Proliferative Nodules Research Articles

Proteomic Mass Spectrometry Imaging for Skin Cancer Diagnosis.

Mass spectrometry imaging can be successfully used for skin cancer diagnosis, particularly for the diagnosis of challenging melanocytic lesions. This method analyzes proteins within benign and malignant melanocytic tumor cells and, based on their differences, which constitute a unique molecular signature of 5 to 20 proteins, can render a diagnosis of benign nevus versus malignant melanoma. Mass spectrometry imaging may assist in the differentiation between metastases and nevi as well as between proliferative nodules in nevi and melanoma arising in a nevus. In the difficult area of atypical Spitzoid neoplasms, mass spectrometry diagnosis can predict clinical outcome better than histopathology.

Paediatric melanoma.

Paediatric melanoma, although rare, is the most common skin cancer in children. Our current knowledge on paediatric melanoma incidence trends is expanding, as several studies have addressed this issue with conflicting results. Known risk factors for paediatric melanoma include family history of melanoma, a previous history of malignancy, large congenital nevi, numerous melanocytic nevi, sunburns, increased UV exposure and a sun-sensitive phenotype. In younger children, melanoma more often presents with atypical features, such as a changing, amelanotic or uniformly coloured, often bleeding lesion, not fulfilling in most cases the conventional ABCDE criteria. The major differential diagnoses are melanocytic nevi, proliferative nodules in congenital nevi and atypical Spitz tumours. Moreover, in the younger age group non-Caucasian children are over-represented, tumours tend to be thicker and lymph nodes are often involved. Despite the frequent diagnosis at an advanced stage, the overall survival is fair in paediatric melanoma. Specific guidelines for management of melanoma in children do not exist, and most often the disease is treated similarly to melanoma in adults.

Clinical course, treatment modalities, and quality of life in patients with congenital melanocytic nevi - data from the German CMN registry.

Congenital melanocytic nevi (CMN) are associated with mental stress as well as medical risks for those affected. The German CMN registry was initiated in 2005. Herein, we present results from an interim analysis focusing on disease course, treatment modalities, and quality of life. One hundred patients enrolled in the registry between 2005 and 2012 were included in this prospective cohort study, and asked to participate in a follow-up survey. In addition, standardized questionnaires were used to collect data on quality of life (dermatology life quality index, DLQI) and perceived stigmatization (perceived stigmatization questionnaire, PSQ; social comfort questionnaire, SCQ). Eighty-three percent of patients (or their parents) provided answers to the survey questions (mean patient age: 11.2 years, median: 6 years; mean follow-up: 4.4 years). Overall, four individuals were diagnosed with melanoma, including two pediatric cases with CNS melanoma, one adult with cutaneous melanoma, and one case which later turned out to be a proliferative nodule. Four children were diagnosed with neurocutaneous melanocytosis, three of whom exhibited neurological symptoms. Eighty-eight percent (73/83) of patients underwent surgery. Seventy-eight percent reported no or only minor impact of the CMN on quality of life. In general, perceived stigmatization and impairment of social well-being were also low. Our results provide an overview of the situation of CMN patients in Germany, Austria, and Switzerland. Three percent of patients developed melanoma; 4% showed CNS involvement.

Reduced H3K27me3 Expression Is Common in Nodular Melanomas of Childhood Associated With Congenital Melanocytic Nevi But Not in Proliferative Nodules.

The formation of a nodule within a congenital melanocytic nevus (CMN) raises concerns about possible melanoma. Most new nodular growths that develop during childhood, however, are benign proliferative nodules (PN); melanoma is very rare. The distinction of melanoma from PN can at times be difficult clinically and histopathologically, requiring ancillary molecular tests for diagnosis. Although the application of molecular methods has revealed new insights into the mutational and genomic landscape of childhood melanomas, little is known about epigenetic events that may drive the growth of a melanoma or PN in a CMN. In this study we compared the expression of H3K27me3, a key regulator in chromatin remodelling-controlled transcription, in PNs and pediatric nodular melanomas arising within medium-sized to large CMN by immunohistochemistry. Significant loss of H3K27me3 expression was seen in 4 of 5 melanomas, but not in any of the 20 PNs. This observation suggests that epigenetic events likely play a role in the pathogenesis of melanoma developing in the dermis or subcutis of CMN. Furthermore, assessing for H3K27me3 expression by immunohistochemistry may be diagnostically useful for problematic cases.

