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Desmoplastic melanoma (DM) is a less common form of cutaneous melanoma that has been described for decades; however, controversy remains regarding the management and use of sentinel lymph node biopsy (SLNB). The purpose of this study is to identify whether SLNB is indicated in all cases of DM, including the pure subtype. A systematic review was conducted using PubMed (with access to MEDLINE) along with the Cochrane Central Register of Controlled Trials from 2001 to 2019. Case series and case-control studies were included. Eighteen studies were included for a total population of 3,914 patients. SLNB was performed in 2229 patients. The percentage of positive SLNB results was 8.5%. However, patients with pure DM (>90% desmoplastic component) were found to have a significantly lower rate of occult metastatic node positivity when compared with that of mixed DM (4.9% and 14.8%, respectively). Our findings underscore the importance of the pathologist reporting percentage of desmoplastic component in melanoma. SLNB should be strongly considered for patients with mixed DM. However, the low rate of occult metastatic node positivity in pure DM is beneath the threshold for using SLNB as a staging procedure. Previous studies have suggested that desmoplastic melanoma is less likely to metastasize to regional lymph nodes when compared with conventional melanoma. This review suggests that it is imperative to distinguish the histologic subtype of desmoplastic melanoma to determine if staging procedure is indicated. [ABSTRACT FROM AUTHOR]

There are multiple, genetically distinct pathways that give rise to melanoma. Melanomas on sun-damaged skin (MSDS), including lentigo maligna and desmoplastic melanoma, have distinct genetic profiles and are uniquely linked to chronic ultraviolet exposure. In this article, we discuss the etiologies of lentigo maligna and desmoplastic melanoma, emerging diagnostic adjuncts that might be helpful for accurately identifying these lesions, and the clinical relevance of their frequent co-occurrence. We present unique and overlapping features of these entities and discuss challenges in MSDS management, including margin assessment, excision, and the potential role of nonsurgical therapy. Last, we address the role of immunotherapy in invasive disease. Understanding MSDS as distinct from melanoma arising on intermittently sun-exposed or sun-protected skin will ultimately help optimize patient outcomes. [ABSTRACT FROM AUTHOR]

Background: The prognostic role of programmed death ligand 1 (PDL1), CD8, and forkhead box p3 (FoxP3) expression in desmoplastic melanomas is unclear.Methods: We correlated PDL1, p53, and Ki-67 expression with CD8+ and FoxP3+ immune infiltrates with clinicopathologic variables and patient outcomes in a series of 66 desmoplastic melanomas.Results: Tumoral PDL1 expression (≥25%), which was seen in 21% of patients (14 of 66), significantly correlated with mixed histology, tumor thickness, mitoses, recurrence, and metastasis. According to linear regression analysis, tumoral PDL1 expression correlated with thickness (P = .0041); p53 expression (P = .019); Ki-67 proliferation index (P = .0018); and tumoral CD8 (P = .0084), stromal CD8 (P < .0001), and FoxP3 (P < .0001) T-cell counts. According to univariate analyses, PDL1 expression of 25% or higher correlated with shorter progression-free survival (P < .0001) and melanoma-specific survival (P = .034). According to multivariate analyses, PDL1 expression of 25% or more (P = .026) and mixed histology (P = .039) independently predicted shorter progression-free survival, and presence of lymphovascular invasion predicted shorter overall survival (P = .018).Limitations: Small study size.Conclusion: Tumoral and stromal CD8+ and FoxP3+ lymphocyte counts correlated with tumoral PDL1 expression, which is supportive of an adaptive immune response. PDL1 expression in desmoplastic melanoma was associated with tumor aggressiveness and progression. Although PDL1 expression is typically low in melanoma, its frequency and level of expression in desmoplastic melanoma may identify a subset of melanomas that are likely to respond to immunotherapy. [ABSTRACT FROM AUTHOR]

Background: The prognostic role Ki-67, p53, and p16 immunostains and RET (rearranged during transfection) polymorphism in desmoplastic melanoma has not been evaluated.Objective: We sought to identify potential prognostic markers.Methods: We performed Ki-67, p53, and p16 immunostains on 66 desmoplastic melanomas, and sequenced RET G691 polymorphism and recurrent mutations of 17 cancer genes in 55 and 20 cases, respectively.Results: Recurrence and metastasis were documented in 11 of 66 (17%) and 26 of 66 (39%) patients, respectively. Death was noted in 25 of 55 (45%) patients. Ki-67 expression (≥10%, 43%) correlated with male gender (P = .009), ulceration (P = .002), and Breslow depth (P = .009). p53 Expression (≥50%, 28%) correlated with male gender (P = .002) and head and neck location (P = .0228). Using Kaplan-Meier plots, Ki-67 expression (P = .0425) and mitosis (P = .00295) correlated with overall survival, whereas vascular invasion (P = .0292) correlated with disease progression. There was a significant correlation between Ki-67 and p53 expression (P = .003). RET polymorphism was present in 10 of 46 (22%) cases and inversely correlated with Breslow depth (P = .024).Limitation: Our study is small and lacks power to perform a multivariate analysis.Conclusion: Although Ki-67 expression correlated with overall survival, additional studies are needed to determine whether Ki-67 would be an independent prognostic marker in addition to the current routine histopathologic assessment. [ABSTRACT FROM AUTHOR]

