A rare case of cutaneous granular cell tumor with unusual Melan-A expression in a child.

Granular cell tumors (GCTs) are rare, indolent neoplasms classically characterized by eosinophilic granular cytoplasm, infiltrations of polygonal cells in the collagenous stroma, and pustulo-ovoid bodies of Milian. We describe a case of a 10-year-old female presenting with a GCT of the upper arm, remarkable for positive Melan-A expression without additional melanocytic features. The differentiation between granular cells versus melanocytic neoplasms carries significant implications for clinical management, and such diagnoses should be considered carefully in the setting of unusual immunophenotypes.

Cross-Activation of Regulatory T Cells by Self Antigens Limits Self-Reactive and Activated CD8+ T Cell Responses.

The interaction between regulatory T (Treg) cells and self-reactive T cells is a crucial mechanism for maintaining immune tolerance. In this study, we investigated the cross-activation of Treg cells by self-antigens and its impact on self-reactive CD8+ T cell responses, with a focus on the P53 signaling pathway. We discovered that major histocompatibility complex (MHC) I-restricted self-peptides not only activated CD8+ T cells but also induced the delayed proliferation of Treg cells. Following HLA-A*0201-restricted Melan-A-specific (pMelan) CD8+ T cells, we observed the direct expansion of Treg cells and concurrent suppression of pMelan+CD8+ T cell proliferation upon stimulation with Melan-A peptide. Transcriptome analysis revealed no significant alterations in specific signaling pathways in pMelan+CD8+ T cells that were co-cultured with activated Treg cells. However, there was a noticeable upregulation of genes involved in P53 accumulation, a critical regulator of cell survival and apoptosis. Consistent with such observation, the blockade of P53 induced a continuous proliferation of pMelan+CD8+ T cells. The concurrent stimulation of Treg cells through self-reactive TCRs by self-antigens provides insights into the immune system's ability to control activated self-reactive CD8+ T cells as part of peripheral tolerance, highlighting the intricate interplay between Treg cells and CD8+ T cells and implicating therapeutic interventions in autoimmune diseases and cancer immunotherapy.

Inhibitory Effects of Polyphenol- and Flavonoid-Enriched Rice Seed Extract on Melanogenesis in Melan-a Cells via MAPK Signaling-Mediated MITF Downregulation.

Melanin production is an important process that prevents the host skin from harmful ultraviolet radiation; however, an overproduction of melanin results in skin diseases. In the present study, we determined the antioxidative and anti-melanogenic activities of polyphenol- and flavonoid-enriched rice seed extracts in melan-a cells. The polyphenol and flavonoid content of Hopum (HP) and Sebok (SB) rice seed extracts was measured. The antioxidant capacity was determined using the ABTS radical scavenging method. SB contained high amounts of polyphenols and flavonoids, which significantly increased antioxidative activity compared with HP. Various concentrations of these extracts were evaluated in a cytotoxicity using melan-a cells. At 100 µg/mL, there was no significant difference for all treatments compared with untreated cells. Therefore, 100 µg/mL was selected as a concentration for the further experiments. SB significantly suppressed the phosphorylation/activation of p-38 MAPK, increased the expression of phosphorylated ERK 1/2 and Akt, and downregulated the microphthalmia-associated transcription factor (MITF). This resulted in decreased levels of tyrosinase and tyrosinase-related protein-1 and -2. These results indicate the potential of polyphenol- and flavonoid-enriched rice seed as a treatment for hyperpigmentation.

Canine melanocytes: Immunohistochemical expression of melanocytic markers in different somatic areas.

BACKGROUND: Melanoblasts originate in the neural crest from where they migrate to peripheral tissues and differentiate into melanocytes. Alteration during melanocyte development and life can cause different diseases, ranging from pigmentary disorders and decreased visual and auditory functions, to tumours such as melanoma. Location and phenotypical features of melanocytes have been characterised in different species, yet data on dogs are lacking. OBJECTIVE: This study investigates the expression of melanocytic markers Melan A, PNL2, TRP1, TRP2, SOX-10 and MITF in melanocytes of selected cutaneous and mucosal surfaces of dogs. ANIMALS: At necropsy, samples from five dogs were harvested from oral mucosa, mucocutaneous junction, eyelid, nose and haired skin (abdomen, back, pinna, head). MATERIALS AND METHODS: Immunohistochemical and immunofluorescence analyses were performed to assess marker expression. RESULTS: Results showed variable expression of melanocytic markers in different anatomical sites, particularly within epidermis of haired skin and dermal melanocytes. Melan A and SOX-10 were the most specific and sensitive melanocytic markers. PNL2 was less sensitive, while TRP1 and TRP2 were seldomly expressed by intraepidermal melanocytes in haired skin. MITF had a good sensitivity, yet the expression often was weak. CONCLUSIONS AND CLINICAL RELEVANCE: Our results indicate a variable expression of melanocytic markers in different sites, suggesting the presence of subpopulations of melanocytes. These preliminary results pave the way to understanding the pathogenetic mechanisms involved in degenerative melanocytic disorders and melanoma. Furthermore, the possible different expression of melanocyte markers in different anatomical sites could influence their sensitivity and specificity when used for diagnostic purposes.

