Medallion-like dermal dendrocyte hamartoma: a case misdiagnosed as neurofibroma

Medallion-like dermal dendrocyte hamartoma is a rare congenital lesion, comprised of a benign dermal proliferation of fusiform cells that stain positive for CD34, often positive for factor XIIIa, and negative for S100. It has a highly characteristic clinical presentation consisting of a well-circumscribed atrophic and wrinkled patch located on the upper trunk or neck that remains stable with time. We report a case of an 11-year-old boy with a typical medallion-like dermal dendrocyte hamartoma on the nape of the neck that was previously misdiagnosed as neurofibroma on the basis of initial histological examination that was later reevaluated due to lack of clinical correlation. Three previously-reported cases of medallion-like dermal dendrocyte hamartoma also have had a previous histological misdiagnosis of probable neurofibroma; other reported cases have been misdiagnosed as congenital atrophic dermatofibrosarcoma protuberans. Clinical correlation and immunostaining are particularly important for the recognition of this rare benign lesion.     

Medallion-like dermal dendrocyte hamartoma: a new clinically and histopathologically distinct lesion

Dermal dendrocyte hamartomas are extremely rare; only two examples have been described with clinical features different from our cases and with incomplete immunohistochemical characterization. We report three female patients presenting a medallion-shaped, well-defined, slightly atrophic and asymptomatic congenital lesion. All 3 patients showed a fusiform-cell proliferation. Immunohistochemistry was positive for CD34, factor XIIIa, and fascin. Electron microscopy showed typical features of dermal dendrocytes. We believe that the lesions described represent a new, clinically and histopathologically distinct lesion originating in dermal dendrocytes. We propose to name it medallion-like dermal dendrocyte hamartoma.     

Hypocellular medallion-like dermal dendrocyte hamartoma (plaque-like CD34-positive dermal fibroma)

Medallion-like dermal dendrocyte hamartoma (MLDDH) is a recently described congenital dermal neoplasm. Only 11 cases have been reported in the English literature and therefore its clinical and pathological manifestations are not completely defined. We report the case of a 20-year-old male presenting with a round, erythematous, atrophic plaque on the midline of the anterior aspect of the neck. The lesion was asymptomatic and was stable since birth. A skin biopsy was performed. Histological examination showed a band like hypocellular fibrotic area in the superficial reticular dermis, which did not spread to subcutaneous tissue. The cells were CD34-positive and S100 and CD56-negative. Elastic fibers were present. Altogether the morphological and immunostaining features were neither suggestive of dermatofibrosarcoma protuberans nor neurofibroma. Thus, the pathological findings were consistent with MLDDH. Clinical differential diagnosis includes anetoderma, aplasia cutis, or atrophic DFSP. Histological differential was made with atrophic scar and striae distensae. Although the histological findings were not identical to those described recently as characteristic, the clinical features were suggestive enough to make the diagnosis of MLDDH. Therefore in our experience, the MLDDH spectrum might include lesions with variable cellular density, which can show similar clinical manifestations.     

Hypocellular medallion‐like dermal dendrocyte hamartoma on the abdomen of a 25 year old male

Medallion‐like dermal dendrocyte hamartoma is a rare congenital lesion that is more commonly seen in females. It often presents at birth on the neck or upper trunk as a well‐circumscribed, atrophic patch with wrinkling of the overlying skin. Clinically, the differential diagnosis includes atrophoderma, anetoderma, and congenital atrophic dermatofibrosarcoma protuberans. Histologic findings show epidermal atrophy and dermal spindle cell proliferation that is CD34 positive, along with Factor XIIIa in the original reports. Due to this CD34 positivity, another name for the lesion is plaque‐like CD34+ dermal fibroma. We present a unique patient case as he is male and the lesion is located on his abdomen. Further reports and studies need to be done for thorough understanding of this neoplasm.     

Medallion‐like dermal dendrocyte hamartoma: A rare congenital CD34‐positive dermal lesion clinically and pathologically overlapping with fibroblastic connective tissue nevus

Both medallion‐like dermal dendrocyte hamartoma and fibroblastic connective tissue nevus are rare benign dermal lesions composed of CD34‐positive spindle cells. Although regarded as different diseases, it is sometimes difficult to distinguish between them due to their clinical and pathological similarities. We present a case of medallion‐like dermal dendrocyte hamartoma that could also be diagnosed as fibroblastic connective tissue nevus and propose the possibility of overlap in these diseases.     

