The Importance of In Vivo Reflectance Confocal Microscopy in a Case of Desmoplastic Melanoma.

Desmoplastic melanoma accounts for 5% of all cases of melanoma, but its diagnosis can be difficult due to its frequent clinical presentation with amelanotic lesions. Histologically, spindled melanocytes surrounded by a collagenous stroma are observed. Compared with other types of melanoma, the desmoplastic types presents greater local aggression, and is more prone to local recurrence, but has a lower risk of lymph node metastasis. Early detection, accurate staging, and proper surgical management are the main factors associated with higher survival rates in melanoma patients. Reflectance confocal microscopy (RCM) has proven to be a valuable imaging tool in the diagnosis of skin neoplasms, being useful for orientating practitioners towards the diagnosis of melanoma and indicating the necessity of performing a diagnostic biopsy. We present the case of 52-year-old woman, who presented to the dermatology department with an irregular, dark-colored plaque in the right deltoid region. Dermoscopy showed asymmetry with an atypical network and some areas of regression. RCM revealed pagetoid cells in the upper epidermis, cell atypia, non-edged papillae, dermal inflammation, and nucleated cells in the dermis, which are highly suggestive of melanoma. A biopsy was also performed. A histopathology exam confirmed the diagnosis of superficially spreading melanoma with a desmoplastic component, and revealed a Breslow index of 0.9 mm, Clark level IV, an absence of mitoses, angiolymphatic invasion and regression, and complete excision. The CT and PET-CT scans were negative. A biopsy of the axillary sentinel lymph node was conducted, with a negative result obtained, establishing the IB stage of the disease. The patient will remain under follow-up to look for a recurrence or a new primary melanoma.

Case report: Is severe toxicity the price to pay for high sensitivity to checkpoint inhibitors immunotherapy in desmoplastic melanoma?

Background: Desmoplastic melanoma (DM) is a rare subtype of melanoma characterized by high immunogenicity which makes it particularly suitable for immune checkpoint inhibitors (ICIs) treatment. Case presentation: We report the case of a 53-year-old man with metastatic DM successfully treated with the combination of anti-CTLA-4 and anti-PD-1 antibodies, who developed serious immune-related adverse events (irAEs). The primary tumor was characterized by absent PD-L1 expression and no-brisk lymphocytes infiltration. NGS showed absence of BRAF mutation, a high tumor mutational burden, and an UV-induced DNA damage signature. Metastatic lesions regressed rapidly after few cycles of ICIs until complete response, however the patient developed serious irAEs including hypothyroidism, adrenal deficiency, and acute interstitial nephritis which led to the definitive suspension of treatment. Currently, the patient has normal renal functionality and no disease relapse after 26 months from starting immunotherapy, and after 9 months from its definitive suspension. Conclusion: Efficacy and toxicity are two sides of the same coin of high sensitivity to ICIs in DM. For this reason, these patients should be closely monitored during ICIs therapy to promptly identify serious side effects and to correctly manage them.

Desmoplastic Melanoma of the Chest Wall: a Diagnostic Dilemma.

Desmoplastic melanoma is an extremely rare subtype of malignant melanoma comprising only 1% of all the cutaneous melanomas. Being amelanotic and owing to its histopathological features of spindle cells lying in a collagenized stroma, it is often misdiagnosed as a dermatofibroma or scar tissue. The present case study describes a case of desmoplastic melanoma of the chest wall where the final diagnosis could be arrived at only after an extensive immunohistochemical panel to exclude other spindle cell proliferations.

The utility of SOX10 in mixed type desmoplastic melanoma with lymph node metastasis of the spindle cell component: A cautionary tale of inattentional blindness.

Desmoplastic melanoma (DM), a type of spindle cell melanoma separated into pure desmoplastic melanoma (PDM) and mixed desmoplastic melanoma (MDM) subtypes, can be a diagnostic challenge and easily confused for dermal scar, especially PDM. We report a 65-year-old white man who received a left thumb amputation after an initial biopsy for melanoma, an unclassified type with epithelioid morphology. The amputation and sentinel lymph node specimens were significant for residual melanoma with epithelioid morphology, dermal scar, and a slightly expanded "scar-like" capsular area in one of seven lymph nodes, which was diffusely positive for SOX10 on reflex sentinel lymph node immunohistochemical protocol. On re-review of the amputation "scar" like area, a subsequent SOX10 stain confirmed the diagnosis of MDM in this area with epithelioid and spindle cell morphology, significantly upgrading the tumor stage. We share this case to highlight: (i) MDM, although exceptionally uncommon, can result in a pure spindle cell lymph node metastasis, (ii) to encourage increased utilization of SOX10 to assess sentinel lymph node biopsies, especially in the context of melanomas with a spindle cell component, and (iii) share an example of inattentional blindness which was fortunately identified by reflex sentinel lymph node immunohistochemical protocols.