Establishment and Characterisation of Human Clear Cell Sarcoma and Malignant Melanoma Cell Lines.

BACKGROUND/AIM: Clear cell sarcoma of soft tissue (CCSST) and conventional malignant melanoma (MM) are rare and aggressive tumours with similarities in morphology and the expression of melanocytic markers. MATERIALS AND METHODS: We established two CCSST cell lines (FU-CCSST-1 and FU-CCSST-2) from soft tissues of the patella and supraclavicular. A MM cell line (FU-MM-1) was established from lymph node metastases of subungual malignant melanoma. RESULTS: FU-CCSST-2 cells were transplantable to immunodeficient mice. Immunohistochemical studies demonstrated tumour cells were negative for cytokeratin AE1/AE3 and positive for S100 protein, HMB45, Melan-A, CD146 and SOX10 in all specimens. FU-CCSST-1 and FU-CCSST-2 harboured t(12;22)(q13;q12) translocations with expression of the EWSR1/ATF1 fusion gene. FU-MM-1 demonstrated loss of the short arm of chromosome 9 and harboured wild-type BRAF (codon 469 and 600) and NRAS (codon 12, 13 and 61). CONCLUSION: We report the establishment and characterisation of CCSST and MM cell lines that may have utility in the study of pathogenic mechanisms and development of novel therapeutic reagents.

Malignant gastrointestinal neuroectodermal tumor: A case-based review of literature.

Malignant gastrointestinal (GI) neuroectodermal tumor is an extremely rare entity that was first described by Zambrano et al. in 2003 as "clear cell sarcoma (CCS)-like tumor of the GI tract." It shares some of the histopathological features of CCS but lacks the immunohistochemical (IHC) reactivity for melanocytic markers. Most mesenchymal neoplasms of the GI tract belong to the category of GI stromal tumors and are characterized by the IHC expression of c-KIT. In cases, without detectable KIT receptor expression, several differential diagnoses have to be taken into consideration. In this article, we describe such a case and present a review of all the reported cases till date. We also present the current available knowledge on its pathology and molecular genetics along with the limitations in its diagnosis. Here, we report a case of a 32-year-old man with a tumor of the small bowel composed of polygonal tumor cells arranged in solid nests, alveolar pattern, and pseudopapillary and admixed with numerous osteoclast-like multinucleated giant cells. Immunohistochemically, the tumor cells strongly expressed S-100 protein only. HMB-45, melan-A, CD117, cytokeratin, desmin, smooth muscle actin, and CD-34 were absent. Ki-67 index was 15%. The diagnosis was further confirmed by fluorescence in situ hybridization (FISH) demonstrating the presence of EWSR1 (22q12) translocation. A final diagnosis of malignant gastroneuroectodermal tumor was rendered. The patient is disease-free for 20 months of postsurgery. The diagnosis of this entity should be considered in the presence of S-100-positivity and multinucleated osteoclastic giant cells and the absence of melanocytic differentiation in a tumor arising from GI tract. Further confirmation can be done by performing FISH analysis.

Early disappearance of tumor antigen-reactive T cells from peripheral blood correlates with superior clinical outcomes in melanoma under anti-PD-1 therapy.