Background Perineural invasion (PNI) in desmoplastic melanoma is associated with increased local recurrence and reduced disease-free survival. The biological mechanisms underlying PNI remain unclear although several lines of evidence implicate neurotrophins and their receptors. Objectives We investigated the expression of p75NGFR and TrkA, and the presence of functional RET polymorphism (RETp) as they relate to PNI in desmoplastic melanoma. Methods In all, 43 cases of desmoplastic melanoma were immunohistochemically evaluated for TrkA and p75NGFR expression and RETp was detected by direct DNA sequencing. Results PNI was present in 67% of cases. On univariate analysis, p75NGFR was associated with PNI (expression detected in 79% of PNI-positive cases compared with 36% of PNI-negative cases, P = .005), increased Breslow depth ( P = .007), and greater Clark level ( P = .01). RETp was noted in 28% of cases but was not significantly associated with PNI ( P = .27) or other histopathologic variables. TrkA expression was absent in all cases. PNI was associated with increased Breslow depth and Clark level ( P = .01 and P = .009, respectively). Controlling for the association between p75NGFR and depth, p75NGFR remained associated with an increased propensity for PNI (odds ratio 4.68, P = .04). Limitations The sample size was limited. Conclusion In desmoplastic melanoma, p75NGFR expression is significantly associated with PNI and a more locally aggressive phenotype. [ABSTRACT FROM AUTHOR]

A 56-year-old woman with neurofibromatosis type 1 (NF1) presented with a left upper eyelid amelanotic nodule with adjacent eyelid margin hyperpigmentation. Physical examination additionally revealed primary acquired melanosis (PAM) on the palpebral conjunctiva of the same eyelid. Full thickness eyelid excision and conjunctival map biopsy identified desmoplastic melanoma of the eyelid in addition to invasive conjunctival melanoma and conjunctival melanoma in situ. Sentinel lymph node biopsy was negative for metastasis. She was treated with surgical excision for the eyelid melanoma and topical mitomycin C for the conjunctival melanoma. We discuss the rare entity of desmoplastic melanoma of the eyelid and its possible association with NF1. [ABSTRACT FROM AUTHOR]

Abstract: Aims: Given the paucity of data regarding nodal involvement in desmoplastic melanoma (DM), we decided to review the incidence of nodal metastasis in our patients with DM to better define guidelines regarding the performance of sentinel lymph node biopsy (SLNB) in this specific melanoma subtype. Methods: Using a prospectively maintained database, we reviewed all patients who underwent treatment for melanoma at the Yale Melanoma Unit in a twelve-year period (1998–2010), during which 3531 cases were treated. We identified 24 patients (0.7%) diagnosed with DM. These patients' records were studied for clinical and histologic parameters and clinical outcomes. Results: Twenty-two patients from the DM group had SLNB, of which four (18%) were diagnosed with micro-metastasis. These four patients were all treated with completion lymphadenectomy and none had additional positive nodes in the remainder of the nodes. Patients were followed after surgery for a median of 25 months (range 2–60 months). Two patients (9%) developed local recurrence, two (9%) in-transit recurrence, and six (27%) showed distant metastases (three patients were pure DM and three patients showed mixed morphology). Patients with mixed DM had a higher rate of nodal metastasis (25%) vs those with pure DM (14%). Conclusions: Other authors have reported that patients diagnosed with pure DM were less likely to have a positive SLN (0–2%) than those patients with the mixed DM subtype (12–16%). Our findings of higher incidence rates of regional lymph node metastases in both the pure and mixed DM subtypes (14% and 25%) compel us to continue to still recommend that SLNB be considered in patients with both subcategories, pure and mixed DM. Level of evidence: Level IV. [Copyright &y& Elsevier]