5-Hydroxymethylcytosine Expression in Proliferative Nodules Arising within Congenital Nevi Allows Differentiation from Malignant Melanoma

Differentiation of proliferative nodules in giant congenital nevi from melanoma arising within such nevi is an important diagnostic challenge. DNA methylation is a well-established epigenetic modification already observed in the earliest stages of carcinogenesis, which increases during melanoma progression. The ten-eleven translocation enzymes catalyze the oxidation of 5-methylcytosine to 5-hydroxymethylcytosine (5-hmC), which has recently been reported as an epigenetic hallmark associated with tumor aggressiveness and poor prognosis in a wide variety of cancers. In this study, we analyzed 12 proliferative nodules and 13 melanomas both arising in giant congenital nevi and matched results with a control group including 67 benign and malignant melanocytic lesions. Proliferative nodules displayed high 5-hmC expression levels (90.65%) compared with melanomas with almost complete loss of this marker (7.87%). We showed that low 5-hmC levels in melanomas correlate with downregulation of isocitrate dehydrogenase and ten-eleven translocation families of enzymes implicated in the cytosine methylation cycle. Simultaneously, these enzymes were overexpressed in proliferative nodules leading to strong 5-hmC expression. We emphasize the significance of 5-hmC loss for discrimination of melanomas from benign proliferative nodules arising within giant congenital nevi, and for establishing the correct diagnosis in ambiguous cases when histological and immunohistochemical characteristics are not sufficiently specific.

Hepatocutaneous syndrome in Shih Tzus: 31 cases (1996-2014).

To characterize findings in Shih Tzus with progressive superficial necrolytic dermatitis and degenerative vacuolar hepatopathy consistent with hepatocutaneous syndrome. Retrospective case series. 31 Shih Tzus. Medical records were reviewed to obtain information on signalment, history, treatment, outcome, and results of clinicopathologic testing, abdominal ultrasonography, and histologic examination of skin and liver specimens. A pedigree analysis was performed. There were 16 males and 15 females. Median age at the time of diagnosis was 8 years (range, 5 to 14 years). Common clinical signs included lethargy, inappetence, weight loss, and lameness. Twenty-five dogs had cutaneous lesions consistent with hepatocutaneous syndrome; the remaining 6 initially only had hepatic abnormalities, but 3 of the 6 subsequently developed cutaneous lesions. Common clinicopathologic abnormalities included microcytosis (15/24 [63%] dogs) and high serum alkaline phosphatase activity (24/24 [100%] dogs). Hepatic ultrasonographic findings included a hyperechoic or heteroechoic appearance to the parenchyma with innumerable hypoechoic nodules. Histologic hepatic lesions consisted of degenerative vacuolar (glycogen and lipid) hepatopathy associated with minimally fibrotic to nonfibrotic, noninflammatory, proliferative nodules. Pedigree analysis confirmed a common ancestry in 12 of 18 dogs. Median survival time was 3 months (range, 1 to 36 months). Results suggested that HCS may have a heritable component in Shih Tzus, although the condition may also be identified in Shih Tzus without affected relatives. Clinical, clinicopathologic, ultrasonographic, and histologic abnormalities in affected Shih Tzus were similar to those previously reported for dogs of other breeds with HCS.