BACKGROUND: Anti-programmed cell death protein 1 (PD-1) antibodies are now routinely administered for metastatic melanoma and for increasing numbers of other cancers, but still only a fraction of patients respond. Better understanding of the modes of action and predictive biomarkers for clinical outcome is urgently required. Cancer rejection is mostly T cell-mediated. We previously showed that the presence of NY-ESO-1-reactive and/or Melan-A-reactive T cells in the blood correlated with prolonged overall survival (OS) of patients with melanoma with a heterogeneous treatment background. Here, we investigated whether such reactive T cells can also be informative for clinical outcomes in metastatic melanoma under PD-1 immune-checkpoint blockade (ICB). METHODS: Peripheral blood T cell stimulation by NY-ESO-1 and Melan-A overlapping peptide libraries was assessed before and during ICB in two independent cohorts of a total of 111 patients with stage IV melanoma. In certain cases, tumor-infiltrating lymphocytes could also be assessed for such responses. These were characterized using intracellular cytokine staining for interferon gamma (IFN-γ), tumor negrosis factor (TNF) and CD107a. Digital pathology analysis was performed to quantify NY-ESO-1 and Melan-A expression by tumors. Endpoints were OS and progression-free survival (PFS). RESULTS: The initial presence in the circulation of NY-ESO-1- or Melan-A-reactive T cells which became no longer detectable during ICB correlated with validated, prolonged PFS (HR:0.1; p>0.0001) and OS (HR:0.2; p=0.021). An evaluation of melanoma tissue from selected cases suggested a correlation between tumor-resident NY-ESO-1- and Melan-A-reactive T cells and disease control, supporting the notion of a therapy-associated sequestration of cells from the periphery to the tumor predominantly in those patients benefitting from ICB. CONCLUSIONS: Our findings suggest a PD-1 blockade-dependent infiltration of melanoma-reactive T cells from the periphery into the tumor and imply that this seminally contributes to effective treatment.

Randomized phase II trial of lymphodepletion plus adoptive cell transfer of tumor-infiltrating lymphocytes, with or without dendritic cell vaccination, in patients with metastatic melanoma.

BACKGROUND: The adoptive transfer of tumor-infiltrating lymphocytes (TIL) has demonstrated robust efficacy in metastatic melanoma patients. Tumor antigen-loaded dendritic cells (DCs) are believed to optimally activate antigen-specific T lymphocytes. We hypothesized that the combined transfer of TIL, containing a melanoma antigen recognized by T cells 1 (MART-1) specific population, with MART-1-pulsed DC will result in enhanced proliferation and prolonged survival of transferred MART-1 specific T cells in vivo ultimately leading to improved clinical responses. DESIGN: We tested the combination of TIL and DC in a phase II clinical trial of patients with advanced stage IV melanoma. HLA-A0201 patients whose early TIL cultures demonstrated reactivity to MART-1 peptide were randomly assigned to receive TIL alone or TIL +DC pulsed with MART-1 peptide. The primary endpoint was to evaluate the persistence of MART-1 TIL in the two arms. Secondary endpoints were to evaluate clinical response and survival. RESULTS: Ten patients were given TIL alone while eight patients received TIL+DC vaccine. Infused MART-1 reactive CD8+ TIL were tracked in the blood over time by flow cytometry and results show good persistence in both arms, with no difference in the persistence of MART-1 between the two arms. The objective response rate was 30% (3/10) in the TIL arm and 50% (4/8) in the TIL+DC arm. All treatments were well tolerated. CONCLUSIONS: The combination of TIL +DC showed no difference in the persistence of MART-1 TIL compared with TIL therapy alone. Although more patients showed a clinical response to TIL+DC therapy, this study was not powered to resolve differences between groups. TRIAL REGISTRATION NUMBER: NCT00338377.

Dermal melanocytic tumor with CRTC1-TRIM11 fusion: Report of two additional cases with review of the literature of an emerging entity.

"Cutaneous melanocytic tumor with CRTC1-TRIM11 fusion" (CMTCT) is a newly described, potentially novel entity that typically presents as a dermal nodule on the head and neck, extremities, and trunk of adults. Histopathologically, it is reported as a nodular or multinodular tumor composed of epithelioid and spindle cells that are variably immunoreactive for S100-protein, SOX10, and MITF along with more specific melanocytic markers such as MelanA and HMB45. With only 11 cases reported in the English literature so far, the neoplasm appears to behave in a relatively indolent fashion. Nevertheless, in one case, local recurrence and synchronous distant metastasis were evident after 13 years. Additional cases with longer follow-up are essential to determine the neoplasm's biologic behavior with more accuracy. Herein, two cases of CMTCT, one arising on the lower back of a 65-year-old female and the other on the arm of a 33-year-old female in addition to a comprehensive literature review are reported.

Pure and Mixed Desmoplastic Melanomas: A Retrospective Clinicopathologic Comparison of 33 Cases.

