Blue Nevus Research Articles

Expression of Melan-A (MART-1) in Various Pigmented Melanocytic Nevi and Close Mimickers

Introduction: Melanocytic nevi are neoplasms resulting from the proliferation of melanocytes. Diagnosis of melanocytic tumours can be tricky, considering two factors,to diagnose origin and determination of its benign or malignant nature. Visualisation of melanin or other pigments are non specific with Hematoxylin and Eosin (H&E) staining and specific with Melan-A Immunohistochemistry (IHC). Intensity and pattern of these reactions shows marked variability in different melanocytic lesions. Aim: To study the intensity and pattern of Melan-A expression in various pigmented melanocytic nevi and to understand its utility to differentiate close mimickers. Materials and Methods: A cross-sectional study of 50 lesions (45 cases and 5 controls) was conducted in the Department of Pathology of Dr. B.R. Ambedkar Medical College (tertiary hospital), Bengaluru, Karnataka, India, between September 2020 to October 2021. The skin biopsies received were fixed in formalin and paraffin embedded. Sections were stained with H&E and Melan-A IHC marker, using A103 antibody and a high temperature antigen retrieval was performed. Pattern and intensity of Melan-A expression were studied and its evaluation was done with normal skin (control). Results: Melan-A showed varied intensity (+ weak; ++ moderate; +++ strong), pattern (patchy, diffuse), distribution and on various pigmented melanocytic lesions and mimickers were analysed. Dermal nevi (18) showed +++ diffuse pattern in dermis and two cases showed ++ moderate and patchy staining. Five cases of Compound nevi showed ++ intensity, diffuse pattern in Dermoepidermal Junction (DEJ) and dermis, Deep penetrating nevi (in one case) +++ intensity and diffuse pattern in DEJ, Dermis. Two cases of pigmented Basal Cell Carcinoma (BCC) showed + intensity and no definitive pattern in dermis. Four cases in fibrohistiocytic lesions and Malignant Peripheral Nerve Sheath Tumour (MPNST) shows negative Melan-A. In control melanocytes show dendritic pattern of staining and melanophages were negative. Conclusion: Melan-A is specific melanocytic marker as it stains only melanocytic lineage and no other cell types in background thus it is a marker of histogenesis instead of malignancy indicator. It highlights important architectural features and confirms the origin of lesions thus aiding the pathologist towards accurate diagnosis and differentiates from close mimickers.

A rare cause of recurrent gastrointestinal bleed: Blue rubber bleb nevus syndrome

Congenital venous malformations (VMs) are rare cause of gastrointestinal (GI) bleed in children. Blue rubber bleb nevus syndrome characterized by VMs in GI tract and skin affect at early age in life. Diagnosis is based on typical skin lesion and history of recurrent GI bleed. In this article, we presented a similar case of young girl with typical skin lesion and recurrent GI bleed requiring multiple blood transfusions presenting our department. She was subjected to surgical treatment and endoscopy therapy due to failure of conservative therapy. This case report depicts importance of typical clinical features of rare diseases.

Sinonasal blue nevus: a case report and review.

Blue nevus is a type of uncommon benign pigmented lesion in the skin or the mucosa of human body which is featured by pigmented dendritic melanocytes and spindled melanocytic cells. Sinonasal blue nevus is extremely rare. We reported a sinonasal blue nevus case with the background of pituitary adenoma, type 2 diabetes mellitus, and hypertension (including endoscopic and histological pictures). Further, the existing literature about blue nevus is reviewed. This paper puts a spotlight on the potential correlation between blue nevus with the endocrine system disorder and provides support for further experimental research.

Primary orbital melanoma arising in an atypical diffuse (plaque-like) blue naevus/melanocytosis: a case report and review of literature

BackgroundPrimary orbital melanoma is a rare disease and can occasionally develop from a pre-existing neoplasm of the blue naevus family of melanocytic lesions.Case presentationHerein we report a rare case of primary orbital melanoma arising from an unusual atypical diffuse (plaque-like) blue naevus/melanocytosis. A 27 year old man presented with mild pain and swelling of the left eye. Magnetic Resonance Imaging revealed a left lateral episcleral orbital mass and an incisional biopsy confirmed the diagnosis of malignant melanoma. Skin-sparing total left orbital exenteration was performed. Histopathological examination of the exenteration specimen revealed a primary orbital melanoma arising in a pre-existing blue naevus like melanocytosis.We demonstrate the evidence for histological progression, characterise the molecular profile of this tumour and discuss the related literature.ConclusionsThis case emphasises the importance of a meticulous clinicopathological correlation in recognising such a tumour as a primary orbital melanoma rather than a metastasis, which is managed differently.

