Desmoplastic Nevus Research Articles

Next-generation Sequencing as a Potential Diagnostic Adjunct in Distinguishing Between Desmoplastic Melanocytic Neoplasms.

Desmoplastic melanomas (DMs) are often challenging to diagnose and ancillary tests, such as immunohistochemistry, have limitations. One challenge is distinguishing DM from benign desmoplastic melanocytic neoplasms. In this study, we explored the utility of next-generation sequencing data in the diagnosis of DMs versus desmoplastic Spitz nevi (DSN) and desmoplastic nevi (DN). We sequenced 47 cases and retrieved 12 additional previously sequenced clinical cases from our dermatopathology database. The 59 total cases were comprised of 21 DMs, 25 DSN, and 13 DN. The DMs had the highest tumor mutation burden at 22 mutations/megabase (m/Mb) versus the DSN (6m/Mb) and DN (8m/Mb). Truncating mutations in NF1 resulting in a loss-of-function were exclusive to the DM cohort, identified in 8/21 (38%) cases. Importantly, missense mutations in NF1 were nonspecific and seen with similar frequency in the different cohorts. Other mutations exclusive to the DMs included truncating mutations in TP53 , CDKN2A , and ARID2 . Among the DSN, 17/25 (68%) had an HRAS mutation or receptor tyrosine kinase fusion consistent with other Spitz tumors. Two cases in the DN cohort had missense mutations in BRAF without additional progression mutations and 2 other cases had mutations in GNAQ , supporting a diagnosis of a sclerosing blue nevus. The remainder of the DN had nonspecific mutations in various signaling pathways with few progression mutations. Overall, our study provides preliminary data that next-generation sequencing data may have the potential to serve as an ancillary diagnostic tool to help differentiate malignant and benign desmoplastic melanocytic neoplasms.

A Case of Blue Nevus Mimicking Malignant Melanoma Within a Keloid Scar

Blue nevus is a type of melanocytic nevus which clinically presents itself as blue/gray plaque or nodule. It most commonly develops upon distal extremities especially dorsal hands and feet, trunk and scalp. Histopathologically, heavy melanocyte aggregations in the deep dermis result in blue nevus formation. Different types of blue nevus include common blue nevus, cellular blue nevus, plaque-type blue nevus, combined blue nevus, desmoplastic blue nevus and subungal blue nevus. Although clinical findings may be sufficient to diagnose blue nevus, dermoscopy could be used as a helpful tool to aid in reaching the correct diagnosis. Dermoscopy usually shows diffuse blue-gray structureless area but since atypical clinical and dermoscopical features may be observed, histopathological diagnosis is the definitive step to differentiate blue nevus from its mimickers such as malignant melanoma. We want to present an interesting case of blue nevus mimicking malignant melanoma developing in a scar.

Gene expression signature as an ancillary method in the diagnosis of desmoplastic melanoma

Desmoplastic melanoma (DM) is a rare fibrosing variant of melanoma that can be difficult to diagnose. One of the diagnostic challenges is its distinction from a melanocytic nevus with desmoplasia. Here we investigate the use of a 23-gene signature, which has previously been shown to distinguish benign from malignant melanocytic neoplasms. We assessed 50 cases with a differential diagnostic consideration of DM that underwent gene expression testing. Hematoxylin and eosin-stained sections were reviewed, and the final cohort included 20 DMs, 5 nondesmoplastic melanomas, and 27 desmoplastic melanocytic nevi. Of the 20 DMs, the gene expression score was positive ("likely malignant") in 15 tumors, indeterminate in 1, and negative ("likely benign") in 4. None of the desmoplastic melanocytic nevi were positive. The gene expression score was negative in 24 of the melanocytic nevi and indeterminate in the remaining 3. Nine DMs were also analyzed cytogenetically by single-nucleotide polymorphism (SNP) array. The SNP array revealed chromosomal copy number aberrations consistent with melanoma in 7 DMs and failed to show any aberrations in 2. The results of SNP array analysis and gene expression testing were discordant in 4 cases. Our results document limitations in the sensitivity of both the gene expression signature and SNP array for the detection of DM. Nonetheless, our findings suggest a potential role of the gene expression signature as ancillary supportive evidence for the distinction of DM from desmoplastic nevus because positive scores were only seen in melanomas.