BACKGROUND: Pure and mixed desmoplastic melanomas (DMs) may have different natural histories and behaviors. METHODS: We conducted a retrospective review of patients diagnosed with DM at our institution between January 1997 and April 2019. A total of 33 unique DMs were identified and subsequently analyzed based on the histologic type (pure vs. mixed). RESULTS: The majority (57.6%) of our cases were classified as pure histology. Patients with pure DMs were more likely to be men (P = 0.035) and be older than 65 years (P = 0.019) compared with patients with mixed DMs. Patients with mixed DM were more likely to have mitoses present (P = 0.001) compared with patients with pure DM. There were no differences in ulceration, perineural invasion, vascular invasion, or survival between patients with pure and mixed histologic subtypes. In addition, no differences in sentinel lymph node biopsy, radiation, or chemotherapy were noted between the 2 histologic subtypes. Immunohistochemistry showed that 27.3% of the pure DMs stained with Melan-A and HMB45 were positive for these immunomarkers. CONCLUSIONS: Pure and mixed variants of DM were found to have similar clinicopathologic characteristics. Patients with the mixed histologic subtype were more likely to have mitoses, but no difference in the therapeutic management or patient survival was seen between the 2 subtypes.

In-vivo imaging for assessing tumor growth in mouse models of ocular melanoma.

Uveal melanoma (UM) and conjunctival melanoma (CM) are ocular malignancies that give rise to life-threatening metastases. Although local disease can often be treated successfully, it is often associated with significant vision impairment and treatments are often not effective against metastatic disease. Novel treatment modalities that preserve vision may enable elimination of small tumors and may prevent subsequent metastatic spread. Very few mouse models of metastatic CM and UM are available for research and for development of novel therapies. One of the challenges is to follow tumor growth in-vivo and to determine the right size for treatment, mainly of the posterior, choroidal melanoma. Hence, the purpose of this study was to establish a simple, noninvasive imaging tool that will simplify visualization and tumor follow-up in mouse models of CM and UM. Tumors were induced by inoculation of murine B16LS9 cells into the sub-conjunctival or the choroidal space of a C57BL/6 mouse eye under a surgical microscope. Five to ten days following injection, tumor size was assessed by Phoenix MicronIV™ image-guided Optical Coherence Tomography (OCT) imaging, which included a real-time camera view and OCT scan of the conjunctiva and the retina. In addition, tumor size was evaluated by ultrasound and histopathological examination of eye sections. Tumor growth was observed 5-9 days following sub-conjunctival or sub-retinal injection of seven-thousand or seventy-thousand cells, respectively. A clear tumor mass was detected at these regions using the MicronIV™ imaging system camera and OCT scans. Histology of eye sections confirmed the presence of tumor tissue. OCT allowed an accurate measurement of tumor size in the UM model and a qualitative assessment of tumor size in the CM model. Moreover, OCT enabled assessing the success rate of the choroidal tumor induction and importantly, predicted final tumor size already on the day of cell inoculation. In conclusion, by using a simple, non-invasive imaging tool, we were able to follow intraocular tumor growth of both CM and UM, and to define, already at the time of cell inoculation, a grading scale to evaluate tumor size. This tool may be utilized for evaluation of new mouse models for CM and UM, as well as for testing new therapies for these diseases.

Clinical and immunohistopathological study of conjunctival melanocytic lesions in pediatric and adolescent patients. A case series.