Atypical cellular blue nevus: A case report and review of literature

Blue nevi are benign neoplasms of many variants which have several similar histological, clinical and immunochemical features. The two most frequent types are dendritic/common blue nevus and cellular blue nevus. Atypical blue nevus is a rare variant of cellular blue nevus whose characteristics are usually confused with malignant blue nevus/malignant melanoma which arise in a cellular blue nevus. Our paper describes a case of a 59-year-old woman who presented with a pigmented lesion in her right gluteal region which started itching and slowly grew in the last 20 years. After surgical resection, histopathological examination showed a nodule which had features that were consistent with atypical cellular blue nevus. Keywords: atypical; cellular; blue nevus.

Blue rubber bleb nevus syndrome: A rare cause of chronic gastro intestinal bleed in children

Blue rubber bleb nevus syndrome (BRBNS) is a rare congenital disorder presenting with multifocal venous malformations of the skin, soft tissues, and gastrointestinal (GI) tract. Here, we report a case of a 10-year-old girl who presented with recurrent lower GI bleeding and abdominal pain requiring repeated blood transfusion for 2 years. A contrast computed tomography showed multiple cavernous haemangiomas in the liver, oesophagogastroduodenoscopy and colonoscopy showed multiple hemangiomas from esophagus to large bowel. Her molecular pathology confirmed BRBNS. She underwent endoscopic argon plasma coagulation with uneventful recovery. In spite of a wide range of therapeutic options for the management of BRBNS described in the literature, the efficacy of those available therapies, including surgical excision, is not well established.

Research progress on primary orbital melanoma

Primary orbital melanoma (POM) is a sort of extremely rare orbital malignancy. It often associates with melanin lesion such as congenital ocular melanocytosis and blue nevus. The most common clinical manifestation of POM is progressive painless proptosis. There are some difficulties in diagnosing this disease. MRI shows characteristic expression of this disease as an important way to diagnose POM, while pathology is the gold standard. Surgery is the mainstay of treatment in patients with POM. In addition, adjuvant radiotherapy and chemotherapy should be considered. This article systematically reviews the research progress of pathogenesis, clinical manifestation, auxiliary examination, differential diagnosis and treatment of POM, in order to provide some thoughts for the future study of the rare malignancy. (Chin J Ophthalmol, 2021, 57: 861-864).

Blue rubber bleb nevus syndrome: a single-center case series in 12 years.

BackgroundBlue rubber bleb nevus syndrome is a rare congenital disease characterized by multiple venous malformations in skin and gastrointestinal tract, not all patients have typical cutaneous lesions, refractory anemia may be the only clinical symptom, it is easy to miss diagnosis.MethodsA retrospective single center study was conducted on 8 patients with blue rubber bleb nevus syndrome from 2009 to 2021. Data were analyzed including clinical feature, diagnostic workup and results, gene detection, treatment and follow-up.ResultsFive children (62.5%) developed the disease in infancy, which initial symptoms were all cutaneous venous malformations. All children had chronic refractory anemia and gastrointestinal bleeding. Cutaneous lesions were observed in 87.5%, 1 child had multiorgan involvement. Gastrointestinal venous malformations were observed in 100%, lesions were more common in small intestine than in stomach or colon. No somatic mutation in TEK was found in our children. Diagnostic interval was on average 4.7 years. Eighty-seven-point-five percent children received at least one endoscopic or surgical intervention, however, those methods could not eradicate all the lesions and prevent relapse. Two children treated with sirolimus for more than 8 years, only 1 have satisfactory therapeutic effect. Besides, I child has growth retardation and emotional problems during follow-up.ConclusionsBlue rubber bleb nevus syndrome needs to be considered when find bluish nodular cutaneous lesions, chronic anemia or gastrointestinal bleeding of unknown origin. Capsule endoscopy is the most sensitive in diagnosing of this disease. Oral sirolimus at a relatively low dosage is effective, further comprehensively studies are required to evaluation of its efficacy, safety and the optimal dosage about the children.

Venous Malformations in Childhood: Clinical, Histopathological and Genetics Update.

Our knowledge in vascular anomalies has grown tremendously in the past decade with the identification of key molecular pathways and genetic mutations that drive the development of vascular tumors and vascular malformations. This has led us to better understand the pathogenesis of vascular lesions, refine their diagnosis and update their classification while also exploring the opportunity for a targeted molecular treatment. This paper aims to provide an overview of venous malformations (VM) in childhood. Specific entities include common VMs, cutaneo-mucosal VM, blue rubber bleb nevus syndrome or Bean syndrome, glomuvenous malformation, cerebral cavernous malformation, familial intraosseous vascular malformation and verrucous venous malformation. The clinicopathological features and the molecular basis of each entity are reviewed.