Clinicopathologic analysis of four cases of desmoplastic melanocytic nevus

Objective To investigate pathological characteristics and differential diagnosis of desmoplastic melanocytic nevus. Methods Four cases of desmoplastic melanocytic nevus were analyzed based on the clinical manifestations and histological, immunohistochemical and fluorescence in situ hybridization (FISH) features. Results Of the 4 cases, 2 were male and 2 were female. Their age ranged from 19 to 30 years with the average age being 26.5 years. The skin lesions were located on the extremities in 3 cases, on the vulva in 1 case. Histologically, the lesions were bilaterally symmetrical intradermal nevus. Nevus cells appeared epithelioid and/or fusiform, some were clustered or scattered in the proliferative fibrous tissue. None of lymphocyte aggregation, necrosis or ulceration was observed. Immunohistochemical examination showed positive staining for S100 and Melan A in 3 cases, positive staining for P16 in 2 cases, Ki-67-labeling index less than 5% in all the 4 cases, and negative staining for factor XIII (FXIII) and CD34 in 2 cases. FISH assay showed no copy-number variations in gene loci 6p25 (RREB1) , 6q23 (MYB) , 6p11.1-q11.1 (Cep6) and 11q13 (CCND1) in desmoplastic melanocytic nevus. Conclusion Desmoplastic melanocytic nevus is a kind of histologically unique, benign melanocytic nevus, and immunohistochemical staining for Ki-67, S-100, Melan A and FⅩⅢand FISH assay on melanoma can be helpful for the differential diagnosis between cutaneous fibrous histiocytoma and melanoma. Key words: Nevus, pigmented; Pathologic processes; Skin manifestations; Immunohistochemistry; Desmoplastic melanocytic nevi; FISH

Desmoplastic nevus of chronically sun-damaged skin: an entity to be distinguished from desmoplastic melanoma.

Desmoplastic (sclerotic) nevus (DSN) can often be difficult to differentiate from desmoplastic melanoma (DM). This can be especially difficult when DSNs occur in a background of heavy solar elastosis. We have observed numerous examples of DSNs occurring in chronically sun-damaged (CSD) skin. In a subset of these cases, we have observed notable pleomorphism and nuclear atypia raising concern for the possibility of DM. In this study, we evaluated the clinical, histopathologic, and immunohistochemical findings in 23 cases of DSN occurring in CSD skin and compared them with 10 cases of DM. DSN on CSD skin is seen in adults (mean, 53.2 years) with a female predominance (70%) and upper (57%) and lower (17%) extremity anatomic locations. Most DSNs present as small flesh-colored macules or papules. Typical histologic features include symmetry, limited junctional growth, presence of a lentiginous component often with focal and limited pagetoid spread (extension across only a few rete ridges), and lack of deep extension. DSN and DM had a statistically significant difference in immunohistochemical staining for Melan-A and p75. Melan-A was positive in 18 of 20 DSNs and only 2 out of 10 DMs, whereas p75 was positive in all DMs (10/10) and was weakly positive in 11 of 20 DSN cases. We believe that our study offers some useful clinical, histologic, and immunohistochemical clues to help differentiate DSNs on CSD skin from DMs.

