Amelanotic Melanoma Research Articles

The role of UVA radiation in ketoprofen-mediated BRAF-mutant amelanotic melanoma cells death – A study at the cellular and molecular level

Malignant melanoma is the cause of 80% of deaths in skin cancer patients. Treatment of melanoma in the 4th stage of clinical advancement, in which inoperable metastasis occur, does not provide sufficient effects. Ketoprofen has phototoxic properties and it can be used as a new treatment option for skin cancers as a part of photochemotherapy.The present study was designed to investigate whether ketoprofen in combination with UVA induces cytotoxic, anti-proliferative and pro-apoptotic effects on melanoma cells.It was stated that co-treatment with 1.0 mM ketoprofen and UVA irradiation disturbed homeostasis of C32 melanoma cells by lowering its vitality (decrease of GSH level). Contrary to C32 cells, melanocytes showed low sensitivity to ketoprofen and UVA radiation, pointing selectivity in the mode of action towards melanoma cells. Co-treatment with ketoprofen and UVA irradiation has cytotoxic and anti-proliferative and pro-apoptotic effect on C32. The co-treatment triggered the DNA fragmentation and changed the cell cycle in C32 cells.In conclusion, it could be stated that local application of ketoprofen in combination with UVA irradiation may be used to support the treatment of melanoma and creates the possibility of reducing the risk of cancer recurrence and metastasis.

Molecular Structure, In Vitro Anticancer Study and Molecular Docking of New Phosphate Derivatives of Betulin.

A series of 30-diethylphosphate derivatives of betulin were synthesized and evaluated for their in vitro cytotoxic activity against human cancer cell lines, such as amelanotic melanoma (C-32), glioblastoma (SNB-19), and two lines of breast cancer (T47D, MDA-MB-231). The molecular structure and activities of the new compounds were also compared with their 29-phosphonate analogs. Compounds 7a and 7b showed the highest activity against C-32 and SNB-19 cell lines. The IC50 values for 7a were 2.15 and 0.91 μM, and, for 7b, they were 0.76 and 0.8 μM for the C-32 and SNB-19 lines, respectively. The most potent compounds, 7a and 7b, were tested for their effects on markers of apoptosis, such as H3, TP53, BAX, and BCL-2. For the whole series of phosphate derivatives, a lipophilicity study was performed, and the ADME parameters were calculated. The most active products were docked to the active site of the EGFR protein. The relative binding affinity of selected phosphate betulin derivatives toward EGFR was compared with standard erlotinib on the basis of ChemScore and KDEEP score. Positively, all derivatives docked inside the cavity and showed significant interactions. Moreover, a molecular dynamics study also reveals that ligands 7a,b form stable complexes and the plateau phase started after 7 ns.

Melanization as unfavorable factor in amelanotic melanoma cell biology

The biology of three amelanotic melanoma cell lines (Ab, B16F10, and A375) of different species origin was analyzed during in vitro induced melanization in these cells. Melanin production was induced by DMEM medium characterized by a high level of L-tyrosine (a basic amino acid for melanogenesis). The biodiversity of amelanotic melanoma cells was confirmed by their different responses to melanogenesis induction; Ab hamster melanomas underwent intensive melanization, mouse B16F10 darkened slightly, while human A375 cells did not show any change in melanin content. Highly melanized Ab cells entered a cell death pathway, while slight melanization did not influence cell biology in a significant way. The rapid and high melanization of Ab cells induced apoptosis documented by phosphatidylserine externalization, caspase activation, and mitochondrial energetic state decrease. Melanoma cell type, culture medium, and time of incubation should be taken into consideration during amelanotic melanoma cell culture in vitro. L-tyrosine, as a concentration-dependent factor presented in the culture media, could stimulate some amelanotic melanoma cell lines (Ab, B16F10) to melanin production. The presence of melanin should be considered in the examination of antimelanoma compounds in vitro, because induction of melanin may interfere or be helpful in the treatment of amelanotic melanoma.

3-O-Methylquercetin from Achyrocline satureioides-cytotoxic activity against A375-derived human melanoma cell lines and its incorporation into cyclodextrins-hydrogels for topical administration.