033 Excision of halo nevus without PD-L1 expression may cure vitiligo

Halo nevus (HN), also called Sutton nevus, is a nevus cell nevus that is surrounded by vitiligo and is caused by a T-cell mediated immune response to the nevus antigen. Excision of nevus is recommended to prevent progression to vitiligo vulgaris. When vitiligo may occur around malignant melanoma, hemangioma, blue nevus, neurofibroma, senile wart, etc, it’s called Sutton’s phenomenon. Especially, vitiligo in melanoma patients is called “melanoma-associated vitiligo” and recognized to associate with favorable outcomes. It’s sometimes observed in patients who respond to immune checkpoint inhibitor (ICI) therapy as a “preferable” immune-related adverse event (irAE), the mechanism has attracted attention. However, there are few reports on analyses of immune checkpoint including PD-1/PD-L1 in HN. In the present study, to evaluate the relationship between immune checkpoint including PD-1/PD-L1 and HN, we performed immunohistochemical analysis using formalin-fixed paraffin-embedded (FFPE) samples collected from 38 HN patients (16 males and 22 females, mean age 20.47 years) whose nevus were resected in Nagoya City University Hospital. Of the 29 cases that we were able to follow after nevus excision, 12 cases showed improvement of the surrounding vitiligo and 17 cases showed no change or expansion of vitiligo. 25 cases have vitiligo vulgaris, and 10 of them showed improvement of vitiligo vulgaris after HN excision. Immunohistochemical findings showed that PD-L1 expression was positive in 25 of 36 cases, and cases with improved vitiligo after nevus excision were predominantly PD-L1 negative. PD-1 expression in infiltrating cells was positive in 19 of 38 patients, but there was no significant correlation between PD-1 expression and improvement of vitiligo. These results suggest that more than local immune responses are involved in vitiligo formation in PD-L1-positive HN, and the analysis of immune responses in PD-L1-positive HN may lead to elucidation of the mechanisms of tumor immunity and irAEs

Diagnosis and Management of Melanoma of the Scalp: A Review of the Literature.

Cutaneous melanoma is a public health issue and the head and neck region is of particular interest, despite accounting for only 9.0% of the total body surface, it harbours 20% of melanoma cases. Data from the literature show that scalp melanomas (SM) carry high mortality rates, with a 10-year survival rate of 60% which lead them to be named as the “invisible killer”. Moreover, SMs are more common in the elderly than in young population, and they occur six times more frequently in men than in women. This is probably related to the higher incidence of androgenetic alopecia and a higher cumulative and intermittent ultraviolet damage on the scalp. Histologically, SM is a heterogenous group, including lentiginous melanoma (LM), desmoplastic melanoma, superficial spreading and nodular melanoma. Thin melanomas tend to display an atypical network or pseudo-network and regression in dermoscopy. Blue-white veil, irregular pigmented blotches and an unspecific pattern are most commonly detected in thick lesions. On reflectance confocal microscopy (RCM), the most frequent pattern is irregular meshwork, but also ringed and disarranged pattern have been described. Differential diagnosis includes benign solar lentigo, actinic keratoses, lichen planus like keratosis, melanocytic nevi and blue nevi. All suspicious lesions should be biopsied; therefore, an excisional biopsy with 2 mm margins is usually the best option. The management of SM is the same as for melanoma on other body sites. However, sentinel node biopsy tends to be more challenging, as well as achieving adequate excision margins of the primary tumor. In this review, we summarize clinical, pathologic, dermoscopic and RCM features of SM, and focus on its epidemiology, risk factors and best management options.

Gastrointestinal Bleeds.

Gastrointestinal Bleeds.

Blue Rubber Bleb Nevus Syndrome Complicated by Enhanced-Fibrinolytic-Type DIC: A Case Report.

A 54-year-old Japanese man was diagnosed with blue rubber bleb nevus syndrome (BRBNS) due to venodilation in the lower extremities at birth and gastrointestinal vascular malformations. He also had small bowel bleeding and enhanced-fibrinolytic-type disseminated intravascular coagulation (DIC). Endoscopic sclerotherapy for intestinal hemangioma could not be performed because of bleeding concerns; instead, a combined anticoagulant and antifibrinolytic treatment was performed. Although combination treatment with unfractionated heparin and tranexamic acid proved ineffective for small bowel bleeding, combination treatment with apixaban and tranexamic acid dramatically improved enhanced-fibrinolytic-type DIC. In BRBNS, treatment strategies should be considered after performing detailed coagulation tests.

