ABSTRACT
A 25-year-old female Carney complex patient with a PRKAR1A mutation who had undergone surgery to remove teratomas visited our dermatology department. She was suspected of having a malignant melanoma in a teratoma. On clinical examination, a black nodule was found within the cyst. On histopathological examination, the black lesion was composed of heavily pigmented round cells with vesicular nuclei and single prominent nucleoli. Additionally, there were large cells with irregularly shaped nuclei. Upon immunohistochemical examination, the large, irregularly shaped cells were positively stained with Melan A, HMB45, S-100 protein, SOX10, CD10 (focally), and BRAFV600E , but negatively stained with PRAME. Based on the histopathological features, we diagnosed the patient with pigmented epithelioid melanocytoma (PEM) in a teratoma of a Carney complex patient. This is the first case of PEM developing from a teratoma. Since PEM lesions may spread to regional lymph nodes, careful follow-up is necessary.
Subject(s)
Carney Complex , Melanoma , Skin Neoplasms , Teratoma , Female , Humans , Adult , Carney Complex/diagnosis , Skin Neoplasms/pathology , Mutation , Teratoma/diagnosis , Antigens, NeoplasmABSTRACT
PURPOSE: Acquired melanocytic nevi are common eyelid lesions; however, their clinical presentation is not well documented. METHODS: In this retrospective study, clinical records were reviewed in patients evaluated between 2005 and 2022. RESULTS: Eyelid margin nevi (n = 150) were more commonly excised in female (78%) and Caucasian (86%) patients. Change in appearance/size were frequent presenting complaints, and 17% experienced ocular symptoms. Referring diagnosis included other benign lesions (11.3%), and concern for malignancy (16.7%). Many individuals (38.7%) noted their lesion for ≤5 years. Nevi were distributed across the 4 margins (9% peripunctal), and 88% had a regular base. Visible pigmentation was more common in non-Caucasians (95.2%) than Caucasians (41.1%). Lashes grew through 60.7% of nevi and were often misdirected.Nevi were treated with superficial excision and cauterization. Histologic subtypes included: dermal (86.6%), compound (9.4%), blue (2.7%), junctional (0.7%), lentiginous dysplastic (0.7%). An irregular base (p=0.042) and pigmentation (p=0.056) were more common in compound than dermal nevi. Lash line quality and appearance were improved in the majority of patients returning for follow-up, although postoperative trichiasis, marginal erythema, and residual pigmentation were observed. CONCLUSIONS: Melanocytic nevi commonly involve the eyelid margins and have a variety of presentations and appearances. Existing nevi can change, and new lesions appear throughout adulthood. Stable, benign appearing nevi can be observed. Shave excision provides a diagnosis and improved appearance for symptomatic or suspicious lesions, with few serious complications. Malignant transformation is rare, although evidence for recurrence warrants further evaluation.
Subject(s)
Eyelid Neoplasms , Nevus, Pigmented , Nevus , Skin Neoplasms , Humans , Female , Adult , Retrospective Studies , Nevus/pathology , Nevus/surgery , Nevus, Pigmented/surgery , Nevus, Pigmented/pathology , Eyelid Neoplasms/surgery , Eyelid Neoplasms/pathology , Eyelids/surgery , Eyelids/pathology , Skin Neoplasms/surgery , Skin Neoplasms/pathologyABSTRACT
Fusion genes involving homologs of protein kinase C (PKC) have been identified in a variety of tumors. We report the clinical and histologic presentation of 51 cutaneous melanocytic neoplasms with a PKC fusion gene (involving PRKCA in 35 cases, PRKCB in 15 cases, and PRKCG in a single case). Most tumors were in young adults (median age, 29.5 years; range, 1-73 years) but some presented in newborns. Histologically, 42 tumors were classified as benign, presenting predominantly as biphasic dermal proliferation (88%) with nests of small melanocytes surrounded by fibrosis with haphazardly arranged spindled and dendritic melanocytes, resembling those reported as "combined blue nevi." Most tumors (60%) were heavily pigmented and in 15%, hyperpigmented epithelioid melanocytes were present at the dermoepidermal junction. Two lesions were paucicellular and showed marked sclerosis. Three tumors, including 2 proliferating nodules, were considered intermediate grade. Six tumors had sheets of atypical melanocytes infiltrating the dermis and were classified as melanomas. Two of the melanomas displayed loss of BAP1 nuclear expression. The median follow-up time was 12 months, with 1 patient alive with metastatic disease and 1 dying of their melanoma. These results suggest that melanocytic tumors with PKC fusion genes have characteristic histopathologic features, which are more similar to blue nevi than to pigmented epithelioid melanocytomas. As is the case with GNA-mutated blue nevi, they can progress to melanomas via BAP1 inactivation and metastasize.