3-O-Methylquercetin (3OMQ), a natural 3-O-methylflavonoid, was isolated from Achyrocline satureioides and purified using the high-performance counter current chromatography (HPCCC) on a semi-preparative scale. High-purity 3OMQ (98%) was obtained with excellent recovery (81.8% (w/w)) and good yield (190mg/100g of plant). Isolated 3OMQ was evaluated against the A375 human amelanotic melanoma cancer cell line and A375-derived with different degrees of aggressiveness (A375-A7, A375-G10, and A375-PCDNA3). The results showed that 3OMQ reduced the cell viability of all strains, demonstrating time- and dose-dependent responses. 3OMQ was used to obtain hydrogels for the topical treatment of melanoma. Thus, 3OMQ was incorporated into hypromellose hydrogels with/without different cyclodextrins (CDs). The 3OMQ formulations showed permeation/retention in all skin layers, namely stratum corneum, epidermis, and dermis. A significant amount of 3OMQ was found in the replication site of the melanoma cells (epidermis and dermis). Altogether, these results demonstrate that 3OMQ can be isolated from Achyrocline satureioides by HPCCC on a semi-preparative scale and exhibit cytotoxic activity against melanoma cells. Its incorporation into an HPMC hydrogel containing HP-β-CD yielded a formulation with excellent technological and biopharmaceutical characteristics for evaluating the topical management of melanoma.

Globe-salvaging treatment of amelanotic uveal melanoma with posterior extraocular extension

Introduction: Extraocular extension (EOE) of uveal melanoma is rare and generally associated with poor systemic prognosis. Case Report: We report a patient with amelanotic uveal melanoma with an extraocular extension managed with combination of surgical resection of the posterior extraocular extension along with transpupillary thermotherapy (TTT) to the choroidal lesion, thereby salvaging the globe. To the best of our knowledge, we are the first case to report such combination treatment for amelanotic uveal melanoma with posterior extension without evidence of orbital recurrence or systemic metastasis over a follow-up period of thirteen years. Conclusion: Careful resection of the extraocular tumor component along with aggressive treatment of the primary intraocular tumor may achieve globe salvage in carefully selected cases.

Amelanotic melanoma: A challenging cytological diagnosis- A case series

Melanoma is an aggressive malignancy, and early diagnosis and treatment can reduce mortality in patients. A new or changing lesion is the most common warning sign of melanoma. In amelanotic tumors, diagnosis may be delayed. Amelanotic melanoma is a form of melanoma in which malignant cells have little or no pigment. Amelanotic melanoma is classically described as skin coloured but a subset of these tumors are red, pink or erythematous. Typical early lesions present as asymmetrical macular lesions. FNAC may show varied cytomorphology ranging from epithelioid to spindled to plasmacytoid pleomorphic cells with marked anisonucleosis and eosinophilic to basophilic cytoplasm with intranuclear pseudoinclusions and cytoplasmic vacoulations admixed with bi- and multinucleate giant cells. We present a case series of varied presentation of amelanotic melanoma with its cytomorphological features.

13155 Reevaluating the ABCD criteria using a consecutive series of melanomas

The ABCDs of melanoma were previously evaluated in studies that used lesion photographs taken due to a clinician’s suspicion for melanoma, possibly excluding more clinically subtle lesions, including amelanotic melanomas. In addition, these criteria were defined prior to the widespread use of dermoscopy, and thus may reflect a different spectrum of lesions now detected by dermatologists. In our practice, physicians routinely photograph all lesions prior to biopsy, allowing us to evaluate the ABCD criteria using a consecutive series of images of melanoma. We retrospectively reviewed 290 consecutive cases of primary cutaneous melanomas diagnosed within the University of Pittsburgh dermatology department from 01/2014 to 07/2016. In a reader study, three independent dermatologists assessed photographs for ABCD criteria. Among our sample of melanomas, 159 (55%) were in situ and 131 (45%) were invasive, with a median Breslow thickness of 0.55 mm (0.35-0.95). The prevalence of each individual ABCD criterion was 85%, 86%, 71% and 60% respectively. Assigning one point per ABCD criterion, we found that most melanomas had a score of 3 (38%) or 4 (41%). Evaluating dermatologists clinically classified 13 (4.5%) lesions as amelanotic melanomas, 6 of which were invasive, with a median Breslow thickness of 1 (0.3-1.8). Amelanotic melanomas did not differ significantly in ABCD features compared with all other melanomas within our sample. Our study validates, in the post-dermoscopy era, the ABC clinical criteria while suggesting that the D criterion should not be relied upon as heavily as a tool for educating patients and physicians on melanoma detection.

