Differential Expression of Cancer Testis Antigens on Lentigo Maligna and Lentigo Maligna Melanoma

Tio, Darryl; Willemsen, Marcella; Krebbers, Gabrielle; Kasiem, Fazira R; Hoekzema, R.; Doorn, Remco van; Bekkenk, Marcel W.; Luiten, Rosalie M.

doi:10.1097/dad.0000000000001607

Cited by 29 publications

(46 citation statements)

References 9 publications

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“…Hence, immunohistochemical expression of PRAME may be useful to distinguish benign from malignant melanocytes. 14,15 In contrast to conventional nevi, we have occasionally observed NHP showing loss of HMB45 gradient and presence of HMB45 positive melanocytes in the deep dermis. To our knowledge, the use of PRAME immunohistochemistry has not yet been reported in NHP.…”

Section: Immunohistochemistrymentioning

confidence: 62%

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Aberrant expression of HMB45 and negative PRAME expression in halo nevi

Ruby

Yan

2020

J Cutan Pathol

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Background: Traditionally, most cutaneous nevi show a gradient of HMB45 (human melanoma black 45) and negative PRAME (preferentially expressed antigen in melanoma) immunostaining, while melanomas often show irregularly positive, diffusely positive or completely negative HMB45 expression, and PRAME immunopositivity. However, we have occasionally observed benign halo nevi with loss of HMB45 gradient, raising diagnostic consideration for melanoma. The purpose of this study was to elucidate the expression pattern of HMB45 and PRAME in nevi with the halo phenomenon (NHP). Methods: PRAME and HMB45 staining patterns in 20 cases of NHP and 16 cases of conventional nevi were evaluated using light microscopy. An HMB45 gradient was defined as immunopositivity in only superficial melanocytes. HMB45 aberrant expression consisted of superficial and deep immunopositivity. Results: Aberrant HMB45 expression was observed in 10 of 20 NHP (50%). A gradient of HMB45 staining was seen in most conventional nevi, with only one showing focal weak expression in the deep dermis (6.3%). All cases of NHP and conventional nevi showed essentially negative immunostaining by PRAME. Conclusion: Aberrant HMB45 expression in NHP is not uncommon and may be a diagnostic pitfall. Negative PRAME immunostaining may be a reassuring finding to help differentiate halo nevus from malignant melanoma.

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Section: Immunohistochemistrymentioning

confidence: 62%

“…Recent studies have shown that PRAME is diffusely expressed in the vast majority of non‐desmoplastic melanomas and PRAME expression is rare in melanocytic nevi. Hence, immunohistochemical expression of PRAME may be useful to distinguish benign from malignant melanocytes 14,15 …”

Section: Introductionmentioning

confidence: 99%

Aberrant expression of HMB45 and negative PRAME expression in halo nevi

Ruby

Yan

2020

J Cutan Pathol

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“…A small series of LM ( n = 8) by Tio et al . showed that PRAME is expressed in 75% of LM, whereas the other members of the CTA family did not show expression in LM by IHC 9 . A second case–series of margin assessment in 10 cases of MIS by PRAME expression demonstrated that PRAME showed a good correlation with margin assessment, as determined by both H&E and SOX10 18 .…”

Section: Discussionmentioning

confidence: 93%

“…Preferentially expressed antigen in melanoma (PRAME) is a cancer‐associated antigen that has been shown to be up‐regulated in melanoma, as well as acute leukaemia, neuroblastoma, breast carcinoma, renal cell carcinoma and multiple types of sarcoma 1–8 . Because PRAME is a member of the cancer testis antigen (CTA) family and shows absent to minimal expression in normal human tissues, with the exception of high expression in the testis and moderate expression in the ovary, adrenal gland and endometrium, it is an ideal target for immunotherapy 9 . Immunohistochemistry (IHC) for PRAME may also serve as an aid to diagnosis of difficult melanocytic lesions due to its specificity for malignant melanocytic lesions, with only rare staining in benign lesions (< 10% of cases) 8 .…”