Dermatofibrosarcoma protuberans: report of a case with a variant ring chromosome and metastases following pregnancy

Background: The most frequent molecular abnormality observed in dermatofibrosarcoma protuberans (DFSP) is the formation of a supernumerary ring chromosome or translocation resulting in fusion of the gene encoding the α‐chain of type 1 collagen, COL1A1 from 17q22, to the platelet‐derived growth factor β‐chain, PDGFB gene from 22q13. Rare cases documenting variant ring or marker chromosomes involving regions other than 17q22 and 22q13 have been reported. Further analysis in three of these cases demonstrated the presence of the COL1A1 and PDGFB genes. Methods: We report a further case of DFSP with a rare variant ring chromosome. The tumor appeared to undergo accelerated growth during pregnancy, then metastasized following pregnancy. We describe the clinical, histological, immunohistochemical, and cytogenetic features. Results: The metastatic tumor showed a variant r(17;?) chromosome. A locus‐specific probe was required to demonstrate presence of the PDGFB gene within the ring, indicating cryptic molecular rearrangement between chromosomes 17 and 22, and recombination with an unknown chromosome. Conclusions: Cryptic rearrangement of chromosomes 17 and 22 should be suspected in variant ring chromosomes and translocations. Pregnancy may contribute to accelerated growth of DFSP, and delay in surgical resection should be avoided.     

Vascular congenital dermatofibrosarcoma protuberans: a new histological variant of dermatofibrosarcoma protuberans

We describe a case of congenital dermatofibrosarcoma protuberans (DFSP) that masqueraded as a vascular tumor both clinically and histologically. Based on the infiltrative growth pattern, presence of capillary-sized vessels, and spindle cell areas with slit-like vascular spaces and numerous thin-walled vessels at the periphery of the tumor, a kaposiform hemangioendothelioma was initially diagnosed. Strong diffuse CD34 positivity and the extension into the subcutaneous fat with a sieve-like effect prompted the fluorescence in situ hybridization analysis, which demonstrated a reciprocal t(17;22) translocation. According to our knowledge, this is the first report of a vascular histological variant of DFSP. This unique variant represents a potential pitfall for dermatopathologists and underlines the importance of cytogenetic diagnostics in unusual cases of DFSP.     

Congenital Myxoid and Pigmented Dermatofibrosarcoma Protuberans: A Case Report

Dermatofibrosarcoma protuberans (DFSP) is a low‐grade, mesenchymal, spindle cell tumor. In addition to the classical form characterized by a storiform pattern of tumor cells, pigmented (Bednar's tumor) and myxoid variants can be observed. Classical DFSP and Bednar's tumor are easily diagnosed. The myxoid variant represents a diagnostic challenge. Pigmented and myxoid variants are rare and thus far have never been reported in association in congenital DFSP. We came across a unique DFSP that was, at the same time, congenital, pigmented, and myxoid. The tumor was surgically excised with broad free margins and no recurrence. The differential diagnosis with other entities such as giant cell fibroblastoma, CD34‐positive plaque‐like dermal fibroma, superficial plaque‐like CD34 DFSP, and neurocristic hamartoma is discussed. The recognition of this hybrid variant of congenital DFSP is important to avoid under‐ or overtreatment.     

Hypocellular Plaque‐Like CD34‐Positive Dermal Fibroma (Medallion‐Like Dermal Dendrocyte Hamartoma) Presenting as a Skin‐Colored Dermal Nodule

Plaque‐like CD34‐positive dermal fibromas, also known as medallion‐like dermal dendrocyte hamartomas (MDDHs), are a recently recognized group of congenital and acquired spindle cell neoplasms that may appear histologically similar to dermatofibrosarcoma protuberans. Recognizing the clinical heterogeneity of this neoplasm and the subtle pathologic differences are crucial to making the correct diagnosis and avoiding the aggressive surgical intervention required to treat a dermatofibrosarcoma protuberans. We present the case of a 9‐year‐old girl with an acquired variant of a plaque‐like CD34‐positive dermal fibroma without clinical epidermal change. Our case expands the clinical spectrum to include an acquired variant of a plaque‐like CD34‐positive dermal fibroma without clinical epidermal change. Examination of more cases is needed to determine whether all clinical variants are truly subtypes of the same neoplasm or represent distinct CD34‐positive spindle cell proliferations.     

Medallion-like dermal dendrocyte hamartoma

Abstract:  Medallion-like dermal dendrocyte hamartomas are rare congenital cutaneous lesions, with only three occurrences reported in the English language literature. They present at birth as asymptomatic circular, oval, or triangular well-circumscribed, atrophic patches. Typically, they have an erythematous or yellow-brown hue and a characteristic pliable, wrinkled surface; subtle telangiectases may also be appreciated. They may be misdiagnosed as atrophoderma, cutis aplasia, or anetoderma. All reported patients have been female. Characteristic histologic findings include epidermal atrophy and the presence of a CD34-positive spindle cell proliferation in the dermis. This spindle cell proliferation represents a population of dermal dendrocytes, which are bone marrow-derived cells that are believed to function as antigen-presenting cells that contribute to the function of the skin immune system. Little is known about the pathophysiology of medallion-like dermal dendrocyte hamartomas. We present a patient with this entity and review similar presentations reported in the literature.     