Immunohistochemical study of CD117 in various cutaneous melanocytic lesions.

The aim of the present study was to carried out a comparative immunohistochemical evaluation of CD117 (c-Kit), a biomarker that evaluates both tumor progression and prognosis, in different melanocytic lesions, to emphasize the significance of this biomarker in malignant melanoma (MM). The study was performed on 55 cases, represented by a control group, which included 5 cases of simple nevi and 5 cases of dysplastic nevi, as well as a study group consisting of 35 cases of primary MM and 10 metastases (one intestinal, 3 cutaneous - one satellite and two distant as well as 6 in the lymph nodes). The study group included 15 cases of superficial spreading melanoma (SSM), 10 cases of nodular melanoma (NM), 3 lentigo maligna melanoma (LMM), 3 cases of acral lentiginous melanoma (ALM) and 4 cases of amelanotic MM. CD117 was found to be massively involved in the process of tumorigenesis of cutaneous malignancies, being immunohistochemically undetectable in benign neural lesions, but densely expressed in dysplastic lesions and in situ melanoma areas. In invasive cutaneous MMs, CD117 expression tended to decrease with neoplasia progression proceding into the tumorigenic, vertical growth phase, being lower in the profound dermal component of tumors and in nodular MMs. To eliminate the epidermal barriers and gain a proliferative advantage to allow the transition to the vertical growth phase, it seems that MM should lose expression of c-Kit. Cutaneous metastases were found to express CD117 at a level comparable to their primary tumors, suggesting that other mechanisms interfere directly with the metastatic process and not loss of c-Kit expression by itself. CD117 overexpression in cutaneous melanocytic lesions correlates significantly with increased immunostaining intensity, suggesting that the immunohistochemical evaluation of CD117 may be a good method for screening patients, who could benefit from personalized therapy with tyrosine kinase inhibitors.

UVA Radiation Enhances Lomefloxacin-Mediated Cytotoxic, Growth-Inhibitory and Pro-Apoptotic Effect in Human Melanoma Cells through Excessive Reactive Oxygen Species Generation.

Melanoma, the most dangerous type of cutaneous neoplasia, contributes to about 75% of all skin cancer-related deaths. Thus, searching for new melanoma treatment options is an important field of study. The current study was designed to assess whether the condition of mild and low-dose UVA radiation augments the lomefloxacin-mediated cytotoxic, growth-inhibitory and pro-apoptotic effect of the drug in melanoma cancer cells through excessive oxidative stress generation. C32 amelanotic and COLO829 melanotic (BRAF-mutant) melanoma cell lines were used as an experimental model system. The combined exposure of cells to both lomefloxacin and UVA irradiation caused higher alterations of redox signalling pathways, as shown by intracellular reactive oxygen species overproduction and endogenous glutathione depletion when compared to non-irradiated but lomefloxacin-treated melanoma cells. The obtained results also showed that lomefloxacin decreased both C32 and COLO829 cells’ viability in a concentration-dependent manner. This effect significantly intensified when melanoma cells were exposed to UVA irradiation and the drug. For melanoma cells exposed to lomefloxacin or lomefloxacin co-treatment with UVA irradiation, the concentrations of the drug that decreased the cells’ viability by 50% (EC50) were found to be 0.97, 0.17, 1.01, 0.18 mM, respectively. Moreover, we found that the redox imbalance, mitochondrial membrane potential breakdown, induction of DNA fragmentation, and changes in the melanoma cells’ cell cycle distribution (including G2/M, S as well as Sub-G1-phase blockade) were lomefloxacin in a dose-dependent manner and were significantly augmented by UVA radiation. This is the first experimental work that assesses the impact of excessive reactive oxygen species generation upon UVA radiation exposure on lomefloxacin-mediated cytotoxic, growth-inhibitory and pro-apoptotic effects towards human melanoma cells, indicating the possibility of the usage of this drug in the photochemotherapy of malignant melanoma as an innovative medical treatment option which could improve the effectiveness of therapy. The obtained results also revealed that the redox imbalance intensification mediated by the phototoxic potential of fluoroquinolones may be considered as a more efficient treatment model of malignant melanoma and may constitute the basis for the development of new compounds with a high ability to excessive oxidative stress generation upon UVA radiation in cancer cells.