Subject(s)
Melanoma , Nevus, Blue , Skin Neoplasms , Infant, Newborn , Young Adult , Humans , Adult , Nevus, Blue/genetics , Biomarkers, Tumor/genetics , Melanoma/pathology , Skin Neoplasms/genetics , Skin Neoplasms/pathology , Protein Kinase C/geneticsABSTRACT
Activating mutations in GNAQ, GNA11, CYSLTR2, and PLCB4 genes are regarded as the main oncogenic drivers of blue nevi (BN) and blue malignant melanocytic tumors. Here we report 4 cases of blue melanocytic neoplasms devoid of these mutations but harboring GRM1 gene fusions. In this short series, there was no gender predominance (sex ratio, 1). The mean age at diagnosis was 40 years (range, 12-72). Tumors were located on the face (n = 2), forearm (n = 1), and dorsum of the foot (n = 1). Clinically, a plaque-like pre-existing BN was found in 2 cases, including a deep location; another case presented as an Ota nevus. Two cases were diagnosed as melanoma ex-BN, one as an atypical BN, and one as a plaque-like BN. Microscopic examination revealed a dermal proliferation of dendritic melanocytes in a sclerotic stroma. A dermal cellular nodule with atypia and mitotic activity was observed in 3 cases. Genetic investigation by whole exome RNA sequencing revealed MYO10::GRM1 (n = 2) and ZEB2::GRM1 (n = 1) fusions. A GRM1 rearrangement was identified by fluorescence in situ hybridization in the remaining case. SF3B1 comutations were present in the 2 melanomas, and both had a MYO10::GRM1 fusion. Array comparative genomic hybridization was feasible for 3 cases and displayed multiple copy number alterations in the 2 melanomas and limited copy number alterations in the atypical BN, all genomic profiles compatible with those of classical blue lesions. GRM1 was overexpressed in all cases compared with a control group of blue lesions with other typical mutations. Both melanomas rapidly developed visceral metastases following diagnosis, with a fatal outcome in one case and tumor progression under palliative care in the other. These data suggest that GRM1 gene fusions could represent an additional rare oncogenic driver in the setting of BN, mutually exclusive of classical canonical mutations, especially in plaque-type or Ota subtypes.
ABSTRACT
A 3-year-old boy presented with bluish patch and scattered blue spots on the left side of his face. After several sessions of laser treatment, the azury patch in the periorbital area became even darker. Histopathology showed many bipolar, pigment-laden dendritic cells scattered in the papillary and upper reticular dermis. Immunohistochemically, these cells were positive for S100, SOX-10, melan-A, P16, and HMB-45. The positive rate of Ki-67 was less than 5%. Finally, the lesion was diagnosed with nevus of Ota concurrent with common blue nevus. Therefore, for cases of the nevus of Ota with poor response to laser treatment, the possible coexisting diseases should be suspected.