BACKGROUND: Conjunctival pigmented neoplasia can be benign, premalignant or malignant tumors. Our study aims to establish the epidemiological, gross morphological and immunohistopathological features of the conjunctival pigmented lesions in pediatric and adolescent patients (<18 years), to establish an accurate diagnosis. PATIENTS, MATERIAL AND METHODS: This is a retrospective case series study conducted within two Ophthalmology Clinics from Iasi, Romania, on seven pediatric and adolescent patients. Using the Clinical Observation Chart and the Pathology Registers over a six-years period (January 2015-December 2021), we noted the patients' demographic data, clinical data, and ophthalmological investigations of the lesion, as well as the type of their treatment. All histological sections stained with Hematoxylin-Eosin (HE) and with five antibodies [pan-cytokeratin (pan-CK) AE1∕AE3, S100 protein, Melan A, human melanoma black 45 (HMB45), and Ki67] were re-examined by four pathologists for each case, to identify the type of the conjunctival lesion and its histological and immunohistochemical features. RESULTS: The mean age of all patients was 10.28 years, and the female∕male ratio was 1.3. Right eye was more often affected (71.42%). 71.42% of cases presented an elevated lesion, 57.14% of cases showed a lightly pigmented lesion, but 14.28% of cases exhibited a pink lesion and this feature described the inflamed juvenile conjunctival nevus. In all cases (100%) the conjunctival pigmented tumor was removed with safety margins. The microscopic examination revealed a compound melanocytic nevus in 57.14% cases, a junctional conjunctival nevus in 14.28% cases, an inflamed juvenile nevus in 14.28% cases, and a conjunctival melanoma arising from a pre-existing nevus in 14.28% cases. In all cases of nevi, the nevoid melanocytes showed strong immunopositivity for Melan A and S100 protein, variable and weak immunopositivity for HMB45, and a mean Ki67 labeling index of 1.71%. Conjunctival melanoma revealed strong immunopositivity of tumor cells for HMB45, Melan A and S100 protein, and a Ki67 labeling index of 20%. In all cases, the conjunctival epithelium showed strong immunopositivity for pan-CK AE1∕AE3. All our cases (100%) had a favorable outcome after the surgical removal of the tumor. CONCLUSIONS: Any excision of a conjunctival pigmented lesion must be subject to a systematic immunohistopathological examination, and there is a set of antibodies (anti-HMB45 and anti-Ki67) that are useful for differential diagnosis between a conjunctival nevus and a conjunctival melanoma.

Primary leptomeningeal melanomatosis successfully treated with PD-1 inhibitor pembrolizumab: A case report.

RATIONALE: Primary leptomeningeal melanoma is an extremely rare disease of the central nervous system. There are no standard treatment protocols with a poor prognosis in very few reported cases. Immunotherapy in primary brain melanoma has not been successfully applied so far. PATIENT CONCERNS: We describe a female patient 72-year-old diagnosed in the Neurosurgery Department which presented with generalized seizures. DIAGNOSES: Histological examination confirmed atypical melanocytes immunohistochemically positive for melan A, HMB45 and S-100 protein in the meninges, BRAF V600E negative. Dermatological, ophthalmological examinations, and 18-FDG PET/CT were negative. INTERVENTIONS: The patient was successfully treated with pembrolizumab 2 mg/kg every 3 weeks for 2 years. OUTCOMES: The disease was stable for 2 years and the patient had no significant toxicity. LESSONS: Our report describes durable intracranial tumor response suggesting the efficacy of PD-1 inhibitor pembrolizumab for central nervous system primary leptomeningeal melanoma.

Spindle cell melanoma coexisting with chronic lymphocytic leukemia/small lymphocytic lymphoma: a rare collision tumor in multiple sites.

A strong association has been reported between chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL) and malignant melanoma (MM). In rare cases of MM, lymphoid malignancies may be detected incidentally during sentinel lymph node biopsies. In this case, we found a unique collision of MM and CLL infiltration in the skin. An 88-year-old male patient presented with a mass on the nasal root. Histopathological examination of the skin biopsy specimen revealed a deeply infiltrative, atypical spindle cell proliferation in the background of a collagenous stroma. Accompanying this lesion, there were foci of monotonous lymphoid cell populations involving skin appendages. In the immunohistochemical studies, the spindle cells were diffusely positive for S100, and focally positive for Melan-A and HMB45; the lymphoid cells were positive for CD20, CD5, and Bcl-2 and negative for CD3, Bcl-6, CD10, and Cyclin D1. Histopathological and immunohistochemical findings were consistent with diagnoses of spindle cell melanoma and CLL. Interestingly, these two tumors together in their same morphological appearance were confirmed in a subsequent liver biopsy. Active skin surveillance of patients with CLL may be important to detect MM at an early stage that correlates with a better prognosis.

Four Cases of the Melanotic Variant of Malignant Nerve Sheath Tumour: a Rare, Aggressive Neoplasm in Young Dogs with a Predilection for the Spinal Cord.

Four cases of a rare melanotic variant of malignant nerve sheath tumour (MNST) in dogs are described. All four cases presented with neurological clinical signs due to multicentric, intradural, intra- and extraparenchymal neoplasms that surrounded the spinal and cranial nerves and infiltrated the adjacent spinal cord and brain. The dogs were young (3 months to 3 years of age), all were female and four different breeds were represented. Characteristic histological features were interweaving fascicles of spindle-shaped cells, sometimes with an architecture reminiscent of Antoni A and B patterns. Some spindle cells showed prominent cytoplasmic melanin pigmentation and such cells were positive by Masson-Fontana stain. Immunohistochemistry performed in three cases was positive for S100 and vimentin, strongly positive for melan A in the melanized cells and negative for glial fibrillary acidic protein and periaxin. Non-melanized cells did not express melan A. Transmission electron microscopy findings in one case were consistent with a peripheral nerve sheath tumour and demonstrated cytoplasmic pre-melanosomes and melanosomes. Melanotic variants of MNSTs are rare in animals with only a solitary report of two previous canine cases in the literature.