Paediatric melanoma

Cutaneous melanoma occurs only rarely in children under 10 years of age. Mimics of melanoma, including Spitz naevi and proliferative nodules in congenital melanocytic naevi are much more frequent in this age group. Melanoma arising in congenital melanocytic naevus is uncommon, but can show aggressive behaviour. Although spitzoid lesions constitute the majority of 'diagnostically challenging' cases, they are an uncommon cause of mortality in this age group. Among lesions with undoubted metastatic potential, there are biologically distinct tumours which differ significantly in behaviour from the common types of melanoma seen in adults. In patients over 10 years of age and increasingly into the late adolescent years, melanoma is a relatively common neoplasm. Just as in adult patients, care should be taken to exclude melanoma mimics. Particular care is warranted in this older age group in the assessment of lesions with spitzoid morphology as there is significant potential for both over-and under-diagnosis.

The neural crest lineage as a driver of disease heterogeneity in Tuberous Sclerosis Complex and Lymphangioleiomyomatosis

Lymphangioleiomyomatosis (LAM) is a rare neoplastic disease, best characterized by the formation of proliferative nodules that express smooth muscle and melanocytic antigens within the lung parenchyma, leading to progressive destruction of lung tissue and function. The pathological basis of LAM is associated with Tuberous Sclerosis Complex (TSC), a multi-system disorder marked by low-grade tumors in the brain, kidneys, heart, eyes, lung and skin, arising from inherited or spontaneous germ-line mutations in either of the TSC1 or TSC2 genes. LAM can develop either in a patient with TSC (TSC-LAM) or spontaneously (S-LAM), and it is clear that the majority of LAM lesions of both forms are characterized by an inactivating mutation in either TSC1 or TSC2, as in TSC. Despite this genetic commonality, there is considerable heterogeneity in the tumor spectrum of TSC and LAM patients, the basis for which is currently unknown. There is extensive clinical evidence to suggest that the cell of origin for LAM, as well as many of the TSC-associated tumors, is a neural crest cell, a highly migratory cell type with extensive multi-lineage potential. Here we explore the hypothesis that the types of tumors that develop and the tissues that are affected in TSC and LAM are dictated by the developmental timing of TSC gene mutations, which determines the identities of the affected cell types and the size of downstream populations that acquire a mutation. We further discuss the evidence to support a neural crest origin for LAM and TSC tumors, and propose approaches for generating humanized models of TSC and LAM that will allow cell of origin theories to be experimentally tested. Identifying the cell of origin and developing appropriate humanized models is necessary to truly understand LAM and TSC pathology and to establish effective and long-lasting therapeutic approaches for these patients.

BAP1 and BRAFV600E expression in benign and malignant melanocytic proliferations.

BAP1 (BRCA1-associated protein 1) is a tumor suppressor gene whose mutations have recently been reported to increase susceptibility for the development of uveal melanoma, cutaneous atypical and epithelioid melanocytic lesions, clear cell renal cell carcinoma, and other tumors. Screening for BAP1 mutation/loss/inactivation and BRAFV600E mutation can be done by immunohistochemistry. We investigated BAP1 and BRAFV600E expression in 193 sporadic melanocytic lesions (11 dermal nevi, 20 congenital nevi, 40 primary and nondesmoplastic melanomas, 40 desmoplastic melanomas, 23 metastatic melanomas, 17 Spitz nevi, 19 atypical Spitz nevi, 8 atypical Spitz tumors, 14 proliferative nodules arising in congenital nevi, 1 nevus during pregnancy) and 30 melanocytic lesions from 3 patients with family history of uveal melanoma and BAP1 germline mutation. Most sporadic melanocytic lesions exhibited positive BAP1 nuclear staining, except for 1 proliferative nodule arising in congenital nevus, 1 desmoplastic, 1 nevoid, and 2 metastatic melanomas. BRAFV600E positivity was demonstrated in 80% of dermal, 5% of congenital, 6% of Spitz, and 5.5% of atypical Spitz nevi; 29% of proliferative nodules arising in congenital nevi; and 24% of primary and nondesmoplastic and 35% of metastatic melanomas. Combined BAP1 loss and BRAFV600E staining was seen in 67% of BAP1 tumor syndrome-associated lesions and in none of the sporadic melanocytic proliferations including Spitz and atypical Spitz nevi and atypical Spitz tumors, with the exception of 1 primary melanoma. The combined BAP1-BRAFV600E+ immunoprofile appears to be a constant feature of BAP1 tumor syndrome-associated melanocytic lesions, and the designation of Spitz nevi or variants thereof appears to be inaccurate for this group of lesions.

