Bruno E. Paredes

Angioinvasive lymphomatoid papulosis: a new variant simulating aggressive lymphomas.

Lymphomatoid papulosis (LyP) belongs to the spectrum of primary cutaneous CD30-positive lymphoproliferative disorders. Clinically, LyP is characterized by a variable number of self-healing papulo-nodular lesions, with the typical waxing and waning course. Histologically, 4 types (A, B, C, and D) have been delineated. Angioinvasive growth and large ulcers are rare findings in LyP and simulate aggressive lymphoma. We retrospectively analyzed the clinicopathologic and molecular features of angioinvasive LyP in a series of 16 patients. This new form of LyP is characterized by oligolesional papules that rapidly ulcerate and evolve into large necrotic eschar-like lesions with a diameter of 1 to 4 cm and an angiocentric and angiodestructive infiltrate of small-sized to medium-sized atypical lymphocytes expressing CD30 and frequently CD8. As in other forms of LyP, the lesions underwent spontaneous regression after a few weeks. Recurrences were common, but the prognosis was excellent with no extracutaneous spread or disease-related deaths. Complete remission occurred in 9 of 16 patients (56%). This LyP variant should be distinguished from aggressive forms of angiocentric and angiodestructive and cytotoxic T-cell lymphomas. We propose the term LyP type E for this clinically and histologically unusual variant.

Plasmacytoid dendritic cells: an overview of their presence and distribution in different inflammatory skin diseases, with special emphasis on Jessner's lymphocytic infiltrate of the skin and cutaneous lupus erythematosus

Background: Plasmacytoid dendritic cells (PDC) play a pivotal role in the induction of autoimmune diseases and other skin diseases. The present study focuses on the distribution patterns of PDC in patients with cutaneous lupus erythematosus (LE) and Jessners lymphocytic infiltrate (LI) of the skin and compares them with other skin diseases. The goal was to scrutinize the involvement of PDC in LI, and to show that PDC present a specific pattern of distribution in various cutaneous disorders.

Plaque-like CD34-positive dermal fibroma ("medallion-like dermal dendrocyte hamartoma"): clinicopathologic, immunohistochemical, and molecular analysis of 5 cases emphasizing its distinction from superficial, plaque-like dermatofibrosarcoma protuberans.

Medallion-like dermal dendrocyte hamartoma (DH) and superficial (plaque-like) dermatofibrosarcoma protuberans (DFSP) are CD34-positive dermal neoplasms with overlapping clinicopathologic features. We analyzed the clinical, histomorphologic, and molecular criteria of 5 DH and 7 DFSP to delineate diagnostically relevant differences between incipient dermal DFSP and its benign look-alike, DH. We expand the clinical and histologic spectrum of DH. As medallion-like dermal DH is neither of dermal dendrocyte lineage nor a genuine hamartoma, we propose instead the descriptive term of plaque-like CD34-positive dermal fibroma (PDF). Both PDF/DH and DFSP presented as slightly pigmented and indurated plaques on neck, trunk, and extremities. Histologically, DFSP was characterized either by horizontally oriented spindle cell fascicles or by diffusely arranged fibroblasts within a slightly myxoid stroma in the upper two-thirds of the dermis, whereas PDF/DH presented with a cellular band-like fibroblastic proliferation mostly in the papillary and adjacent upper reticular dermis. Only one congenital PDF/DH in a 9-year-old boy extended into the septa of the subcutaneous fat. Formalin-fixed paraffin-embedded archival tissue was used for detection of the COL1A1-PDGFB gene rearrangement by multiplex reverse transcription-polymerase chain reaction (RT-PCR) and by dual color fusion fluorescence in-situ hybridization (FISH). Archival blocs older than 4 years did not yield amplifiable RNA because of RNA degradation, whereas FISH analysis was feasible in all investigated cases. FISH analysis revealed COL1A1-PDGFB gene rearrangement in all DFSP cases (n=7), whereas RT-PCR could detect the COL1A1-PDGFB fusion transcript only in 1 DFSP. Two cases were negative. In 4 archival cases with storage between 4.5 and 12 years, RNA had been degraded making these cases unsuitable for RT-PCR. In PDF/DH, both RT-PCR and FISH analysis did not reveal any evidence of COL1A1-PDGFB gene rearrangement. We show that PDF/DH and superficial (plaque-like) DFSP, subtle clinicopathologic differences notwithstanding, are morphologic look-alikes that can be kept apart by molecular studies of the COL1A1-PDGFB gene fusion. For the detection of the COL1A1-PDGFB gene rearrangement in diagnostically difficult cases, RT-PCR and FISH analysis are reliable and helpful diagnostic tools. In archival formalin-fixed paraffin-embedded tissue, however, FISH analysis is more robust and exhibits a higher clinical sensitivity than RT-PCR.

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

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.

A proposal for improving multicolor FISH sensitivity in the diagnosis of malignant melanoma using new combined criteria.