Effects of curcumin based PDT on the viability and the organization of actin in melanotic (A375) and amelanotic melanoma (C32) – in vitro studies

Curcumin is a turmeric, antioxidative compound, well-known of its anti-cancer properties. Nowadays more and more effort is made in the field of enhancing the efficiency of the anticancer therapies. Combining the photoactive properties of curcumin with the superficial localization of melanoma and photodynamic therapy (PDT) seems to be a promising treatment method.The research focused on the evaluation of the curcumin effectiveness as an anticancer therapeutic agent in the in vitro treatment of melanotic (A375) and amelanotic (C32) melanoma cell lines. Keratinocytes (HaCat) and fibroblasts (HGF) were used to assess the impact of the therapy on the skin tissue. The aim of the study was to investigate the cell death after exposure to light irradiation after preincubation with curcumin. Additionaly the authors analized the interactions between curcumin and the actin cytoskeleton.The cytotoxic effect initiated by curcumin and increased by irradiation confirm the usefulness of the flavonoid in the PDT approach. Depending on curcumin concentration and incubation time, melanoma cells survival rate ranged from: 93.68 % (C32 cell line, 10 μM, 24 h) and 83.47 % (A375 cell line, 10 μM, 24 h) to 8.98 % (C32 cell line, 50 μM, 48 h) and 12.42 % (A375 cell line, 50 μM, 48 h). Moreover, photodynamic therapy with curcumin increased the number of apoptotic and necrotic cells in comparison to incubation with curcumin without irradiation. The study demonstrated that PDT induced caspase-3 overexpression and DNA cleavage in the studied cell lines. The cells revealed decreased proliferation after the therapy due to the actin cytoskeleton rearrangement. Although effective, the therapy remains not selective towards melanoma cells.

Amelanotic Malignant Melanoma in a Himalayan Rex Guinea Pig (Cavia porcellus)

A Himalayan Rex guinea pig was presented with a history of nodular, partially ulcerated masses in the subcutis of the left shoulder. Histological examination revealed a garland-like to nodular, infiltrative neoplastic mass of the epidermis and hair follicle epithelium, which obscured the dermoepidermal junction. Neoplastic cells were immunopositive for S100, PNL-2, vimentin and melan-A antigens. No immunolabelling of CD3, CD79, Iba-1 or pancytokeratin was observed. This is the first detailed description of spontaneous amelanotic malignant melanoma in this species.

Amelanotic melanoma of the head and neck: analysis of tumor characteristics from the National Cancer Database.

Amelanotic melanoma is an extremely rare subtype of cutaneous melanoma. The tumor characteristics are still not well understood, especially for those located in the head and neck. Tumor characteristics of patients diagnosed with amelanotic melanoma of the head and neck (AMHN) from January 1, 2004, to December 31, 2015, were analyzed by querying the National Cancer Database. Characteristics of AMHN were subsequently compared with common malignant melanoma of the head and neck (CMMHN). Three hundred and sixty-eight patients were diagnosed with AMHN, and 69,267 were diagnosed with CMMHN. Of those with AMHN, 128 (34.8%) had melanoma located on the scalp and neck, and 172 (46.7%) were diagnosed with an early disease stage (i.e., 0, I, or II). When compared with CMMHN, patients with AMHN were more likely to be diagnosed after 80years of age (25.3% vs. 18.2%; odds ratio [OR], 3.28; 95% CI, 1.09-9.84; P=0.03), when Breslow depth was between 2.01 and 4.00mm (28.5% vs. 6.5%; OR, 1.92; 95% CI, 1.15-3.19; P=0.01), when ulceration was present (36.7% vs. 9.0%; OR, 1.99; 95% CI, 1.34-2.97; P=0.001), and when mitotic count was 1 or more/mm2 (40.5% vs. 12.8%; OR; 2.53; 95% CI, 1.09-5.89; P=0.03). No statistical difference was found for sex, specific location, stage, or lymph node involvement. Our study determined that AMHN is associated with older age, increased Breslow depth, presence of ulceration, and greater mitotic count when compared with CMMHN.