Dermatological and endocrine elements in Carney complex (Review).

Carney complex (CΝC) is a very rare, autosomal dominant, hereditary syndrome. Seventy percent of individuals with CNC have germline inactivating or deleting mutations of the CNC1 gene [currently known as protein kinase cAMP-dependent type I regulatory subunit α (PRKAR1A), located at the 17q22-24 chromosome level], with 30% of cases presenting with phosphodiesterase gene mutations. A member of the lentiginosis family, dermatological features include: skin pigmentation, cutaneous/mucosal myxomas, usually diagnosed by the age of 20 years (neonatal presentation is exceptional, requiring a meticulous differential diagnosis). Melanocyte-derived tumors such as epithelioid blue nevi (with different levels of pigmentation) and pigmented epithelioid melanocytoma (previously 'animal-type melanoma') are often found. Myxomas, mesenchymal tumors with mostly a benign pattern, may be recurrent. Primary cutaneous melanotic schwannoma are atypical, while non-skin sites are frequent. Corticotropinomas or somatotropinomas are part of the hereditary syndrome-related pituitary adenomas (representing 5% of all). Primary pigmented nodular adrenocortical disease involves bilateral cortical hyperplasia causing Cushing syndrome (CS) at an earlier age than non-CNC cases; osteoporotic fractures seem more prevalent compare to CS of other etiologies. Typically benign, a few cases of adrenocortical carcinoma have been identified. A total of 5% of familial non-medullary thyroid cancer is syndromic, also including CNC. CNC-related thyroid frame includes: hyperthyroidism, follicular hyperplasia/adenomas, follicular carcinoma (usually aggressive, bilateral or multifocal). Large cell calcifying Sertoli cell tumors of the testes have malignant behavior in adults; in children these may induce precocious puberty. Two particular mammary tumors are found: myxoid fibroadenomas and breast myxomatosis. Cutaneous/subcutaneous lesions, pigmented or not, or any focal swelling of non-identified cause needs careful examination, since dermatological elements are among the earliest and most discernable by which to detect lesions in CNC, a systemic condition with multi-level endocrine involvement.

Melanositik lezyonlarda p16 ve CD117 ekspresyonunun önemi

Aim: The present study aims to determine the p16 and CD117 expression profiles of melanocytic lesions to investigate immune profiles that may facilitate differential diagnosis of melanoma from benign or potential precursor melanocytic lesions.Materials and Methods: Immunohistochemistry for p16 and CD117 was applied in a total of 81 cases with melanocytic lesions.Results: A significant loss of p16 expression was found in melanoma cases compared to benign and precursor melanocytic lesions (p<0.05). Moreover, a significant loss of p16 expression was also noted in cases of dysplastic nevus compared to those with intradermal nevus (p<0.01). While no CD117 expression was observed in intradermal nevi, high-level expression was seen in cases with Spitz nevus, blue nevus, invasive melanoma and dysplastic nevus (p<0.01).Conclusion: We believe using p16 and CD117 together may provide an important marker combination to aid in distinguishing melanoma from benign lesions and benign lesions from potential precursor melanocytic lesions.

28423 Treatment of cutaneous lesions in patient with blue rubber bleb nevus with diode laser

Blue rubber bleb nevus (BRBN) is a rare congenital skin disorder characterized by numerous, diffuse venous malformations of the cutaneous. The treatment of cutaneous lesions is not usually required except for cosmetic purposes while previous methods to remove cutaneous lesions including ND:YAG laser, photocoagulation, sclerotherapy, surgery often could lead to scars. We report a case of BRBN who had a good response to diode laser without adverse effects. A 16-month-old girl presented to our hospital with multiple, discrete, dark blue to violaceous soft compressible nodules on the skin as well as palm and sole. Especially, a large violaceous perianal lesion was about 4 cm in diameter that was at high risk for hemorrhage due to an anal fissure making the children occasionally bleeding while a bowel movement. Most of the lesions presented at birth remained stable in size and number. Abdominal ultrasound has not been discovered any abnormalities. Histopathology image of the cutaneous lesion shows variably sized, irregular and thin-walled vessels lined by a single layer of endothelial cells in the dermis. Immunohistochemical stain demonstrates endothelial cells positive for CD31. The girl has been treated using 810-nm diode laser at the setting 30-35 J/cm2, 30 ms for the cutaneous lesions on her back when the diagnosis of BRBN was established. After four times of treatment, a significant reduction in color and size was achieved on the back cutaneous lesions without adverse effects. In conclusion, this is the case of BRBN showing a good response to diode laser.