Subject(s)
Nevus of Ota , Nevus, Blue , Skin Neoplasms , Male , Humans , Child, Preschool , Nevus, Blue/pathology , Nevus of Ota/diagnosis , Nevus of Ota/pathology , Nevus of Ota/therapy , Skin/pathology , Face , Skin Neoplasms/pathologyABSTRACT
Melanoma arising in blue nevus, also known as melanoma ex blue nevus, is a specific form of melanoma whose genetic profile is different to that of other cutaneous melanomas and surprisingly similar to that of uveal melanoma. Although melanoma ex blue nevus can appear de novo, it usually arises in a preexisting blue nevus or dermal melanocytosis. Not all nodular lesions arising in association with blue nevus or dermal melanocytosis are melanomas, however, and because clinical and histologic findings may be insufficient for a definitive diagnosis, additional studies such as comparative genomic hybridization are important. Detection of chromosomal aberrations supports a diagnosis of malignancy. Studies of the BAP1 gene are particularly useful in this setting because loss of expression is indicative of melanoma. We present 3 cases on the spectrum of blue nevus to melanoma ex blue nevus that were studied using molecular biology techniques.
Subject(s)
Melanoma , Nevus, Blue , Skin Neoplasms , Humans , Nevus, Blue/diagnosis , Nevus, Blue/genetics , Nevus, Blue/pathology , Prognosis , Comparative Genomic Hybridization , Melanoma/diagnosis , Melanoma/genetics , Melanoma/pathology , Skin Neoplasms/diagnosis , Skin Neoplasms/genetics , Skin Neoplasms/pathology , Tumor Suppressor Proteins/genetics , Ubiquitin Thiolesterase/geneticsABSTRACT
A limited number of distinct histopathological variants of blue nevus exist, and hamartomatous proliferations involving melanocytic components, dendritic, or otherwise, have also been described. Blue nevus/smooth muscle hamartomas represent a rarely described entity. In this paper, we add two examples of this unusual hamartoma to the existing literature. These additional blue nevus/smooth muscle hamartomas occurred on the left mid-upper back of a 50-year-old woman and the central upper back of a 54-year-old man. Both lesions were clinically atypical pigmented lesions. Histopathologic review of both specimens revealed proliferations of predominantly spindled and pigmented dermal melanocytes with associated smooth muscle hyperplasia, compatible with blue nevus/smooth muscle hamartoma. Both specimens were accompanied by subtle changes suggesting follicular induction, a phenomenon previously described as occurring in a minority of specimens. A brief re-examination of recently diagnosed blue nevus at our institution did not reveal any additional cases in which a subtle smooth muscle component had been missed, suggesting this type of hamartoma is, indeed, exceedingly rare.
Subject(s)
Muscle, Smooth/pathology , Nevus, Blue/pathology , Skin Neoplasms/pathology , Female , Humans , Hyperplasia , Male , Middle AgedABSTRACT
PURPOSE: To describe two patients with blue nevi of the palpebral conjunctiva and to review the existing literature on common and cellular blue nevi of the conjunctiva. METHODS: Report of two cases and literature review. RESULTS: We present two cases of blue nevi in the palpebral conjunctiva: an atypical cellular blue nevus of the left upper eyelid and a common blue nevus around the lacrimal punctum of the left lower eyelid. Both patients underwent full thickness eyelid excision with wide margins. There was no tumor recurrence at 11 and 4 months postoperatively. CONCLUSIONS: Blue nevi are a group of melanocytic tumors that rarely involve the ocular adnexa. They may arise in the palpebral conjunctiva and should be considered in the differential diagnosis of pigmented lesions in this location as they can mimic melanoma.
Subject(s)
Conjunctival Neoplasms , Nevus, Blue , Skin Neoplasms , Conjunctiva/pathology , Conjunctival Neoplasms/diagnosis , Diagnosis, Differential , Humans , Neoplasm Recurrence, Local/pathology , Nevus, Blue/diagnosis , Nevus, Blue/pathology , Nevus, Blue/surgery , Skin Neoplasms/pathology , SyndromeABSTRACT
The cellular blue nevus tumor is a type of dendritic melanocytic nevus that is typically benign and exceedingly rare. The incidence of all blue nevi is about 1%, usually affecting the adult population and appearing on the extremities, sacrococcygeal or gluteal regions. There have only been a handful of case reports cited in the literature where cellular blue nevi present in the head and neck region, usually affecting the scalp and young adult population (7, 8). As such, it is exceedingly rare to encounter a cellular blue nevus tumor in the neck or infiltrating into neck lymph nodes. Here we report a rare case of a cellular blue nevus tumor presenting as a right neck mass in a pediatric 16-year-old patient, shown to invade into the submandibular lymph node and surrounding soft tissue. It is important to be aware of the cellular blue nevus tumor as a differential diagnosis in pediatric neck masses. Histological evaluation is necessary to determine tumor aggression and malignant potential which can guide further treatment in pediatric patients.