Abstract A08: The effect of irradiation with curcumin as a possible form of amelanotic melanoma treatment

Abstract Nowadays new medicines are being sought to effectively fight against melanoma. Metabolites of natural compounds have been used for antimelanoma therapy for a long time, but in recent years, new active substances of natural origin have been discovered with proven effects that interfere with the metabolism of tumor cells. The most interesting are compounds exhibiting low toxicity against normal cells, and selective cytotoxicity against cancer cells. One of these compounds is curcumin—a component of turmeric. Curcumin has immunomodulatory, anti-inflammatory, anticancer effects, affects the phase II enzymes and is a potent photosensitizer, thus showing strong potential for use in oncotherapy. Curcumin has been investigated as a potential photosensitizer (PS) in anticancer photodynamic therapy (PDT). The phototoxic effect of curcumin is dependent on proper formulations of the compound because of the lipophilic nature of the molecule and the extremely low water solubility at physiologic conditions. In the present study, the combination of curcumin was investigated in PDT using human melanoma amelanotic cell line (C32) and normal human fibroblasts from primary culture as control cells. The cells were maintained in culture and then treated with curcumin at concentrations of 5-50 μM for 2, 24 and 48. Then cells were irradiated with blue light (20 J/cm2) for 5 minutes and incubated for 24 hours. The efficacy of photodynamic effect was evaluated by viability assay (MTT). Additionally, cell death assay and cellular reactive oxygen species (ROS) assay were assessed. The intracellular distribution of curcumin after different time of incubation was visualized by CLSM method. The results suggest that curcumin may be a potent alternative to commonly used cytostatics. Depending on the curcumin concentration, the cell survival ranged from 18.95% of control cells after incubation with 50 μM curcumin to 0.91% after PDT. It has been shown that PDT with curcumin can increase oxidative stress and number of apoptotic and necrotic cells in comparison to incubation with curcumin without irradiation. The reduced and selective anticancer activity as compared to other drugs can be the basis for the use of curcumin also in complementary treatment of amelanotic melanoma. This study has revealed for the first time that PDT with curcumin appears to represent an efficient alternative for the treatment of amelanotic melanoma through the in situ application of the photosensitizer followed by irradiation of the photosensitizer-loaded area. Thus, the proposed protocol seems to be promising in the amelanotic melanoma, which is extremely resistant to standard chemo- and radiotherapy. Citation Format: Stanislaw Kwiatkowski, Dawid Przystupski, Krzysztof Kotowski, Agata Gorska, Weronika Bartosik, Aleksander Kielbik, Jolanta Saczko, Julita Kulbacka. The effect of irradiation with curcumin as a possible form of amelanotic melanoma treatment [abstract]. In: Proceedings of the AACR Special Conference on Melanoma: From Biology to Target; 2019 Jan 15-18; Houston, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(19 Suppl):Abstract nr A08.

S1742 Not as It Appears: A Case of Amelanotic Anorectal Melanoma

INTRODUCTION: Primary anorectal melanoma (ARM) is a rare entity with anorectal presentation accounting for 0.4- 1.6% of all primary melanomas. ARM has an incidence of 0.5-4% of all anorectal malignancies. It presents after the fifth decade of life with nonspecific complaints. In patients taken for colonoscopy, diagnosis and resection can be difficult as lesions may be amelanotic and spread along submucosal planes. With incidence increasing, it is especially important to recognize ARM as a source of morbidity and mortality. CASE DESCRIPTION/METHODS: Our patient is an 89 yo female with Non-Hodgkin lymphoma presenting with left lower quadrant abdominal pain. Her pain was associated with loose stools and hematochezia attributed to hemorrhoids. The patient endorsed colonoscopy 10 years ago and had no polyps identified on any prior studies. Her labs demonstrated WBC of 71, Hgb of 12 with CT A&P demonstrating thickening and fat stranding at the rectum and splenic flexure. Physical exam was notable for tenderness on palpation of the LLQ, and rectal exam demonstrated a palpable mass proximal to the anal verge. The patient was taken for flexible sigmoidoscopy. Sigmoidoscopy demonstrated a non-bleeding malignant appearing 5 cm mass within the rectum which was non-circumferential, just above the dentate line, with multiple cold forceps biopsies taken. Pathology returned as suspicious for malignant melanoma with sections demonstrating an epithelioid malignancy with scattered pigmented cells. This sample was sent for further evaluation, and demonstrated a subepithelial proliferation of poorly differentiated malignant cells in a sheet like configuration. The nuclei displayed severe pleomorphism and the cytoplasm was granular and eosinophilic with questionable, focal pigmentation. By immunohistochemistry, tumor cells showed Mart-1 and CD31 coexpression with focal S-100 staining. The results were thought to represent a poorly-differentiated malignant melanoma. These findings were discussed with the patient, and it was determined she had a poor prognosis with no option for aggressive treatment. Patient did elect for hospice. DISCUSSION: ARM carries a poor prognosis. This is due to misdiagnosis as hemorrhoids, polyps and other rectal cancer. At the time of diagnosis only 37% of ARM is confined at the anorectal area. Surgical resection is the mainstay of treatment for those with local disease. As ARM spread along submucosal planes and are often beyond complete resection, early recognition of ARM is of the utmost importance.Figure 1.: Rectal mass.Figure 2.: Rectal mass.