Top 10 Differential Diagnoses for Desmoplastic Melanoma.

BACKGROUND: Desmoplastic melanoma is a rare subtype of melanoma mainly appearing on sun-exposed skin. Clinically, it is many times non-pigmented and therefore the diagnosis is often not suspected. METHODS: Review article. RESULTS: In this paper we review the main histopathological, immunohistochemical, and molecular features of desmoplastic melanoma, as well as the top 10 morphologic differential diagnoses which should be considered in most cases. The histopathological pattern can be many times deceptive, mimicking a scar, a fibrous reaction, a fibrohistiocytic tumor such as a dermatofibroma, a vascular tumor such as angiosarcoma, a smooth muscle tumor such as leiomyosarcoma, or a neural tumor. Although an overlying atypical junctional melanocytic proliferation may be seen in most cases, it is absent in a significant percentage (up to 30%) of cases, making the diagnosis even more difficult in those instances. The range of diagnostic pitfalls is wide, which may present disastrous prognostic consequences. CONCLUSION: Desmoplastic melanoma is often a difficult diagnosis to make, as it frequently shows nonspecific clinical findings and overlapping histologic features with many other tumors. However, the potential clinical and prognostic consequences of misdiagnosis as another entity are great. Therefore, this diagnosis must always be kept in mind when encountering spindle cell tumors affecting the head and neck area.

Tertiary lymphoid structures in desmoplastic melanoma have increased lymphocyte density, lymphocyte proliferation, and immune cross talk with tumor when compared to non-desmoplastic melanomas.

Tertiary lymphoid structures (TLS) are ectopic lymphoid structures that can arise in human cancers and are associated with improved overall survival (OS) and response to immune checkpoint blockade (ICB) in several cancers, including non-desmoplastic metastatic melanoma (NDMM). Desmoplastic melanoma (DM) has one of the highest response rates to ICB, and we previously identified that primary DM (PDM) contains TLS. Despite the association of TLS with survival and ICB response, it is unknown whether TLS or associated markers of immune activity can differ between PDM and NDMM. We hypothesized that PDM would contain higher frequencies of TLS than NDMM, that T and B-cell densities and proliferation would be greater in TLS of PDM than TLS of NDMM, and that proliferation rates of T and B-cells in PDM TLS would be concordant with those of intratumoral lymphocytes. We found that four features of TLS in PDM distinguish them from TLS in NDMM. TLS were peritumoral in NDMM but intratumoral in PDM. CD8+ T-cell and CD20+ B-cell densities and proliferative fractions were higher in PDM TLS than NDMM TLS. Additionally, the proliferative fractions of T- and B-cells were concordant between the TLS and tumor site in PDM and discordant in NDMM. Collectively, these data suggest that TLS and associated immune markers can differ across melanoma subsets and suggest that PDM TLS may be more immunologically active and have enhanced immune cell trafficking between tumor and TLS compared to NDMM.

Representativeness of initial skin biopsies showing pure desmoplastic melanoma: implications for management.