Subject(s)
Lymph Nodes/pathology , Mandible , Nevus, Blue/pathology , Skin Neoplasms/pathology , Adolescent , Biomarkers, Tumor/analysis , Diagnosis, Differential , Female , Humans , Lymph Nodes/surgery , MART-1 Antigen/analysis , Nevus, Blue/diagnosis , Nevus, Blue/surgery , SOXE Transcription Factors/analysis , Skin Neoplasms/diagnosis , Skin Neoplasms/surgery , Tomography, X-Ray Computed , Treatment Outcome , gp100 Melanoma Antigen/analysisABSTRACT
OBJECTIVE: To report a rare case of intraoral extensive blue nevus in an elder patient. BACKGROUND: Oral blue nevi is a well-recognised skin melanocytic neoplasm that rarely occurs in the oral cavity and may mimic melanoma in the early stages. METHODS: An incisional biopsy was performed, and the diagnosis was blue nevus. CONCLUSION: Both the clinician and pathologist must be aware of such a presentation to diagnose and treat appropriately.
Subject(s)
Melanoma , Mouth Neoplasms , Nevus, Blue , Skin Neoplasms , Aged , Biopsy , Diagnosis, Differential , Humans , Mouth Neoplasms/diagnosis , Nevus, Blue/diagnosis , Skin Neoplasms/diagnosisABSTRACT
Blue nevus (BN), in all its clinical variants, rarely affects the nail bed. This leads to difficulty in the diagnosis of BN within the nail bed as well as to challenges with regard to its treatment and follow-up management, not solely attributed to the intrinsic difficulty of the anatomical site. We present the first case in the literature of an acquired cellular BN entirely confined within the nail bed, in a female Caucasian patient. We propose diagnostic and therapeutic options based on personal clinical and surgical experience.
Subject(s)
Nevus, Blue , Skin Neoplasms , Female , Humans , Nails , Nevus, Blue/diagnosis , Skin Neoplasms/diagnosisABSTRACT
An atypical cellular blue nevus, a benign mass, may sometimes transform into a malignant melanoma. Here, we report a rare case of melanoma arising in a large congenital vulvar blue nevus. A 28-year-old Chinese woman presented to our hospital with a chief complaint of a vulvar mass that had persisted for 8 years. The patient underwent extensive local excision, followed by reconstructive surgery of the female reproductive tract. The mass was diagnosed as being a vulvar malignant melanoma. Postoperatively, the patient received interferon immunotherapy and recovered without complications. No evidence of recurrence was observed after 32 months of follow-up. Our case thus shows that comprehensive treatment with surgery supplemented by immunotherapy can be effective against a malignant melanoma arising in a vulvar blue nevus.
Subject(s)
Melanoma , Nevus, Blue , Skin Neoplasms , Vulvar Neoplasms , Adult , Female , Humans , Melanoma/surgery , Neoplasm Recurrence, Local , Nevus, Blue/diagnosis , Nevus, Blue/therapy , Skin Neoplasms/therapy , Vulvar Neoplasms/surgeryABSTRACT
A 36-year-old man presented with a subcutaneous nodule on the right upper arm. A small nodule had developed 8 years earlier, and grew in size, accompanied by a tingling sensation and numbness. In addition, he had a bluish irregular patch on the right hand since birth, which crossed from the palm to the dorsal hand. Skin biopsies from the hand showed a heavily pigmented melanocyte proliferation in the dermis with perieccrine, perivascular, and perineural involvement, and a diagnosis of congenital plaque-type blue nevus was made. The tumor on the arm was located closely along the median nerve, and was observed as a large black pedunculated round tumor. Histopathologically, the tumor on the arm consisted of densely packed tissue with nevoid cells without atypia in the larger nodular part, and heavily pigmented spindle and epithelioid melanocytes in the slender stalk area, which was diagnosed as cellular blue nevus with pigmented epithelioid melanocytoma-like pattern. Next-generation sequencing revealed GNAQ mutations in the hand lesion, and in the lesions on the arm. This case suggests that the areas of skin following the same neural distribution of a congenital plaque-type blue nevus on the extremities should be followed up for secondary changes.