Proliferative nodules in congenital melanocytic nevi: a clinicopathological analysis of eight cases

To study the clinicopathologic features, differential diagnosis and prognosis of proliferative nodules(PNs) in congenital melanocytic nevi(CMN). Histopathologic evaluation and immunohistochemical study by EnVision method were carried out in 8 cases of PNs in CMN. The clinical information and follow-up data were analyzed. The age of patients ranged from 1 to 54 years (mean 27.6 years). Tumors were located on face (3 cases), on back (2 cases), upper extremities (2 cases) and lower extremities(1 case). Microscopically, PNs with expansile growth were observed in 8 cases of CMN. Melanocytes in PNs show variable pleomorphism with a mitotic activity of 0 to 4 per 10 high power fields. Blending of cells with adjacent CMN was noted in 6 cases. According to the morphology of melanocytes in PNs, it was classified into different types including large oval melanocytes (4 cases), small melanocytes (2 cases) and Spitz-nevus-like forms (2 cases). Immunohistochemically, melanocytes in PNs were consistent with those in adjacent CMN. They were diffusely positive for S-100 protein, but were either negative or focally positive for HMB45. Less than 5% of melanocytes were positive for Ki-67 in 8 cases of PN. Follow-up was available in all cases, ranging from 9 to 82 months. Seven patients with excision of single PN in CMN were alive with no evidence of disease, while 1 patient with multiple PNs in CMN was stable with disease after 62 months follow-up. PN is a rare melanocytic lesion arising in CMN. Recognition of its specific histologic features can help to avoid being misdiagnosed as melanoma. Long term follow-up should be recommended in patients with PNs, especially in those with atypical histologic features. Further investigation is needed to elucidate its clinical behavior.

Core concepts in congenital melanocytic nevi and infantile hemangiomas

Congenital melanocytic nevi (CMN) and infantile hemangiomas are commonly encountered in newborns and may present diagnostic and therapeutic dilemmas for medical practitioners. Herein, we review and discuss these two important clinical entities and focus on core issues and recent advances. Melanoma risk for patients with CMN is greatest in infants with large CMN located on the trunk, CMN greater than 40 cm, and multiple satellite nevi. Recent histological and molecular findings have been described to assist in differentiating benign proliferative nodules arising in CMN from melanoma. Multiple CMN and associated neurological lesions have recently been shown to be due to a single postzygotic mutation in NRAS [neuroblastoma RAS viral (v-ras) oncogene homolog]. Over the last several years, numerous advancements have occurred in redefining the clinical course of infantile hemangiomas, describing clinical syndromes associated with infantile hemangiomas and treating complicated infantile hemangiomas. The nonselective β-blocker propranolol has become first-line therapy for the treatment of complicated infantile hemangiomas. Topical timolol shows promise for the treatment of certain types of infantile hemangiomas. Although most CMN and infantile hemangiomas do not require active intervention, understanding which lesions may impact the overall health of the infant assists in early intervention. This article touches on core concepts in the clinical evaluation and treatment of CMN and infantile hemangioma.

Giant Congenital Melanocytic Nevus with Proliferative Nodules Mimicking a Congenital Malignant Melanoma