Desmoplastic melanoma (DM) is an uncommon subtype of melanoma with distinct clinicopathological features. It is classified into pure desmoplastic melanoma (PDM) when the proportion of desmoplastic melanoma is ≥90% of the dermally-invasive component, and mixed desmoplastic melanoma (MDM) when the proportion of desmoplastic melanoma is <90%. Studies have reported a lower sentinel lymph node biopsy (SLNB)-positivity rate in PDM compared to MDM and non-DM. As a result, some have recommended not performing SLNB in PDM patients. When PDM is identified in a partial biopsy of a melanoma, there is a risk that sampling bias may under-recognise MDM, but to the best of our knowledge this has not been previously assessed or quantified. The aim of this study was to assess the concordance of the proportion of desmoplastic melanoma in an initial partial biopsy of PDM with the proportion in the entire tumour following complete excision, in patients with cutaneous melanoma. A secondary aim was to determine how frequently this potentially resulted in a patient not receiving a SLNB. Seventy-eight cases of cutaneous melanoma were identified from the Melanoma Institute Australia (MIA) database and 23 cases from the Memorial Sloan Kettering Cancer Centre (MSKCC), where an initial biopsy contained PDM and a subsequent wide excision had residual invasive melanoma. Clinicopathological features were analysed in all patients, including whether a SLNB was performed, the results of SLNB, and any subsequent recurrence. Ninety percent (91/101) of cases were still classified as PDM in the complete wide excision specimen while 10% (10/101) of cases were reclassified as MDM, which was a significant change in classification of final desmoplastic melanoma subtype (p<0.001). The proportion of desmoplastic melanoma was also significantly different between the initial and excisional biopsies (p=0.004). Forty-eight (48/101) patients had a SLNB, of which two (4.5%) were positive for metastatic melanoma; both cases were PDM in the excision specimen. Of the 10 cases demonstrating MDM in the excision specimen, the initial biopsy was a punch biopsy in six cases, shave biopsy in two cases and subcutaneous tissue was sampled in two patients (one punch biopsy, one incisional biopsy). Four of these 10 patients underwent SLNB which was negative in all cases. Twenty-two patients developed recurrence in the follow-up period (median 30 months, range 1-192 months), three with MDM in their excision specimen. One patient did not have a SLNB and developed regional lymph node recurrence. In this study there was a 10% risk that the percentage of desmoplastic melanoma in an initial biopsy of PDM was not representative of the entire lesion, resulting in reclassification as MDM in the excision specimen. If a SLNB is not performed in such cases, a positive SLNB may be missed (one patient in our study) which could impact treatment options for the patient. We recommend caution in not offering a SLNB in the setting of an initial biopsy of PDM if the biopsy is small compared with the overall lesion. If a SLNB is not procured at the time of wide excision in such cases, the SLNs should still be mapped by lymphoscintigraphy to facilitate careful follow up and to enable earlier detection and treatment of nodal disease.

Sentinel lymph node biopsy in desmoplastic melanoma - the percent desmoplastic component matters: A systematic review.

BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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. SUMMARY: 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.

Update on the Diagnosis and Management of Desmoplastic Melanoma. / Actualización en el diagnóstico y manejo del melanoma desmoplásico.

Desmoplastic melanoma (DM) accounts for 0.4% to 4% of all melanomas. These skin tumors are mainly formed by amelanotic spindled melanocytes immersed in an abundant collagen stroma and are classified as pure when the desmoplastic component accounts for at least 90% of the invasive tumor and as mixed or combined otherwise. DMs are more common in men (male to female ratio, 1.7 to 2:1), and the mean age at diagnosis is 66 to 69 years. The tumors tend to occur in chronically sun-exposed areas, often in association with lentigo maligna, and are difficult to recognize because they can resemble a scar, presenting as a firm, unpigmented papule or plaque with poorly defined borders. DMs also have a strong tendency to recur locally, and pure variants rarely spread to the lymph nodes. Nonetheless, recently published series suggest that patients with DM have a similar prognosis to those with nondesmoplastic melanoma of the same thickness. The clinical management of DM varies in certain aspects from that of other melanomas and is reviewed in this article.

Actualización en el diagnóstico y manejo del melanoma desmoplásico / Update on the Diagnosis and Management of Desmoplastic Melanoma

El melanoma desmoplásico (MD) representa entre el 0,4-4% de todos los melanomas. Se presenta como un tumor constituido predominantemente por melanocitos fusiformes amelanóticos inmersos en un estroma colágeno abundante. Se clasifica en MD puro o mixto, basándose en la proporción de melanoma desmoplásico frente a la del melanoma no desmoplásico presente en el tumor infiltrante. En el MD puro el componente desmoplásico representa más del 90% del melanoma infiltrante mientras que, en el MD combinado o mixto, el componente desmoplásico representa menos del 90%. El MD es más frecuente en varones (ratio 1,7-2:1); la edad media al diagnóstico oscila entre 66-69 años y suele localizarse en áreas de fotoexposición crónica, a menudo asociado a un lentigo maligno. Su reconocimiento clínico es difícil ya que se presenta como una pápula o placa no pigmentada, indurada y de bordes mal definidos, que recuerda a una cicatriz. El MD es un tumor con una alta tendencia a la recurrencia local y en el caso del MD puro, una baja tendencia a la diseminación ganglionar. Sin embargo, en las series más contemporáneas, su pronóstico global parece ser similar al de melanomas no desmoplásicos (MND) del mismo grosor. Su abordaje clínico posee algunos matices diferenciales, en comparación al resto de melanomas, que se revisan en el presente trabajo (AU)

