reported in the remaining cases. Local recurrences were seen in six cases (time to the first recurrence ranged from 8 months to 9 years). Metastases were noted between 3 months and 8 years after diagnosis in six patients. Two patients died of disease, and two patients are alive with disease. Histologically, the primary tumors showed features of cellular dermatofibroma (four cases), cellular/ aneurysmal dermatofibroma (one case), atypical/cellular dermatofibroma (one case), and classical dermatofibroma (one case). Mitotic figures ranged from 3 to 25 per 10 high-power fields, and focal necrosis was present in five cases. Interestingly, malignant transformation from cellular dermatofibroma to an obvious spindle cell/ pleomorphic sarcoma was seen in one primary and in one recurrent neoplasm. Five neoplasms showed chromosomal aberrations by array-CGH, suggesting that these changes may represent an additional diagnostic tool in the recognition of cases of dermatofibroma with a metastatic potential.

show abstract

“…Structural abnormalities in 12p are among the most common, corresponding to a loss of the CDKN1B locus reported in more than 60% of patients with BPDCN. 10,31,32 Dysregulation of CDKN1B and its gene product p27 have been implicated in the pathogenesis of multiple malignancies. In a series of 21 patients with BPDCN, biallelic loss of 9p21.3 and the CDKN2A/CDKN2B genes encoding p16 and cyclin-dependent kinase inhibitors results in a poorer overall survival (OS) compared with wild-type patients.…”

Section: Geneticsmentioning

confidence: 99%

Treatment of blastic plasmacytoid dendritic cell neoplasm

Sullivan

Rizzieri

2016

Hematology

View full text Add to dashboard Cite

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare myeloid malignancy with no defined standard of care. BPDCN presents most commonly with skin lesions with or without extramedullary organ involvement before leukemic dissemination. As a result of its clinical ambiguity, differentiating BPDCN from benign skin lesions or those of acute myeloid leukemia with leukemia cutis is challenging. BPDCN is most easily defined by the phenotype CD4 1 CD56 1 CD1231 lineage -MPO -, although many patients will present with variable expression of CD4, CD56, or alternate plasmacytoid markers, which compounds the difficulty in differentiating BPDCN from other myeloid or lymphoid malignancies. Chromosomal aberrations are frequent, and the mutational landscape of BPDCN is being rapidly characterized although no obvious molecular target for chemoimmunotherapy has been identified. Chemotherapy regimens developed for acute myeloid leukemia, acute lymphoid leukemia, and myelodysplastic syndrome have all been used to treat BPDCN. Relapse is frequent, and overall survival is quite poor. Allogeneic transplantation offers a chance at prolonged remission and possible cure for those who are eligible; unfortunately, relapse remains high ranging from 30% to 40%. Novel therapies such as SL-401, a diphtheria toxin conjugated to interleukin-3 (IL-3) is commonly overexpressed in BPDCN and other aggressive myeloid malignancies and has shown considerable promise in ongoing clinical trials. Future work with SL-401 will define its place in treating relapsed or refractory disease as well as its role as a first-line therapy or bridge to transplantation. Learning Objectives• To understand the clinical and laboratory approach for differentiating BPDCN from acute myeloid leukemia with cutaneous manifestations • To consider appropriate first-line and salvage treatments for BPDCN, including the utility of hematopoietic allogeneic stem cell transplantation and novel agents in various patient populations

show abstract

Alterations of the Cell-Cycle Inhibitors p27KIP1 and p16INK4a Are Frequent in Blastic Plasmacytoid Dendritic Cell Neoplasms

Cited by 61 publications

References 13 publications

Histological and genetic evidence for a variant of superficial spreading melanoma composed predominantly of large nests

Histological and genetic evidence for a variant of superficial spreading melanoma composed predominantly of large nests

Malignant dermatofibroma: clinicopathological, immunohistochemical, and molecular analysis of seven cases

Treatment of blastic plasmacytoid dendritic cell neoplasm

Contact Info

Product

Resources

About