Desmoplastic Nevus: An entity Distinct From Spitz Nevus and Blue Nevus

Desmoplastic (sclerotic) nevus is an infrequently reported poorly characterized benign melanocytic proliferation, with only 4 case series published to date. To better define this nevus, we examined the clinical and histologic features of 25 lesions. Desmoplastic nevus is seen in both children and adults and can be located on the face, trunk, or extremities. There is a female predominance. Clinically, it can resemble intradermal nevus, atypical nevus, melanoma, and pigmented basal cell carcinoma. These are generally small, symmetric, and well-circumscribed lesions, averaging 3.5 mm in diameter. The most distinctive features include predominantly compound growth, a zonal configuration with greater cellularity in the superficial portion of the lesion, and a mixture of melanocytic phenotypes including type A, B, and C nevus cells, ovoid and dendritic melanocytes, and Spitzoid melanocytes. A distinctive eosinophilic stroma which either resembles that of a dermatofibroma or neurofibroma is always present. Variable amounts of melanin pigment are found in both tumor cells and macrophages, but this is not a prominent feature. Mitotic activity is exceedingly rare (1 case), and pleomorphism is minimal. These lesions are distinct from typical compound nevus, Spitz nevus, epithelioid blue nevus, and desmoplastic melanoma, to which they are often compared. Strict application of these histologic features allows definitive diagnosis of desmoplastic nevus as a distinct form of a benign melanocytic nevus.

The role of lymphatic mapping and sentinel node biopsy in the management of atypical and anomalous melanocytic lesions

Atypical and anomalous melanocytic lesions are tumors that cannot be determined by microscopy to be certainly benign or fully malignant. The malignant potential of these borderline lesions is unknown and logical determination of best therapy is challenging, in particular whether lymphatic mapping and sentinel node biopsy have a place in their management. Lesions that fall into this category include atypical Spitzoid lesions, atypical cellular blue nevi, combined nevi, deep penetrating nevi, ancient nevi, desmoplastic nevi, balloon cell nevi and proliferation nodules of congenital nevi. We report our experience managing patients with these problematic tumors and discuss our approaches to determining the true location of lesional cells in sentinel nodes.

Desmoplastic Nevus: Clinicopathologic Keynotes

We describe 3 cases of desmoplastic nevus with special emphasis on some repetitive dermoscopic and histopathologic features, which-if confirmed on larger series-could allow to identify desmoplastic nevus as a specific clinicopathologic entity within the spectrum of acquired melanocytic nevi.

Melanocytic nevi simulant of melanoma with medicolegal relevance

A group of melanocytic benign nevi are prone to be misdiagnosed as nodular or superficial spreading melanoma. This review illustrates the most frequent forms of these nevi in direct comparison with their malignant morphologic counterparts. The nevi are: hyper-cellular form of common nevus to be distinguished from nevoid melanoma, Spitz nevus (vs spitzoid melanoma), Reed nevus (vs melanoma with features of Reed nevus), cellular atypical blue nevus (vs melanoma on blue nevus), acral nevus (vs acral melanoma), Clark dysplastic nevus (vs superficial spreading melanoma), desmoplastic nevi (vs desmoplastic melanoma), benign proliferative nodules in congenital nevi (vs melanoma on congenital nevi), epithelioid blue nevus (vs animal type melanoma) and regressed nevus (vs regressed melanoma). For each single 'pair' of morphological look-alikes, a specific set of morphological, immunohistochemical and genetic criteria is provided.

Displacement of dermal solar elastosis in malignant melanoma

Ultraviolet radiation (UVR) is a major environmental causal factor for skin malignancy. In this study, we investigated the morphology of the solar elastosis (SE) band in benign and malignant melanocytic lesions. We measured the SE band in perilesional and lesional skin of 13 melanomas (9 invasive and 4 in situ) and 11 melanocytic nevi (5 usual intradermal nevi, 4 blue nevi and 2 desmoplastic nevi) occurring in sun-exposed areas. The melanoma and nevus groups had similar age range, gender ratio and anatomic distribution. The mean SE thickness was 0.35 mm in melanomas and 0.29 mm in nevi (p = 0.56), indicating similar UVR exposure. There was a mean downward SE displacement (SED) of 0.43 mm in melanomas and essentially no displacement (-0.02 mm) in nevi (p < 0.005). Tumor cells and inflammatory host response were responsible for SED in melanoma. SED may help in the differential diagnosis of melanocytic lesions in sun-exposed areas. In melanoma, the new lesion depresses the pre-existing SE band. Conversely, the long-standing nevus co-exists with the SE band without significant displacement. Evaluation of the SE band may help to differentiate melanoma with chronic sun-induced damage as they have a distinct set of molecular alterations.