Endovascular treatment of an inferior vena cava aneurysm in a patient with blue rubber bleb nevus syndrome.

In 2017, an 18-year-old male patient with a previous diagnosis of blue rubber bleb nevus syndrome (BRBNS; A) and an asymptomatic inferior vena cava (IVC) saccular aneurysm was referred to our department, because of sudden unrelievable abdominal pain, which was considered related to aneurysm growth compared with the computed tomography examination 2 years previously (aneurysm size, 45 mm × 38 mm vs 65 × 61 mm; B1 and B2). The critical cardiopulmonary conditions related to BRBNS and the necessity of placing the incision through the diffuse cutaneous venous malformation were contraindications to open surgery.

Primary Cilia Are Preserved in Cellular Blue and Atypical Blue Nevi and Lost in Blue Nevus-like Melanoma.

Distinguishing cellular blue nevi (CBNs) and atypical CBNs from blue nevus-like melanoma (BNLM) can be diagnostically challenging. Immunohistochemistry may inform the diagnosis in a subset of cases but is not always diagnostic. Further, ancillary molecular testing is expensive and often requires significant tissue to complete. Primary cilia are cell-surface organelles with roles in signal transduction pathways and have been shown to be preserved in conventional melanocytic nevi but lost in melanoma. Immunofluorescence staining of primary cilia can be performed using a single standard-thickness formalin-fixed paraffin-embedded tissue section and has a turnaround time similar to immunohistochemistry. The percentage of tumoral melanocytes retaining a primary cilium is quantified and reported as the ciliation index. In the current study, we explored the utility of the ciliation index in a series of 31 blue nevus-like lesions, including CBNs (12), atypical CBNs (15), and BNLM (4). The average ciliation index for the CBNs was 59±18%, with a median of 60 (range: 28 to 87). The average ciliation index for atypical CBNs was 59±23, with a median of 59 (range: 20 to 93). The average ciliation index for BNLM was 4±3, with a median of 3 (range: 1 to 8). There was no significant difference in ciliation index between the CBN and atypical CBN categories. There was a significant difference between CBN and BNLM and between atypical CBNs and BNLM (P<0.001 for each). Here, we show that ciliation index is a quantitative diagnostic tool useful in the setting of blue nevus-like neoplasms, with benefits including cost and time efficiency.

Histopathologic classification and prognostic factors of melanoma: a 2021 update.

Despite the rapid recent advances in molecular analysis of tumors, which allow large-scale and high-resolution genomics, the "gold standard" for melanoma diagnosis continues to be histopathology, in conjunction with clinical characteristics and sometimes with important support of immunohistochemistry. Observations, where postulated that cutaneous melanomas may arise through two distinct pathways, discoveries such as that BRAFV600E mutations were mostly common in melanomas on sun-exposed skin with little solar elastosis and seminal works for melanoma progression and evolution set the groundwork for the new WHO Classification of Melanoma: a classification of melanoma that not only encompasses histologic but also clinical, epidemiologic, and genetic characteristics. The melanomas were divided into those etiologically related to sun exposure and those that are not, based on their mutational signatures, anatomic site, and epidemiology. On the basis of degree of associated solar elastosis melanomas on the sun exposed skin were further divided by the histopathologic degree of cumulative solar damage (CSD) of the surrounding skin, into low and high CSD. On the low-CSD group of melanomas are included superficial spreading melanomas, while the high-CSD melanomas encompasses lentigo maligna and desmoplastic melanomas. The "non-CSD" classification includes acral melanomas, some melanomas in congenital nevi, melanomas in blue nevi, Spitz melanomas, mucosal melanomas, and uveal melanomas. Nodular and nevoid melanoma may occur in any pathway. A group of intermediate tumors termed melanocytoma is proposed for tumors that in addition to mutations that activate the MAPK pathway, harbor multiple driver mutations, and they are either low-grade or high-grade, to indicate that they may carry a higher risk of malignant transformation. In this review a summary of the most recent WHO classification of melanoma is provided. A short analysis of essential histopathologic prognostic parameters is also provided. The new classification of melanoma discriminates distinct types of melanoma based on their clinicopathologic, and genomic characteristics. Undoubtedly, melanoma research will continue to evolve as new clinical, pathological, molecular data accumulates. The challenge of the forthcoming years is to better characterize the intermediate category of melanocytic lesions.

DP09: Blue rubber bleb naevus syndrome: an unusual case of a vascular anomaly presenting with a cutaneous manifestation and underlying gastrointestinal bleeding

DP09: Blue rubber bleb naevus syndrome: an unusual case of a vascular anomaly presenting with a cutaneous manifestation and underlying gastrointestinal bleeding