Subject(s)
Melanocytes , Nevus, Blue , Skin Neoplasms , Adult , Arm/pathology , Humans , Male , Melanocytes/metabolism , Melanocytes/pathology , Nevus, Blue/metabolism , Nevus, Blue/pathology , Skin/metabolism , Skin/pathology , Skin Neoplasms/metabolism , Skin Neoplasms/pathologyABSTRACT
Melanoma ex blue nevus (MEBN) is a rare, aggressive, and potentially lethal neoplasm. Distinguishing MEBN from an atypical cellular blue nevus can be very challenging. We report a diagnostically difficult case of MEBN with lymph node metastases, in which single nucleotide polymorphism array and fluorescence in situ hybridization were used to arrive at the correct diagnosis. It was also analyzed by the recently-introduced proprietary 23-gene expression signature test. To the best of our knowledge, this is the second reported case of MEBN analyzed by the 23-gene expression signature, which provided a false-negative result. More studies are needed to assess the sensitivity and specificity of this test in various melanocytic proliferations.
Subject(s)
Gene Expression Profiling , Head and Neck Neoplasms/diagnosis , Melanoma/diagnosis , Nevus, Blue/pathology , Skin Neoplasms/diagnosis , Adult , Head and Neck Neoplasms/genetics , Head and Neck Neoplasms/pathology , Humans , Male , Melanoma/genetics , Melanoma/pathology , Nevus, Blue/genetics , Scalp/pathology , Skin Neoplasms/genetics , Skin Neoplasms/pathologyABSTRACT
INTRODUCTION: Ultrasonographic examination is commonly used in an outpatient setting, possibly due to its low cost, low risk for patients and the possibility to obtain real time images. Typically used heads have the frequency ranging from 7.5 to 12 MHz. Higher frequencies ensure higher resolution, yet they are limited by the penetration depth - reaching from several to several tens of millimetres into the skin. High-frequency ultrasonography (HFUS) appears to be a promising method for the detection and differential diagnostics of selected nodular skin lesions. AIM: The study aimed at a comparison of the data obtained by using HFUS, histopathological and dermatoscopic images of selected skin lesions to determine their common features. MATERIAL AND METHODS: Nodular lesions classified as potentially malignant were subjected to clinical, dermatoscopic and high-frequency ultrasonographic examinations. Then the patients were referred for surgical removal with histopathological assessment. RESULTS: A total of 54 nodular lesions were examined, out of which 34 were diagnosed as non-melanoma. The most common lesions were melanocytic naevi dermatofibroma, nodular basal cell carcinoma and pyogenic granuloma. Other examined lesions included blue naevus, seborrheic wart, xanthogranuloma juvenile and Spits naevus. In all lesions except Spitz naevus, HFUS images corresponded at least with dermatoscopic or histopathology images. CONCLUSIONS: HFUS can be used as a supporting diagnostic tool ensuring better pre-operative proceedings. HFUS is a non-invasive, easy and inexpensive screening method for the determination of different skin cancers as it provides valuable information allowing to determine the cutting margins and lesion shape.
