Soft Tissue Sarcoma Mimicking Melanoma: A Systematic Review

Cassalia, Fortunato; Cavallin, Francesco; Danese, Andrea; Fiore, Paolo Del; Prata, Claudia Di; Rastrelli, Marco; Fortina, Anna Belloni; Mocellin, Simone

doi:10.3390/cancers15143584

Cited by 4 publications

(7 citation statements)

References 39 publications

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“…Dermoscopy is very helpful in differentiating AAM from ALM; while the diagnosis of AAM may be based on subtle vascular patterns and the absence of pigmented structures, ALM may present with more definitive indicators of melanoma, such as pigment networks [5,8]. Another important aspect is the differentiation of AAM from other malignancies such as sarcomas, which may confuse the physician due to their tendency to involve similar acral sites [40,41]. The differentiation of AAM from sarcomas requires careful clinical evaluation, supported by histological and immunohistochemical analysis [40,42].…”

Section: Discussionmentioning

confidence: 99%

Misdiagnosis and Clinical Insights into Acral Amelanotic Melanoma—A Systematic Review

Cassalia,

Danese,

Cocchi

et al. 2024

JPM

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Background: Acral amelanotic melanomas (AAMs), a rare subset of melanomas located on acral sites such as the palms, soles, and subungual areas, are diagnostically challenging due to their lack of typical pigmentation and often benign clinical appearance. Misdiagnosis is common, leading to delays in treatment and potentially worse outcomes. This systematic review aims to synthesise evidence on cases of AAM initially misdiagnosed as other conditions, to better understand their clinical and epidemiological characteristics, diagnostic pitfalls, and management strategies. Methods: A comprehensive search of the MEDLINE/PubMed, EMBASE, and SCOPUS databases was conducted up to March 2024. Case reports and small case series of AAMs initially misdiagnosed as other conditions were included. Data on patient demographics, clinical presentation, and diagnostic methods were collected and analyzed. Results: Of the 152 records identified, 26 cases from 23 articles met the inclusion criteria. A demographic analysis revealed that the gender distribution appears to be perfectly balanced, with an age range of 38 to 91 years. Misdiagnoses included non-healing ulcers or traumatic lesions (37.5%), benign proliferative lesions (29.2%) and infectious lesions (20.8%). The foot was the most affected site (53.8%). Notably, a histological evaluation was performed in 50% of cases involving the upper extremities, in contrast to only 7.1% of cases involving the foot and 0% of cases of the heel. This discrepancy suggests a reluctance to perform biopsies in the lower extremities, which may contribute to a higher misdiagnosis rate in these areas. Conclusions: The underutilization of biopsy in the diagnosis of lower extremity lesions contributes significantly to the misdiagnosis and delay in treatment of AAMs. Especially when the clinical assessment and dermoscopy are inconclusive, biopsies of suspicious lesions are essential. Immunohistochemistry and markers such as PRAME are critical in differentiating melanoma from other malignancies such as clear cell sarcoma. This review highlights the need for increased vigilance and a proactive diagnostic approach to increase early detection rates and improve prognostic outcomes.

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Section: Discussionmentioning

confidence: 99%

Misdiagnosis and Clinical Insights into Acral Amelanotic Melanoma—A Systematic Review

Cassalia,

Danese,

Cocchi

et al. 2024

JPM

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“…Notably, several tumour types, including spindle cell lipoma and dermatofibrosarcoma protuberans, showed consistently negative PRAME expression. Furthermore, it could be useful in the differential diagnosis between melanoma and clear cell sarcoma (CCS) [59,61].…”

Section: Prame Expression In Soft Tissue Tumoursmentioning

confidence: 99%

“…The development of sensitive and specific assays to detect PRAME expression may be useful for selected diagnostic problems: the distinction of nevus from melanoma (in skin or lymph nodes) and the assessment of the margin clearance of melanomas, particularly in cases with a lentiginous in situ component such as seen in acral and lentigo maligna melanomas, enabling early intervention and improving patient outcomes [4]. It may be useful in the differential diagnosis between melanoma and some forms of sarcoma, such as clear cell sarcoma [44,61]. In addition to its diagnostic potential, PRAME is increasingly being recognised as a prognostic marker in melanoma [5].…”