Dermatofibrosarcoma Protuberans in Children: an Update on the Diagnosis and Treatment

Abstract: Dermatofibrosarcoma protuberans (DFSP) is a fibrohistiocytic tumor of low grade malignant potential. Although rare, pediatric cases pose a particular challenge in diagnosis and management. In children, the clinical appearance may be heterogeneous and a high index of suspicion is necessary to avoid delays in diagnosis which can lead to further morbidity. Histologic examination, often with the use of appropriate immunostains, is necessary for diagnosis. Advances in the understanding of the molecular genetics of DFSP have led to further diagnostic and therapeutic modalities. DFSP is thought to result from a translocation between platelet‐derived growth factor beta (PDGFB, 22q13.1) and type 1 collagen (COL1A1, 17q21～22) leading to a fusion protein (PDGFB) which stimulates the PDGF receptor. Detection of this translocation in tissue via PCR or fluorescence in situ hybridization (FISH) can be helpful in difficult cases. While surgery with wide local excision or Mohs micrographic surgery is the mainstay of treatment, the use of targeted therapy with imatanib mesylate shows promise in large or unresectable tumors. Knowledge of the clinical features, histology, genetics, and treatment options is important for successful management of these tumors.     

Analysis of the COL1A1-PDGFB fusion gene in a case of dermatofibrosarcoma protuberans with a fibrosarcoma component

Dermatofibrosarcoma protuberans (DFSP) is an infrequent tumor of intermediate malignancy, with little tendency to develop metastases but with a high rate of local recurrence. Cytogenetically, DFSP is characterized by a reciprocal translocation, t(17;22)(q22;q13), which is a conditioning factor in the fusion of the collagen type I alpha I gene (COL1A1) in chromosome 17q with the platelet-derived growth factor beta chain gene (PDGFB) in chromosome 22q. The fusion of these genes is variable, involving one of the 51 exons of the COL1A1 gene and exon 2 of the PDGFB gene. We present the case of a 37-year-old woman with a tumor on the arm whose histology showed a neoplastic infiltration of the subcutaneous cellular tissue made up of fusiform cells with an elongated nucleus in a storiform pattern and other more pleomorphic cells in a herringbone pattern, compatible with DFSP with a fibrosarcoma component. The molecular biology study with RT-PCR analysis of paraffin-embedded material and later sequencing showed a new fusion of exon 19 of the COL1A1 gene and exon 2 of PDGFB, supporting a diagnosis of DFSP. A study of the COL1A1-PDGFB fusion products is useful in cases where histology and immunohistochemistry are insufficient for the differential diagnosis of DFSP versus other sarcomas. It also justifies the use of new avenues of treatment with tyrosine kinase inhibitors.     

Treatment of advanced dermatofibrosarcoma protuberans with imatinib mesylate with or without surgical resection

Background Dermatofibrosarcoma protuberans (DFSP) is a rare soft tissue sarcoma of the skin characterized by the presence of specific COL1A1–PDGFB fusion protein, which appears as a consequence of the t(17;22) (q22;q13) translocation. Objective The aim of the study was to perform an analysis of patients with advanced DFSP treated with imatinib, with or without surgery, in clinical practice outside trials. Patients and Methods We analysed the data of 15 patients (6 male, 9 female; median age 56 years) with locally advanced/initially inoperable and/or metastatic DFSP treated with imatinib 400–800 mg daily between 12/2004 and 06/2009. All diagnoses were ascertained cytogenetically (fluorescent in situ hybridization). Median follow‐up time was 16 months (range: 4–81). Results Metastases were present in six cases (two lungs, two soft tissue, two lymph nodes). Fibrosarcomatous transformation (FS‐DFSP) was confirmed in seven patients (47%). A 2‐year progression‐free survival (PFS) rate was 60%, and a 2‐year overall survival (OS) rate was 78% (median time for PFS/OS was not reached). The best overall responses were: 10 partial responses (67%, including 5 FS‐DFSP – 1 progressed during the follow‐up), 2 stable diseases (13%) and 3 progressive diseases (20%). Seven patients (47%) underwent resection of residual disease and remained free of disease. Conclusions We have confirmed the profound anti‐tumour effect of imatinib in DFSP harbouring t(17;22) with long‐term responses. Imatinib therapy may in some cases lead to tumour resectability of lesser disfiguration.     