Dear Editor: The malignant transformation of a giant congenital nevus (GCN) is extremely rare, and when it is discovered, the transformation may have already occurred during childhood. Benign proliferative nodules (PNs) in GCN may clinically and histologically mimic a malignant (MM), but clinically, PNs usually present at birth with multiple nodules, which is in contrast to MMs, and histologically, most patients with PNs do not present with the characteristics that are associated with malignancy, including mitotic activity, nuclear pleomorphism, and pagetoid spreading. Furthermore, even though some cases might display these features, they soon disappear1. A one-day-old female child presented with GCN on her lower abdomen, genitalia, anus, and legs. Prenatal ultrasonography revealed an imperforate anus, but no genital abnormalities. Dark brown plaques and some PNs that covered the involved areas were seen during a physical examination (Fig. 1). Satellite nevi were encountered on her scalp, axillae, and ankles. A diagnostic biopsy on a PN was performed, and the histological examination presented a proliferative dermal nodule in a GCN (Fig. 2A). The nevus cells had formed nests in the dermo-epidermal junction and the upper dermis (Fig. 2A, B). They were homogenous without nuclear atypia, pleomorphisms, mitoses, or pagetoid spreading into the epidermis. The melanocytic cells in the dermal nodule showed more dense cellularity than in the background lesion (Fig. 2C), and these cells were more pigmented and larger, and most of them were epithelioid cells that showed little pleomorphism and low-grade cytologic atypia. The features of necrosis were not found. All of these histological features was consistent with a benign PN within a GCN. Immunohistochemical analysis showed that the PN was positive for HMB45 (Fig. 2D), Melan A (Fig. 2E), and SOX-10 (Fig. 2F), which detect melanocytic tumors and Ki-67 protein of less than 2% (Fig. 2G). The patient was transferred to the plastic surgery department and she underwent a staged excision. Fig. 1 A giant congenital nevus with proliferative nodules on lower abdomen, genitalia, anus and lower legs. Fig. 2 (A) Histopathology of the proliferative nodule showed a proliferative dermal nodule in a giant congenital nevus (H&E, ×40). (B) Congenital nevus cells formed nests at the dermo-epidermal junction and upper dermis (H&E, ×200). ... Congenital nevi occur in 1% of newborn infants. Some authors have stated that GCN can be distinguished histologically from acquired nevi by the presence of nevoid cells in the lower two-thirds of the dermis1. Other authors have reported that the nevus cells subsequently migrate deeper into the dermis2. GCN has a 2%~42% risk of malignant transformation, and is associated with a 6%~14% lifetime risk of developing melanoma3. True congenital melanomas are very rare and they are supposed to develop secondary to the transplacental spread of maternal melanomas, arise de novo in uterus, present as prenatal growths on congenital nevi, or arise from neurocutaneous melanosis. A PN within a congenital nevus is also uncommon. Compared with congenital nevus cells, PN cells are larger and more pigmented, they have large nucleoli and a storiform pattern, and they can form nests. These cells have been called melanoma stimulant cells4. The etiology of them is unknown, and they may be a monoclonal proliferation of melanocytic cells. PNs within GCN grow rapidly, show satellitosis5, and they often bring up diagnostic difficulty. In a study of the cells in PNs in GCN, the cells showed high malignancy, but they did not present the typical antigens expressed in MMs, and their subsequent behavior was benign5. But, because the possibility of malignant transformation of this cells is unclear, surgical procedure is recommended to exclude congenital melanoma. We presented the current case to underline the development of benign PN within GCN and to suggest its differential diagnosis from congenital MM.

先天性巨大色素性母斑に生じたproliferative noduleの1例

22歳，女性。生下時より左肩から背部にかけて広範な色素性母斑あり。左肩の色素斑の中に小学生の頃に皮下結節出現。徐々に増大してきたため紹介受診。現症：左肩の色素斑の中に1.5 cm大の皮下結節あり。局所麻酔下に皮下結節を摘出した。病理組織学的に結節を作る細胞と周囲の母斑細胞との間に移行像がみられること，細胞の異型性は高度ではないこと，分裂像は少なく，異常核分裂像がみられないこと，壊死像がみられないこと，Ki－67陽性細胞が7％と高くないことが観察された。以上より先天性巨大色素性母斑に生じたproliferative noduleと診断した。術後1年6ヵ月経つが，再発，転移は認められていない。