Abstract: Fluorescence in situ hybridization (FISH) for the diagnosis of melanoma makes use of specific fluorescent probes to detect selected chromosomal alterations on paraffin-embedded tissue samples. To date, interpretation of FISH data has been based on numerical values generated by 2 different computational algorithms that of Abbott and that of Gerami. To further evaluate the value of FISH in the diagnosis of malignant melanoma, we selected 163 clinically and histologically unequivocal cases of malignant melanoma in a cohort of 575 melanocytic tumors and analyzed FISH data using the criteria of Abbott, Gerami, and new combined criteria. Depending on the used criteria, FISH was positive in the unequivocal malignant melanoma in 69.3% (113/163) of cases using the Abbott criteria, 74.2% (121/163) of cases using the Gerami criteria, and 82.2% (134/163) of cases using the combined criteria of Abbott and Gerami. Although use of all 3 criteria was associated with 100% FISH negativity in a cohort of 30 unequivocal benign melanocytic nevi, use of the combined criteria revealed more FISH-positive cases in ambiguous benign melanocytic lesions than the criteria of Abbott or Gerami alone: Abbott, 125 of 367; Gerami, 146 of 367; combined, 161 of 367. Furthermore, we show that 66% (8/12) of FISH-negative cases of unequivocal melanoma are positive when analyzed by array comparative genomic hybridization (aCGH), demonstrating that false-negative results remain despite the usage of the combined criteria for evaluation of FISH data. In these 8 FISH-negative aCGH-positive cases, copy number alterations were often located on chromosomes 9p, a chromosomal locus that is not targeted by the FISH probes currently used. In conclusion, the existing criteria for the evaluation of multicolor melanocytic FISH are limited by a nonnegligeable rate of false negativity that can be reduced by using newly proposed combined criteria but at the cost of increased detection of FISH positivity in ambiguous benign melanocytic lesions.

Fumarate hydratase immunohistochemical staining may help to identify patients with multiple cutaneous and uterine leiomyomatosis (MCUL) and hereditary leiomyomatosis and renal cell cancer (HLRCC) syndrome.

Multiple cutaneous and uterine leiomyomatosis (MCUL) also named as hereditary leiomyomatosis and renal cancer syndrome (HLRCC) is an autosomal dominant disorder caused by heterozygotic germline mutations in fumarate hydratase (FH) with incomplete penetrance and clinically challenging to diagnose. To test immunohistochemistry for FH as a potential marker for the detection of FH‐deficiency.

Primary Cutaneous Anaplastic Large Cell Lymphoma with Angioinvasive Features and Cytotoxic Phenotype: A Rare Lymphoma Variant within the Spectrum of CD30+ Lymphoproliferative Disorders

Background: Primary cutaneous anaplastic large cell lymphoma (PCALCL) presents with solitary or grouped exophytic tumors and cohesive infiltrates of large CD30+ T cells. Objective: To report an angioinvasive variant of PCALCL. Methods: Retrospective analysis of clinicopathological features of this variant. Results: The group consisted of six patients (median age 46 years) with a solitary flat necrotic lesion preferentially located on the upper extremity. Histologically, there were angiocentric and angiodestructive infiltrates of medium-sized to large pleomorphic and anaplastic cells co-expressing CD30 and CD8. Five patients were treated with surgical excision and one patient with radiotherapy. A relapse was observed in one patient with spontaneous regression of the lesions suggesting a link to the recently described angioinvasive lymphomatoid papulosis (type E). All patients were alive without evidence of disease after a median follow-up of 31 months (range 15-96), indicating an excellent prognosis. Conclusions: The angioinvasive variant of PCALCL is rare but distinctive and prone to misinterpretation as aggressive lymphoma due to its histological features.

Cutaneous adenodermatofibroma: report of 2 cases.

Dermatofibromas (DFs) are common benign fibrohistiocytic lesions, mostly affecting young adults. Many types of DF have been described, depending on architectural, cellular, and stromal peculiarities. Recently, a peculiar type of benign cutaneous tumor showing hemosiderotic DF-like stroma and apocrine glands has been described. We report 2 additional cases of DF without hemosiderotic changes showing entrapped apocrine glandular structures. We speculate about the origin of the glandular component and propose the term adenodermatofibroma for this type of lesions.

Atypical lipomatous tumor/"well-differentiated liposarcoma" of the skin clinically presenting as a skin tag: clinicopathologic, immunohistochemical, and molecular analysis of 2 cases.

Liposarcomas are extremely rare in the skin. When they involve the skin, it is usually by upward spread from a subcutaneous or deeper seated liposarcoma. Very rarely, liposarcoma metastasize to the skin or arise as a primary dermal lesion. We describe 2 cases of atypical lipomatous tumor “well-differentiated liposarcoma” located in dermis. Both presented clinically as a skin tag. The neoplasms arose in a 56-year-old female and a 69-year-old male patient. Both lesions were treated by excision and reexcision. In addition to classical morphology of atypical lipomatous tumor with evidence of lipoblasts and atypical adipocytes, immunohistochemistry with nuclear murine double-minute type 2 protein and cyclin-dependent kinase-4 expression as well as fluorescence in situ hybridization analysis showing an amplification of murine double-minute type 2 protein and cyclin-dependent kinase-4 were helpful to establish the diagnosis. None of the cases recurred after surgical treatment. These 2 cases show the importance of not to misdiagnose lesions which clinically may appear to be benign.

Contents Vol. 227, 2013

G. Argenziano, Reggio Emilia M. Augustin, Hamburg W.H. Boehncke, Geneve L. Borradori, Bern R.P. Braun, Zürich R. Cerio, London L. Cerroni, Graz O. Chosidow, Créteil A. Dupuy, Rennes J.W. Fluhr, Berlin L. French, Zürich F. Furukawa, Wakayama M. Gilliet, Lausanne A.K. Gupta, London, Ont. R. Happle, Freiburg R.J. Hay, London P. Itin, Basel G. Kaya, Geneva R.G.B. Langley, Halifax, N.S. J.M. Mascaro, Jr., Barcelona K. Matsunaga, Nagoya Y. Miyachi, Kyoto L. Naldi, Bergamo F. Nestle, London C. Paul, Toulouse T. Shiohara, Tokyo Th. Simonart, Brussels H.P. Soyer, Brisbane L. Thomas, Lyon R.M. Trueb, Zürich T.J. Yoon, Jinju Ch.C. Zouboulis, Dessau International Advisory Board