Dermatofibrosarcoma protuberans – An Update

Dermatofibrosarcoma protuberans (DFSP) is a rare fibroblastic skin tumor of intermediate malignancy. Its pathogenesis has not yet been fully clarified. Recent basic genetic research has shown chromosomal translocations, generally termed “ring chromosomes”, in DFSP. These arise from a fusion of chromosome regions 17q22 and 22q13, the gene loci which code the alpha chain of type I collagen. The diagnosis is made histologically. Differentiation from atypical dermatofibroma and dermatomyofibroma, as well as from malignant fibrous histiocytoma, whose prognosis is usually much less favorable, can be improved by immunostaining for CD 34 and Factor XIIIa. The extent of the tumors can be estimated by CT and more precisely with MRI. All these techniques fail to detect the fine tumor fascicles extending into the adjacent connective tissue and fat. Surgery is the therapy of choice for DFSP. The locally infiltrative growth pattern features clinically inapparent extensions which often extend for long distances in a horizontal direction. These tumor extensions are best detected by uninterrupted histological check of all margins, including the base (3‐D‐histology), with paraffin sections. Re‐excision of tumor‐positive areas until tumor‐free margins are obtained (“histographic surgery”) insures a high cure rate (97 %) while preserving normal tissue.     

A unique biphasic variant of cutaneous fibrous histiocytoma with a storiform pattern and intralesional pigmented melanocytes: "storiform melano-fibrous histiocytoma"

Dermatofibromas (cutaneous fibrous histiocytomas) are common cutaneous neoplasms of mesenchymal origin. They are often associated with epidermal hyperplasia and increased basal layer pigmentation. There have been reports of a spectrum of melanocytic lesions associated with dermatofibromas ranging from junctional nevi to malignant melanomas, some of which may be coincidentally associated. We report a case of a long-standing storiform fibrohistiocytic lesion devoid of cytological atypia, lacking extension into subcutaneous fat, not demonstrating the t(17;22) DFSP translocation yet showing diffuse and strong CD34 immunoreactivity and containing pigmented spindle shaped melanocytic cells admixed with the fibrohistiocytic component. This case raises a nosological debate given the histological, immunophenotypic and cytogenetic findings.     

Stromelysin-3 expression in the differential diagnosis of dermatofibroma and dermatofibrosarcoma protuberans: comparison with factor XIIIa and CD34

BACKGROUND: The distinction between dermatofibroma (DF) and dermatofibrosarcoma protuberans (DFSP) is a well-known challenge for dermatopathologists. Immunohistochemical stains have been used to augment routine histological examination to aid in differentiating DF from DFSP. Stromelysin-3 (ST3) is a member of the matrix metalloproteinase (MMP) family, MMP-11, which is expressed in the skin during wound healing and in the stroma of basal cell carcinoma. Recent studies demonstrated that DFs expressed ST3, whereas DFSPs were only rarely ST3 positive. OBJECTIVES: To assess the expression of ST3 in DF and DFSP and to ascertain whether ST3 is superior to factor XIIIa or CD34 in differentiating DF from DFSP, by comparison with factor XIIIa and CD34 expression. METHODS: Immunohistochemical staining was performed on 23 cases of DF and 17 cases of DFSP, using antibodies to ST3, factor XIIIa and CD34. RESULTS: ST3 was expressed in all cases of DF (23 of 23) but only one case showed weakly positive staining in DFSP (one of 17). The mean +/- SD ST3 immunohistochemistry (IHC) score in DF was 4.52 +/- 0.67. The sensitivity of ST3 was 100% and the specificity was 94%. Factor XIIIa was expressed in all cases of DF (23 of 23) and in five of the 17 DFSPs. The mean +/- SD factor XIIIa IHC score in the DFs was 4.43 +/- 0.73. The sensitivity of factor XIIIa was 100% and the specificity was 71%. CD34 was expressed in four of the 23 DFs and 16 of the 17 DFSPs. The mean +/- SD CD34 IHC score in the DFSPs was 4.41 +/- 1.37. The sensitivity of CD34 was 94% and the specificity was 83%. CONCLUSIONS: Immunohistochemical staining with a commercial anti-ST3 antibody can be successfully carried out in routine dermatopathology. We confirmed that ST3 is a positive marker for DF and that ST3 staining might be more reliable than factor XIIIa staining in differential diagnosis of DF and DFSP. As the present study showed that ST3 was not absolutely negative in all cases of DFSP, the combination with CD34 immunostaining could make the distinction more reliable.     

A congenital smooth muscle hamartoma masquerading as a reticulate vascular naevus

Smooth muscle hamartoma (SMH) is a benign congenital or acquired hamartomatous lesion comprising a dermal proliferation of smooth muscle bundles. We report a case of congenital SMH with an unusual clinical appearance. A 3‐year‐old girl presented with an asymptomatic atrophic linear lesion on the posterior surface of her right thigh, which had been present since birth. The striking resemblance to a vascular lesion initially led to the erroneous clinical diagnosis of atrophic reticulate vascular naevus. However, a skin biopsy showed typical features of SMH. To our knowledge, SMH with linear configuration has only been described in two previous cases, and there are no previous reports of SMH with such a marked resemblance to a vascular lesion.