Congenital Malignant Melanoma

Although rare, congenital malignant melanoma (CMM) should be considered in the differential diagnosis of congenital skin lesions. We report a case of CMM in a 4-month-old infant presenting with an enlarging scalp mass, initially thought to be a hemangioma. Incisional biopsy of the lesion showed a compound congenital nevus with atypical cells suggestive of a proliferative nodule versus malignancy on histopathology. Subsequent excisional biopsy revealed malignant melanoma, and further workup confirmed extensive disease with distant metastases. Cytogenetic analysis of both the tumor sites showed highly abnormal karyotypes including pseudotetraploidy, telomere associations, and evidence of gene amplification, all consistent with malignancy. Fluorescence in situ hybridization demonstrated amplification of the MYC gene, with no copy number changes in CDKN2A (INK4/ARF), PTEN, or Cyclin D1. Our report details the cytogenetic and molecular studies of CMM, which provide insight into the biologic behavior of the lesions and may confirm diagnosis when histopathology is not determinant.

A neonatal case of proliferative nodules in a giant congenital melanocytic nevus with histological evaluation

International Journal of DermatologyVolume 53, Issue 4 p. e252-e253 Correspondence A neonatal case of proliferative nodules in a giant congenital melanocytic nevus with histological evaluation Kio Park MD, Kio Park MD [email protected] Department of Dermatology, Nara Medical University, Nara, JapanSearch for more papers by this authorTakaya Fukumoto MD, PhD, Takaya Fukumoto MD, PhD Department of Dermatology, Nara Medical University, Nara, JapanSearch for more papers by this authorChinatsu Kuki MD, Chinatsu Kuki MD Department of Dermatology, Nara Medical University, Nara, JapanSearch for more papers by this authorHideo Asada MD, PhD, Hideo Asada MD, PhD Department of Dermatology, Nara Medical University, Nara, JapanSearch for more papers by this authorMasamitsu Kuwahara MD, PhD, Masamitsu Kuwahara MD, PhD Department of Dermatology, Division of Plastic Surgery, Nara Medical University, Nara, JapanSearch for more papers by this authorTakahiko Kasai MD, PhD, Takahiko Kasai MD, PhD Department of Diagnostic Pathology, Nara Medical University, Nara, JapanSearch for more papers by this author Kio Park MD, Kio Park MD [email protected] Department of Dermatology, Nara Medical University, Nara, JapanSearch for more papers by this authorTakaya Fukumoto MD, PhD, Takaya Fukumoto MD, PhD Department of Dermatology, Nara Medical University, Nara, JapanSearch for more papers by this authorChinatsu Kuki MD, Chinatsu Kuki MD Department of Dermatology, Nara Medical University, Nara, JapanSearch for more papers by this authorHideo Asada MD, PhD, Hideo Asada MD, PhD Department of Dermatology, Nara Medical University, Nara, JapanSearch for more papers by this authorMasamitsu Kuwahara MD, PhD, Masamitsu Kuwahara MD, PhD Department of Dermatology, Division of Plastic Surgery, Nara Medical University, Nara, JapanSearch for more papers by this authorTakahiko Kasai MD, PhD, Takahiko Kasai MD, PhD Department of Diagnostic Pathology, Nara Medical University, Nara, JapanSearch for more papers by this author First published: 24 July 2013 https://doi.org/10.1111/ijd.12282Citations: 3Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL No abstract is available for this article.Citing Literature Volume53, Issue4April 2014Pages e252-e253 RelatedInformation

Rosette-like structures in the spectrum of spitzoid tumors

Spitz nevi demonstrate a diverse spectrum of morphologies. Recently, there have been two reported examples of Spitz nevi with rosette-like structures similar to Homer-Wright rosettes. Rosettes have also been described in melanomas and in a proliferative nodule arising in a congenital nevus. A retrospective review of 104 cases of Spitz nevi and variants (n = 51), pigmented spindle cell nevi (n = 26), combined melanocytic nevi with features of Spitz (n = 8), atypical Spitz tumor (AST, n = 9), and spitzoid melanoma (n = 10). Rosette-like structures were present in 3 of the 104 cases (2.9%), including a compound Spitz nevus, a desmoplastic Spitz nevus, and an AST. All three cases demonstrated several foci of small nests of epithelioid cells with peripherally palisaded nuclei arranged around a central area of fibrillar eosinophilic cytoplasm. Immunohistochemical staining of the three spitzoid lesions demonstrated that the rosette-like structures express S100 protein, Melan-A, and neuron specific enolase (NSE) and lacked expression of neurofilament, glial fibrillary acidic protein and synaptophysin. While uncommon, rosette-like structures can occur as a focal feature in Spitz nevi and AST. Rosette-like structures may represent a normal morphologic finding in Spitz nevi, and awareness of them may prevent misdiagnosis as a neural tumor or melanoma.