Section: Implications For the Diagnosis And Prognosis Of Melanomamentioning

confidence: 99%

PRAME Updated: Diagnostic, Prognostic, and Therapeutic Role in Skin Cancer

Cassalia,

Danese,

Tudurachi

et al. 2024

IJMS

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Preferentially Expressed Antigen in Melanoma (PRAME), a member of the cancer/testis antigen family, is central to the field of skin cancer diagnostics and therapeutics. As a nuclear receptor and transcriptional regulator, PRAME plays a critical role in inhibiting retinoic acid signalling, which is essential for cell differentiation and proliferation. Its aberrant overexpression in various malignancies, particularly cutaneous melanoma, is associated with more aggressive tumour phenotypes, positioning PRAME as both a diagnostic and prognostic marker. In melanoma, PRAME is typically highly expressed, in contrast to its weak or absent expression in benign nevi, thereby improving the accuracy of differential diagnoses. The diagnostic value of PRAME extends to various lesions. It is significantly expressed in uveal melanoma, correlating to an increased risk of metastasis. In acral melanomas, especially those with histopathological ambiguity, PRAME helps to improve diagnostic accuracy. However, its expression in spitzoid and ungual melanocytic lesions is inconsistent and requires a comprehensive approach for an accurate assessment. In soft tissue sarcomas, PRAME may be particularly helpful in differentiating melanoma from clear cell sarcoma, an important distinction due to their similar histological appearance but different treatment approaches and prognosis, or in detecting dedifferentiated and undifferentiated melanomas. In non-melanoma skin cancers such as basal cell carcinoma, squamous cell carcinoma, and Merkel cell carcinoma, the variable expression of PRAME can lead to diagnostic complexity. Despite these challenges, the potential of PRAME as a therapeutic target in melanoma is significant. Emerging immunotherapies, including T-cell-based therapies and vaccines targeting PRAME, are being investigated to exploit its cancer-specific expression. Ongoing research into the molecular role and mechanism of action of PRAME in skin cancer continues to open new avenues in both diagnostics and therapeutics, with the potential to transform the management of melanoma and related skin cancers.

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“…In addition to MM, other differential diagnoses are made with Kaposi’s sarcoma and malignant peripheral nerve sheath tumor (MPNST). Kaposi’s sarcoma typically occurs in immunocompromised patients, while MPNST is often found in patients with neurofibromatosis type 1 [ 3 ].…”

Section: Introductionmentioning

confidence: 99%

“…This, combined with the fact that immunohistochemistry cannot distinguish between the two types of tumors, means that clear cell sarcoma is misdiagnosed as malignant melanoma. Due to CCS rarity, FISH and RT-PCR testing are essential for an accurate diagnosis [ 3 ]. Correct and rapid diagnostics are necessary for insuring the optimal therapeutic response and a better oncological outcome, and physicians should always consider genetic testing for CCS when faced with an MM diagnostic.…”

Section: Introductionmentioning

confidence: 99%

Intestinal Clear Cell Sarcoma—A Case Presentation of an Extremely Rare Tumor and Literature Review

Rotaru,

Chitoran,

Mitroiu

et al. 2024

Medicina

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Background: Clear cell sarcoma (CCS) is an extremely rare form of sarcoma representing less than 1% of all soft-tissue sarcomas. It has morphological, structural, and immunohistochemical similarities to malignant melanoma, affecting young adults and equally affecting both sexes, and is usually located in the tendinous sheaths and aponeuroses of the limbs. Gastrointestinal localization is exceptional, with less than 100 cases reported thus far. The gene fusion of activating transcription factor 1 (ATF1) and the Ewing sarcoma breakpoint region 1 (EWSR1) are pathognomonic for clear cell sarcoma, representing the key to the diagnosis. CCS is an extremely aggressive tumor, with >30% having distant or lymphatic metastasis at the time of diagnostic, and it has a high recurrence rate of over 80% in the first year after diagnosis and a high tendency for metastatic dissemination. Given the rarity of this tumor, there is no standardized treatment. Early diagnosis and radical surgery are essential in the treatment of CCS both for the primary tumor and for recurrence or metastasis. Chemo-radiotherapy has very little effect and is rarely indicated, and the role of targeted therapies is still under investigation. Case presentation: We present an extremely rare case of intestinal CSS in a 44-year-old Caucasian female. The patient, asymptomatic, first presented for a routine checkup and was diagnosed with mild iron-deficiency anemia. Given her family history of multiple digestive cancers, additional investigations were requested (gastroscopy, colonoscopy, tumoral markers and imaging) and the results were all within normal limits. In the subsequent period, the patient experienced mild diffuse recurrent abdominal pain, which occurred every 2–3 months. Two years later, the patient presented with symptoms of intestinal obstruction and underwent an emergency laparotomy followed by segmental enterectomy and regional lymphadenectomy for stenotic tumor of the jejunum. Histology, immunohistochemistry, and genetic testing established the diagnosis of CCS. No adjuvant therapy was indicated. Initially, no signs of recurrence or metastasis were detected, but after 30 and 46 months, respectively, from the primary treatment, the patient developed liver metastasis and pericolic peritoneal implants treated by atypical hepatic resections and right hemicolectomy. The patient remains under observation.

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Soft Tissue Sarcoma Mimicking Melanoma: A Systematic Review

Cited by 4 publications

References 39 publications

Misdiagnosis and Clinical Insights into Acral Amelanotic Melanoma—A Systematic Review

Misdiagnosis and Clinical Insights into Acral Amelanotic Melanoma—A Systematic Review

PRAME Updated: Diagnostic, Prognostic, and Therapeutic Role in Skin Cancer

Intestinal Clear Cell Sarcoma—A Case Presentation of an Extremely Rare Tumor and Literature Review

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