Section: Introductionmentioning

confidence: 99%

PRAME immunohistochemistry as an adjunct for diagnosis and histological margin assessment in lentigo maligna

et al. 2021

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Aims Lentigo maligna (LM), the most common type of melanoma in situ, is a diagnostically challenging lesion for pathologists due to abundant background melanocytic hyperplasia in sun‐damaged skin. Currently, no laboratory methods reliably distinguish benign from malignant melanocytes. However, preferentially expressed antigen in melanoma (PRAME) has shown promise in this regard, and could potentially be applied to diagnosis and margin assessment in difficult cases of LM. Methods and results Ninety‐six cases with a diagnosis of LM (n = 77) or no residual LM (n = 19) following initial biopsy were identified and stained with an antibody directed towards PRAME. Immunohistochemistry (IHC) was scored as positive or negative, and measurement of histological margins by PRAME was performed and compared to the measurement of histological margins using conventional methods [haematoxylin and eosin (H&E) and/or sex‐determining region Y‐box 10 (SOX10) and/or Melan‐A]. Of cases with LM, 93.5% (72 of 77) were PRAME+ and 94.7% (18 of 19) of cases with no residual LM were PRAME–. Of the 35 cases with no margin involvement by PRAME or conventional assessment, 14 cases (40.0%) had no difference in measurement, 17 (48.6%) had a difference of 1 mm or less and four (11.4%) differed by between 1 and 3.5 mm. There was a high correlation between margin assessment methods (r = 0.97, P < 0.0001). Conclusions PRAME IHC is a sensitive (93.5%) and specific (94.7%) method for diagnosing LM on biopsy and excision, and measurement of histological margins by PRAME shows a high correlation with conventional methods for margin assessment. Furthermore, the nuclear expression of PRAME makes it a good target for use in dual‐colour IHC stains.

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“…LM should be distinguished from atypical melanocytic hyperplasia (solar melanocytosis), which is often found in chronically sun-exposed skin of the face; this differentiation may be difficult, particularly in early LM. Immunostaining for the cancer testis antigen, PRAME, seems to be a promising tool to this effect (24).…”

Section: Introductionmentioning

confidence: 99%

Treatment of lentigo maligna (Review)

Kanitakis

2021

World Acad Sci J

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Lentigo maligna (LM) is the most common type of in situ melanoma, usually appearing on chronically sun-exposed skin (mostly the head and neck) of elderly patients. It manifests clinically as a macule with a heterogeneous pigmentation and irregular contours. LM grows gradually over the years in a radial pattern and may eventually progress with a vertical growth phase, thereby transforming into an invasive melanoma (LM melanoma) that has potential for metastasis and a lethal outcome; accordingly, LM is currently regarded as an authentic melanoma in situ, rather than a premalignant condition. To the best of my knowledge, no prospective, randomized controlled studies evaluating the efficacy of the various treatment modalities applied for the treatment of LM exist to date. Surgical excision with tumour-free margins is regarded as the most effective treatment, achieving optimal rates of tumour clearance. Excision can be performed as traditional, one-step tumour ablation with predefined safety margins or, preferably, with margin-controlled techniques, such as staged excision or Mohs micrographic surgery, the latter methods achieving the highest cure rates. In the case of surgically-unresectable tumours or in frail patients with severe comorbidities, alternative non-surgical (off-label) therapies can be applied, including namely radiotherapy and imiquimod, as monotherapy or in various combinations.

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Differential Expression of Cancer Testis Antigens on Lentigo Maligna and Lentigo Maligna Melanoma

Cited by 29 publications

References 9 publications

Aberrant expression of HMB45 and negative PRAME expression in halo nevi

Aberrant expression of HMB45 and negative PRAME expression in halo nevi

PRAME immunohistochemistry as an adjunct for diagnosis and histological margin assessment in lentigo maligna

Treatment of lentigo maligna (Review)

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