Desmoplastic melanoma (DM) accounts for 0.4% to 4% of all melanomas. These skin tumors are mainly formed by amelanotic spindled melanocytes immersed in an abundant collagen stroma and are classified as pure when the desmoplastic component accounts for at least 90% of the invasive tumor and as mixed or combined otherwise. DMs are more common in men (male to female ratio, 1.7 to 2:1), and the mean age at diagnosis is 66 to 69 years. The tumors tend to occur in chronically sun-exposed areas, often in association with lentigo maligna, and are difficult to recognize because they can resemble a scar, presenting as a firm, unpigmented papule or plaque with poorly defined borders. DMs also have a strong tendency to recur locally, and pure variants rarely spread to the lymph nodes. Nonetheless, recently published series suggest that patients with DM have a similar prognosis to those with nondesmoplastic melanoma of the same thickness. The clinical management of DM varies in certain aspects from that of other melanomas and is reviewed in this article (AU)

[Translated article] Update on the Diagnosis and Management of Desmoplastic Melanoma / Actualización en el diagnóstico y manejo del melanoma desmoplásico

Desmoplastic melanoma (DM) accounts for 0.4% to 4% of all melanomas. These skin tumors are mainly formed by amelanotic spindled melanocytes immersed in an abundant collagen stroma and are classified as pure when the desmoplastic component accounts for at least 90% of the invasive tumor and as mixed or combined otherwise. DMs are more common in men (male to female ratio, 1.7 to 2:1), and the mean age at diagnosis is 66 to 69 years. The tumors tend to occur in chronically sun-exposed areas, often in association with lentigo maligna, and are difficult to recognize because they can resemble a scar, presenting as a firm, unpigmented papule or plaque with poorly defined borders. DMs also have a strong tendency to recur locally, and pure variants rarely spread to the lymph nodes. Nonetheless, recently published series suggest that patients with DM have a similar prognosis to those with nondesmoplastic melanoma of the same thickness. The clinical management of DM varies in certain aspects from that of other melanomas and is reviewed in this article (AU)

El melanoma desmoplásico (MD) representa entre el 0,4-4% de todos los melanomas. Se presenta como un tumor constituido predominantemente por melanocitos fusiformes amelanóticos inmersos en un estroma colágeno abundante. Se clasifica en MD puro o mixto, basándose en la proporción de melanoma desmoplásico frente a la del melanoma no desmoplásico presente en el tumor infiltrante. En el MD puro el componente desmoplásico representa más del 90% del melanoma infiltrante mientras que, en el MD combinado o mixto, el componente desmoplásico representa menos del 90%. El MD es más frecuente en varones (ratio 1,7-2:1); la edad media al diagnóstico oscila entre 66-69 años y suele localizarse en áreas de fotoexposición crónica, a menudo asociado a un lentigo maligno. Su reconocimiento clínico es difícil ya que se presenta como una pápula o placa no pigmentada, indurada y de bordes mal definidos, que recuerda a una cicatriz. El MD es un tumor con una alta tendencia a la recurrencia local y en el caso del MD puro, una baja tendencia a la diseminación ganglionar. Sin embargo, en las series más contemporáneas, su pronóstico global parece ser similar al de melanomas no desmoplásicos (MND) del mismo grosor. Su abordaje clínico posee algunos matices diferenciales, en comparación al resto de melanomas, que se revisan en el presente trabajo (AU)

An Unusual Case of Desmoplastic Melanoma With Monster Cells Imitating an Atypical Fibroxanthoma.

Numerous cells with very large and irregular nuclei ("monster" cells) have not hitherto been reported in desmoplastic melanoma (DM). Their prognostic significance in melanomas is a matter of debate, although some authors have associated them with more aggressive tumor behavior. We report a mixed DM on the scalp of an 88-year-old woman imitating an atypical fibroxanthoma. Tumor cells stained positive for SOX10, S100, and cyclin D1; BRAF mutation status was negative, and fluorescence in situ hybridization analysis showed copy number gains in 11q13 (cyclin D1) and 6p25 (RREB1), and loss in 6q23 (MYB). Cyclin D1 amplification is associated with poor prognosis in melanoma.