Desmoplastic melanoma (DM) is a variant of spindle cell melanoma typically found on chronically sun-damaged skin of older individuals. Early diagnosis can be challenging because it is often amelanotic and has a predominantly dermal component. DM can be difficult to diagnose not only clinically but also histologically, and can be mistaken for a variety of benign and malignant nonmelanocytic spindle cell tumors when viewed on prepared histopathology slides. Pathologists have observed that DMs can manifest significant variation with respect to the extent of intratumoral cellularity, fibrosis, and/or perineural invasion. Furthermore, some tumors present with a pure desmoplastic invasive component (>90%) while other tumors display mixed features of DM and nondesmoplastic melanoma. This has led to the separation of DM into 2 histologic subtypes, pure and mixed. With a focus on the distinction between pure and mixed DM, this review will detail what is currently known about the diagnostic features of DM, discuss risk and prognostic factors, and examine the current literature on disease progression and management. [Copyright &y& Elsevier]

Background: Spindle cell melanoma (SCM) including desmoplastic melanoma (DM) is a rare variant of malignant melanoma that may present diagnostic difficulties particularly when staining with S100 is negative, weak, focal, or a combination of these. Conventional melanocytic markers in SCM are usually negative. Objective: We sought to compare the staining of p75 nerve growth factor receptor (NGF-R) and S100 in SCMs. Methods: We evaluated the staining of p75 NGF-R and S100 in 13 cases of SCMs: 3 SCMs without desmoplasia, 5 pure DMs, and 5 combined DMs with a conventional component. Results: Staining with p75 NGF-R was positive in 13 of 13 (100%) cases of SCMs. In 3 cases the intensity of staining and the percentage of cells staining with this marker were greater than those with S100. One case of SCM was negative for S100 but demonstrated strong expression of p75 NGF-R. One case was focally and weakly positive with S100 but expressed strong positive staining with p75 NGF-R. Absence of staining with p75 NGF-R was noted in the conventional round cell component of two of 5 (40%) combined DMs whereas the same areas were strongly positive for human melanoma black (HMB)-45 and Melan-A. In 5 of 5 (100%) cases of combined DMs the desmoplastic component stained positive with p75 NGF-R, demonstrating an inverse relationship with the staining of conventional melanocytic markers. Limitations: Small study size was a limitation. Conclusion: p75 NGF-R exhibits superior staining characteristics and greater sensitivity in identifying SCM and DMs than S100. P75 NGF-R may be a useful diagnostic and ancillary stain in addition to S100. [ABSTRACT FROM AUTHOR]

Summary: Desmoplastic melanoma is a variant of spindle cell melanoma considered at low risk for distant metastases when compared with other forms of melanoma. The emphasis in the differential diagnosis of desmoplastic melanomas has been placed mostly in distinguishing it from scars and other benign spindle cell proliferations. In contrast, recognizing a subset of desmoplastic melanomas with higher metastatic potential has proven more difficult. We studied the expression of N-cadherin in 21 desmoplastic melanomas. The expression of N-cadherin was examined by immunohistochemistry using archive material and a mouse anti–N-cadherin monoclonal antibody previously shown to react in routinely processed paraffin-embedded tissues. Of 21 cases, N-cadherin was strongly positive in 10, only weakly or focally positive in 3, and negative in 8. Seven of 21 patients had distant metastases, and N-cadherin was strongly positive in 6 of those 7 cases. In contrast, only 1 of 11 patients within the group of N-cadherin–negative or weakly positive tumors had distant metastases. Our results show that strong N-cadherin expression in desmoplastic melanoma correlates with distant metastases and potentially more aggressive behavior. In contrast, desmoplastic melanomas with low metastatic potential are mostly negative or only focally positive for N-cadherin. The data suggest that N-cadherin may be a useful marker in recognizing a subset of desmoplastic melanoma with higher metastatic potential. [Copyright &y& Elsevier]

Desmoplastic melanoma (DM) is an uncommon variant of malignant melanoma (MM), histologically characterized by a mainly dermal proliferation of spindled cells within a desmoplastic stroma. Normally, involvement of deeper tissues by DM is the result of direct extension down from the overlying dermis. MM is widely known to harbor a striking potential for morphological and phenotypic variability; among MM morphological variants, pseudoglandular MM is characterized by extensive discohesion within cords and nests of malignant cells and ensuing formation of so-called pseudolumina, thus mimicking adenocarcinoma. We present an exceptional case of DM characterized by intrafascial origin, partly pseudoglandular differentiation, and aberrant experession of cytokeratins in the pseudoglandular component; genetic data from next-generation sequencing supported the final diagnosis of DM, as well as the ontogenetic identity of the pseudoglandular component. Prior to this report, pseudoglandular features had never been described in DM. Additionally, our case is unusual because of the deep origin of the tumor, arising below the subcutaneous fat of the scalp, as well as the aberrant experession of cytokeratins in the pseudoglandular component, thus posing a challenging differential diagnosis with several soft tissue tumors. [ABSTRACT FROM AUTHOR]