Lentigo maligna melanoma in situ with neurotropism.

Perineural invasion, or neurotropism, is defined by the presence of cancer cells either within the neuronal sheath or found along the nerves. In melanoma, it is most commonly associated with invasive desmoplastic melanoma, a melanoma that is most commonly associated with malignant melanoma in situ, lentigo maligna type. Initially, perineural invasion was included in the reported Breslow thickness; however, recent data suggest that it should not be included. In this report, we describe a case of malignant melanoma in situ, lentigo maligna type, with associated neurotropism in the absence of invasive component.

In contrast to melanocytes, keratinocytes of normal human adult interfollicular epidermis do not express galectin-1.

INTRODUCTION: Galectins constitute a phylogenetically conserved family of proteins that specifically bind to glycoconjugates bearing ß-galactoside residues. Although galectin-1 (Gal 1), the first identified member of the galectin family, is involved in highly important biological processes at the molecular and cellular level in human skin, its expression in keratinocytes of normal human adult interfollicular epidermis (NHAIE) remains in dispute, whereas that in epidermal melanocytes has drawn very little attention so far. This prompted us to investigate the expression of Gal 1 in the keratinocytes and melanocytes of NHAIE. METHODS: Biopsy specimens obtained from the buttock skin of 23 healthy adult volunteers of both sexes were processed for single and double immunohistochemical staining using antibodies against Gal 1 and Melan-A. RESULTS: In contrast to epidermal melanocytes, which revealed a distinct Gal 1 immunoreactivity, keratinocytes of NHAIE were completely devoid of any expression of this galectin. CONCLUSIONS: This article simultaneously assesses Gal 1 immunoreactivity of keratinocytes and melanocytes in NHAIE for the first time. Our findings may contribute to a better understanding of alterations in Gal 1 expression in various benign and malignant cutaneous disorders and may be of importance for the future design of targeted therapies.

Impact of checkpoint blockade on cancer vaccine-activated CD8+ T cell responses.

Immune and molecular profiling of CD8 T cells of patients receiving DC vaccines expressing three full-length melanoma antigens (MAs) was performed. Antigen expression levels in DCs had no significant impact on T cell or clinical responses. Patients who received checkpoint blockade before DC vaccination had higher baseline MA-specific CD8 T cell responses but no evidence for improved functional responses to the vaccine. Patients who showed the best clinical responses had low PD-1 expression on MA-specific T cells before and after DC vaccination; however, blockade of PD-1 during antigen presentation by DC had minimal functional impact on PD-1high MA-specific T cells. Gene and protein expression analyses in lymphocytes and tumor samples identified critical immunoregulatory pathways, including CTLA-4 and PD-1. High immune checkpoint gene expression networks correlated with inferior clinical outcomes. Soluble serum PD-L2 showed suggestive positive association with improved outcome. These findings show that checkpoint molecular pathways are critical for vaccine outcomes and suggest specific sequencing of vaccine combinations.

Three Types of Nodal Melanocytic Nevi in Sentinel Lymph Nodes of Patients With Melanoma: Pitfalls, Immunohistochemistry, and a Review of the Literature.

The presence or absence of metastasis in sentinel lymph nodes often drives melanoma staging, prognosis, and treatment. However, distinguishing between metastatic melanoma cells and clusters of benign melanocytic nevus cells is not always straightforward. When morphologic hematoxylin and eosin interpretation alone is not sufficient, additional hematoxylin and eosin sections and immunohistochemical (IHC) studies may be beneficial. This review and small cases series of 3 diagnostically challenging melanocytic sentinel lymph node cases highlights the IHC approach to evaluate intraparenchymal nodal melanocytic nevi, coexistent metastatic melanoma with adjacent melanocytic nevi cells, and nodal blue nevi. In challenging cases, cytological morphology of the melanocytes, location within the lymph node, and IHC studies may assist in diagnosis. If these tools yield conflicting results, expert opinion is recommended.