Expression of Melan-A and Ki-67 in Desmoplastic Melanoma and Desmoplastic Nevi

Desmoplastic melanoma (DMM) is an uncommon melanoma variant with a distinct morphology, including a prominent spindle cell component with fibrosis, as well as a distinct immunohistochemical profile. Histologically, the spindle cell component of DMM can be confused with sclerotic/desmoplastic nevi, nonpigmented blue nevi, scar, and neural tumors. The histological distinction between sclerotic/desmoplastic/blue nevi and DMM using standard light microscopic techniques can be exceedingly subtle. Therefore, we investigated whether immunohistochemical staining for Melan-A and Ki-67 expression can be used to discriminate these lesions, distinguishing between epithelioid and spindle cell compartments of the lesions. Fifty cases of DMM and 13 cases of sclerotic/desmoplastic/blue nevi were identified. Standard immunohistochemical techniques were used with antibodies towards HMB-45, Melan-A (A103), and Ki-67; 43 of 50 DMM cases were available for staining with Melan-A, 42 of 50 for HMB-45, and 31 of 50 cases were stained with Ki-67. All 13 nevi were stained for Melan-A and 8 for Ki-67. Immunoreactivity to Ki-67 antibody was scored as 0 to 5%, 6 to 10%, 11 to 30%, or greater than 30% positive tumor cells. Only 3 of 43 and 3 of 42 of spindle cell compartments of DMMs were positive for Melan-A and HMB-45, respectively. Focal staining of epithelioid cells in the junctional component or superficial dermis was observed in 33% (14/43). In contrast, 100% of the 13 nevi were strongly positive for Melan-A (P < 0.001). Seventeen melanomas (55%) were 0 to 5% positive for Ki-67, five (16%) fell into the 6 to 10% category, three (10%) were between 11 and 30%, and six (19%) were at least focally greater than 30% positive. All 8 nevi (100%) had less than 5% positive cells for Ki-67 (P = 0.02), with only 2 cases having more than 2% positive cells. The sclerotic/desmoplastic and hypopigmented blue nevi were uniformly positive for Melan-A, while the vast majority of DMM were negative in their spindle cell compartments. Melan-A is very useful in distinguishing between DMM and sclerotic nevi. Ki-67 appears to be an inconsistent marker for DMM. However, a high labeling index (over 5%) may be used as a clue in diagnosing DMM.

The anti-MAGE antibody B57 as a diagnostic marker in melanocytic lesions.

The differentiation of melanoma from certain benign melanocytic lesions on histologic grounds alone may sometimes be difficult. The anti-MAGE antibody 57B was suggested to be a useful adjunct in differentiating melanoma from nevi. Our aim was to study MAGE immunoreactivity with B57 in benign melanocytic lesions that have not been investigated to this end so far. One hundred six benign melanocytic lesions were stained with the monoclonal antibody 57B. They included deep-penetrating nevus (n = 6), desmoplastic nevus (n = 9), halo nevus (n = 10), persistent melanocytic nevus (n = 12), common blue nevus (n = 17), cellular blue nevus (n = 8), cellular blue nevus with microalveolar pattern (n = 3), desmoplastic cellular blue nevus (n = 6), epithelioid blue nevus (n = 2), sclerotic blue nevus (n = 3), and clonal nevus (n = 30). Fifty-two lesions (49%) demonstrated various patterns of MAGE immunoreactivity, with clonal nevi and deep-penetrating nevi showing the most consistent staining. In conclusion, MAGE immunoreactivity detected by the monoclonal antibody 57B in formalin-fixed, paraffin-embedded tissue can be observed in benign melanocytic lesions, and therefore this antibody cannot be used in the differential diagnosis between melanoma and nevi.