Synthesis, Spectroscopic Characterization, Structural Studies, and In Vitro Antitumor Activities of Pyridine-3-carbaldehyde Thiosemicarbazone Derivatives

Eight new thiosemicarbazone derivatives, 6-(1-trifluoroethoxy)pyridine-3-carbaldehyde thiosemicarbazone (1), 6-(4′-fluorophenyl)pyridine-3-carbaldehyde thiosemicarbazone (2), 5-chloro-pyridine-3-carbaldehyde thiosemicarbazone (3), 2-chloro-5-bromo-pyridine-3-carbaldehyde thiosemicarbazone (4), 6-(3′,4′-dimethoxyphenyl)pyridine-3-carbaldehyde thiosemicarbazone (5), 2-chloro-5-fluor-pyridine-3-carbaldehyde thiosemicarbazone, (6), 5-iodo-pyridine-3-carbaldehyde thiosemicarbazone (7), and 6-(3′,5′-dichlorophenyl)pyridine-3-carbaldehyde thiosemicarbazone (8) were synthesized, from the reaction of the corresponding pyridine-3-carbaldehyde with thiosemicarbazide. The synthesized compounds were characterized by ESI-Mass, UV-Vis, IR, and NMR (1H, 13C, 19F) spectroscopic techniques. Molar mass values and spectroscopic data are consistent with the proposed structural formulas. The molecular structure of 7 has been also confirmed by single crystal X-ray diffraction. In the solid state 7 exists in the E conformation about the N2-N3 bond; 7 also presents the E conformation in solution, as evidenced by 1H NMR spectroscopy. The in vitro antitumor activity of the synthesized compounds was studied on six human tumor cell lines: H460 (lung large cell carcinoma), HuTu80 (duodenum adenocarcinoma), DU145 (prostate carcinoma), MCF-7 (breast adenocarcinoma), M-14 (amelanotic melanoma), and HT-29 (colon adenocarcinoma). Furthermore, toxicity studies in 3T3 normal cells were carried out for the prepared compounds. The results were expressed as IC50 and the selectivity index (SI) was calculated. Biological studies revealed that 1 (IC50 = 3.36 to 21.35 μM) displayed the highest antiproliferative activity, as compared to the other tested thiosemicarbazones (IC50 = 40.00 to >582.26 μM) against different types of human tumor cell lines. 1 was found to be about twice as cytotoxic (SI = 1.82) than 5-fluorouracile (5-FU) against the M14 cell line, indicating its efficiency in inhibiting the cell growth even at low concentrations. A slightly less efficient activity was shown by 1 towards the HuTu80 and MCF7 tumor cell lines, as compared to that of 5-FU. Therefore, 1 can be considered as a promising candidate to be used as a pharmacological agent, since it presents significant activity and was found to be more innocuous than the 5-FU anticancer drug against the 3T3 mouse embryo fibroblast cells.

Primary acral amelanotic melanoma: A rare case report.

The aim of the present study was to present a rare case of primary acral amelanotic malignant melanoma (AMM). A 61-year-old man developed an aggressive tumor in the front part of the sole of his left foot, which continued to increase in size for >1 year. The biopsy results revealed epidermis loss, ulcer formation, and the presence of abundant allotropic tumor cells throughout the dermis, with deeply stained nuclei, light reddish cytoplasm and visible multinucleated giant cells with heterogeneous nuclear division. The tumor cells exhibited partial formation of nests and bundled distribution, and there were no observed pigment particles. The diagnosis was confirmed as AMM based on the findings of the histopathological examination and immunohistochemical staining for Ki67 (+++), Melan-A (+++), human melanoma black 45 (+), CD20 (-), cytokeratin (CK)7 (-) and CK5/6 (-).