ABSTRACT
BACKGROUND: Pigmented epithelioid melanocytoma (PEM) is an uncommon, recently described entity with unknown biologic behavior. There is a high rate of regional metastases, but limited evidence of distant metastases or disease-related death. OBJECTIVE: We sought to report our series of patients given a diagnosis of PEM at our institution and provide mutational analysis of genes commonly implicated in melanoma in 2 cases. METHODS: The pathology database was queried for cases of PEM diagnosed at the University of Rochester. Charts were reviewed for follow-up information. Mutational analysis of melanoma-associated genes was performed on 2 cases. RESULTS: Nine cases of PEM were retrieved in a 10-year retrospective review. Five patients underwent sentinel lymph node biopsy with 3 of 5 having a positive sentinel lymph node. All 9 patients are alive and disease-free with average follow-up of 38.75 months. Two tumors were tested for common melanoma-associated mutations, and were negative, except for a telomerase reverse transcriptase promoter deletion detected in 1 sample. The deletion has not been associated with melanoma, and therefore its biologic significance is unclear. LIMITATIONS: Small sample size, retrospective nature, and single institution experience are limitations. CONCLUSIONS: PEM appears to have an indolent behavior. However, currently the evidence is too limited to provide insight into its true biologic potential.
Subject(s)
Melanoma/secondary , Nevus, Blue/pathology , Skin Neoplasms/pathology , Adolescent , Adult , Child , Child, Preschool , DNA Mutational Analysis , Female , Humans , Lymphatic Metastasis , Male , Melanoma/genetics , Melanoma/surgery , Middle Aged , Neoplasm Staging , Promoter Regions, Genetic , Retrospective Studies , Sentinel Lymph Node Biopsy , Skin Neoplasms/genetics , Skin Neoplasms/surgery , Survival Rate , Telomerase/genetics , Young AdultABSTRACT
Blue nevi are a heterogeneous group of dermal melanocytic proliferations that share a common clinical appearance but remain controversial in their histopathologic and biologic distinction. While common blue nevi and cellular blue nevi are well-defined entities that are classified without significant controversy, the distinction between atypical cellular blue nevi and blue nevus-like melanoma remains diagnostically challenging. We report a case of a 46-year-old female with recurrent blue nevus-like melanoma of the scalp with liver metastases; mutational analysis showed GNA11 Q209L and BAP1 Q393 mutations. To our knowledge, this is the first case of blue nevus-like melanoma with GNA11 and BAP1 mutations. These particular mutations and the predilection for liver metastases in our patient's case underscore a fundamental biological relationship between blue nevi and uveal melanoma and suggest the two entities may prove amenable to similar diagnostic and prognostic testing and targeted therapies.
Subject(s)
GTP-Binding Protein alpha Subunits/genetics , Melanoma/pathology , Nevus, Blue/pathology , Skin Neoplasms/pathology , DNA Mutational Analysis , Female , Humans , Liver Neoplasms/secondary , Melanoma/genetics , Middle Aged , Mutation , Neoplasm Recurrence, Local/genetics , Neoplasm Recurrence, Local/pathology , Nevus, Blue/genetics , Skin Neoplasms/genetics , Tumor Suppressor Proteins/genetics , Ubiquitin Thiolesterase/geneticsABSTRACT
Blue rubber bleb nevus syndrome (BRBNS) involves cutaneous vascular malformation characterized by multiple venous malformations. This commonly affects the skin and gastrointestinal tract. BRBNS is associated with anemia and occasionally involves orthopedic manifestations. A 6-year-old boy was referred to hospital for evaluation of anemia. He presented with a rubber-like soft-tissue mass in the left knee and the right side of the neck, recurrent pain, and fixed flexion contracture of the knee. Blood examination indicated consumption coagulopathy and anemia caused by not only iron-deficiency anemia but also microangiopathy. Endoscopy of the gastrointestinal tract indicated multiple bluish-black sessile venous malformations. Ultrasonography and magnetic resonance imaging of the knee showed intra-articular and intramuscular involvement. Based on these findings, BRBNS with knee joint disorder was diagnosed. With regard to vascular malformations, like other diseases such as inflammatory arthropathy, ultrasonography of the joint may become a new diagnostic approach for evaluating orthopedic manifestations.