Evolution of superficial spreading melanoma to resemble desmoplastic melanoma: case report.

Desmoplastic melanoma commonly occurs on the head and neck in a pure form, but occasionally, it occurs in a mixed tumor with another type, usually superficial spreading melanoma (SSM), and rarely as a metastasis from a primary SSM. We report here a primary SSM on the leg of a 32-year-old male which metastasised to lymph nodes, and 10 years later recurred at the primary site initially with mixed features but evolving to resemble a uniformly desmoplastic, deeply invasive melanoma. This unusual case has implications for clinical management and is additionally notable for its reversal in behavior, from metastatic to local infiltrative type, correlating with the change in morphology.

Desmoplastic Melanoma: A Clinicopathological Analysis of Three Cases in the Chinese Population.

PURPOSE: To investigate the clinicopathological characteristics and immunophenotype of desmoplastic melanoma (DM) in the Chinese population. PATIENTS AND METHODS: We report three cases of DM diagnosed by the Pathology Department of Shanghai Dermatology Hospital. We describe the clinical and pathological characteristics of the three cases and examine molecular markers used in the diagnosis of DM. Finally, we summarize the current literature in the DM field. RESULTS: Clinically, lesions in the three DM patients were characterized by non-pigmented nodules or papules. Microscopically, we observed an abundance of fibrous interstitium mixed with spindle cells exhibiting various degrees of atypia. Occasionally, these structures exhibited changes in lentigo maligna at the epidermal junction, accompanied by the presence of lymphoid follicular structures and neurophilic behavior. Diagnosis of DM was confirmed by immunohistochemical staining, which revealed high expression levels of S-100 and SOX-10. Melanocyte markers were focally positive or negative. Unlike DMs from other populations, our three patients were negative for WT-1 and P53. All three cases received surgical resection, which is the preferred treatment for DM, and none of the patients experienced recurrence. CONCLUSION: DM in these Chinese patients was similar to that observed in other DM populations in terms of immunophenotype and clinical and histological features. A notable absence in p53 staining was observed in the three cases reported here, suggesting that p53 negativity should not exclude the diagnosis of DM in the Chinese population.

Perineuriomatous nevi: A series of eight cases highlighting unifying pathologic features to avoid misdiagnosis.

BACKGROUND: Perineuriomatous nevi are rare and diagnostically problematic. We report a series of eight perineuriomatous nevi to highlight the diagnostic features. METHODS: Cases were retrospectively reviewed and characterized. RESULTS: Median age was 42.5 years (range 25-64), with equal sex distribution. Lesions occurred on the arm (n = 4), trunk (n = 2), and head/neck (n = 2). Median size was 7.5 mm (range 5-12 mm). Clinical differential diagnoses included atypical nevus (3), blue nevus (1), neurofibroma (1), and dermatofibroma (1). Lesions were circumscribed, dome-shaped (5/8), and biphasic (8/8) with nested epithelioid cells and wavy spindled cells arranged in whorled fascicles in a myxocollagenous stroma. When present, junctional growth was lentiginous (4/8). No cases displayed pleomorphism or mitotic figures. The perineuriomatous component stained positively for epithelial membrane antigen (8/8 focal to diffuse) and CD34 (4/5 focal to diffuse). SOX10 and S100 protein stained all nevoid cells and in some cases a subset of intermingled spindled cells in perineuriomatous areas, where other melanocytic markers were negative. p16 protein expression was uniformly retained (3/3), and p53 negative (0/2). Nevoid cells in most lesions were positive for BRAFV600E (5/7). Ki67 was mildly elevated (~5%) in 3/3 cases. CONCLUSIONS: Recognizing the histopathologic and immunophenotypic features in these unusual nevi helps avoid overdiagnosis.

A Rare Case of Epithelioid Malignant Peripheral Nerve Sheath Tumor Mimicking Malignant Melanoma.

Malignant peripheral nerve sheath tumors are rare soft tissue sarcomas that are often associated with neurofibromatosis type-1. These tumors share common immunohistochemistry findings which can make diagnosis difficult. We present the case of a woman who presented with a diagnosis of metastatic melanoma of the index finger of her left hand but was eventually diagnosed with primary epithelioid malignant peripheral nerve sheath tumor. We will be highlighting the diagnostic challenge of differentiating between these two very different malignancies.