THU0436 Tuberculosis in Rheumatoid Arthritis - A Retrospective Clinicopathologic Study of 234 Autopsy Patients

BackgroundTuberculosis (Tb) is one of the most important diseases accompanying rheumatoid arthritis (RA) (1). The risk of miliary dissemination in post-primary tuberculosis (mTb) is high in rheumatoid arthritis (RA), because...

Mitotically Active Proliferative Nodule Arising in a Giant Congenital Melanocytic Nevus

Proliferative (cellular) nodules (PN) which mimic malignant melanoma clinically and histologically are described in congenital melanocytic nevi (CMN) and may pose significant diagnostic challenges. We report the case of a 10-day-old male with a giant congenital nevus involving the neck, upper chest, back, and left shoulder containing several nodular lesions, some crusted. Biopsy of a nodule revealed densely packed nevus cells with hyperchromatic round to oval and occasionally irregularly shaped nuclei. There was no necrosis or pushing border, and the nodule blended with the adjacent nevus; however, the lesion demonstrated a significant number of mitoses (27 per mm2) and a 60% labeling index with Ki-67. Further analysis by fluorescence in situ hybridization (FISH) with a 4-color probe set targeting 6p25, 6q23, 11q13, and centromere 6 revealed increased chromosomal copy numbers of all 4 probes, which was interpreted as evidence of polyploidy. In addition, analysis of DNA copy number changes using a single nucleotide polymorphism microarray (Affymetrix, Santa Clara, CA) showed no chromosomal aberrations. The diagnosis of PN in a giant congenital nevus was eventually rendered. At 13-month follow-up, the nodules showed no evidence of growth. Our case illustrates that PNs in the neonatal period might demonstrate extreme mitotic activity. This feature is worrisome when encountered in melanocytic lesions; however, it should not trigger by itself a diagnosis of melanoma in the absence of other histologic criteria of malignancy. In addition, we document polyploidy by FISH in PN, which can potentially be misinterpreted as a FISH-positive result.

Proliferative nodules of undifferentiated spindle cells arising in a large congenital melanocytic naevus

Proliferative nodules (PN) are benign lesions that arise in large congenital melanocytic naevi (LCMN). Clinically and histologically they can be difficult to differentiate from malignancies, which are also associated with LCMN. The PN in this case consisted of undifferentiated spindle cells and exhibited unusual histological features including negative stains for melanocytic markers (S100, HMB45 and MelA), negative stain for c-Kit, high mitotic index and unusual morphology of the lesional cells. As a result, a firm histological classification could not be made, which posed a challenge for the clinical management.

Giant Congenital Melanocytic Naevus with Proliferative Nodules Mimicking Congenital Malignant Melanoma: A Case Report and Review of the Literature of Congenital Melanoma

Congenital malignant melanoma (CMM) is a rare condition that is defined as malignant melanoma recognized at birth. CMM may develop in utero in one of three ways: (1) transmission by metastasis through the placenta from a mother with melanoma; (2) primary melanoma arising within a giant congenital melanocytic naevus (GCMN); (3) primary de novo cutaneous CMM arising in utero. CMM can be confused clinically and histologically with benign proliferative melanocytic lesions such as giant congenital nevi. We describe the case of a patient presenting a GCMN with proliferative nodules, clinically and dermoscopically resembling a CMM, demonstrating the importance of caution in making a diagnosis of MM and highlighting the possibility that benign lesions as GCMN can mimic a malignant melanoma in this age group.