Risk factors affecting the first metastasis of acral melanoma: Low- pigmentation independently predicts a first lung metastasis

Risk factors affecting the first metastasis of acral melanoma: Low- pigmentation independently predicts a first lung metastasis

A RARE CASE OF AMELANOTIC MELANOMA IN THE ORAL CAVITY

Amelanotic melanoma (AM) is a rare malignant lesion that presents a diagnostic challenge due to its wide clinical presentations, lack of pigmentation, and varied histologic appearances. Immunohistochemistry plays a crucial role in the diagnosis. We report a case of a 45-year-old male patient with a red and bleeding growth on the mandibular gingiva, resembling a pyogenic granuloma. An incisional biopsy was performed, and the histopathologic analysis was characterized by proliferation of nests and sheets of nonpigmented atypical epithelioid and plasmacytoid cells displaying a poorly delimited cytoplasm and hyperchromatic nucleus. Immunohistochemistry showed multifocal staining for melanocytic markers, S100 protein, HMB-45, Melan-A, and Ki-67 (95%). These findings confirmed the diagnosis of AM. The patient was referred to the oncologist who observed disease progression to the lungs, liver, and pancreas. The patient was under palliative care and medical follow-up but died. AM has a poor prognosis, with a high incidence of metastasis, recurrence, and death. Amelanotic melanoma (AM) is a rare malignant lesion that presents a diagnostic challenge due to its wide clinical presentations, lack of pigmentation, and varied histologic appearances. Immunohistochemistry plays a crucial role in the diagnosis. We report a case of a 45-year-old male patient with a red and bleeding growth on the mandibular gingiva, resembling a pyogenic granuloma. An incisional biopsy was performed, and the histopathologic analysis was characterized by proliferation of nests and sheets of nonpigmented atypical epithelioid and plasmacytoid cells displaying a poorly delimited cytoplasm and hyperchromatic nucleus. Immunohistochemistry showed multifocal staining for melanocytic markers, S100 protein, HMB-45, Melan-A, and Ki-67 (95%). These findings confirmed the diagnosis of AM. The patient was referred to the oncologist who observed disease progression to the lungs, liver, and pancreas. The patient was under palliative care and medical follow-up but died. AM has a poor prognosis, with a high incidence of metastasis, recurrence, and death.

AMELANOTIC ORAL MELANOMAS: A SERIES OF 5 CASES

Oral melanoma is a very rare tumor resulting from the malignant transformation of the mucosal melanocytes. We report a series of 5 cases of amelanotic melanomas. The mean age was 57.4 years (ranging from 34 to 77 years). Tumors occurred in the tongue, gingiva, lip, and superior alveolar ridge. Histologically, melanomas showed a proliferation of pleomorphic rhabdoid, fusiform, and epithelioid melanocytes with a variable number of mitosis and absent or very focal melanin deposition. In 2 cases, undifferentiated small, blue, round cells were observed. Lymphoma and sarcoma, not otherwise specified, were considered as differential diagnosis. Immunostainings were performed, and all cases were positive for HMB45 and S-100; 2 cases were negative for Melan A. The patients were treated with surgery and/or chemotherapy (paclitaxel and cisplatin). One of them remains disease-free, 3 died, and 1 was lost in follow-up. In conclusion, amelanotic melanomas are aggressive tumors, and immunohistochemical studies are essential for a proper diagnosis.

PIGMENTED AND AMELANOTIC ORAL MELANOMAS AFFECTING DIFFERENT SITES IN ORAL CAVITY: A RARE CASE REPORT

A 70-year-old male smoker patient presented lesions of different aspects. In palate, a lesion with pigmented macular area and a normochromic nodule was observed. Another erythematous nodule was evident in the anterior region of the mandible, with diagnostical hypothesis of pyogenic granuloma. Incisional biopsy was performed. Histopathological exam of palate lesion showed a melanocytic malignant neoplasm, evidencing anisokaryosis, cellular and nuclear pleomorphism, mitotic figures, supported by scarce fibrous stroma, while mandible lesion evidenced dense proliferation of fusiform and epithelioid cells, with vesicular nuclei and inconspicuous nucleoli, and eosinophilic cytoplasm with imprecise limits. Innumerable typical and atypical mitoses were also visualized. Immunohistochemical analysis of palate lesion showed positivity for S100, Melan A, and HMB-45, while mandible lesion showed positivity for S100, CKpool AE1/AE3, and negativity for Melan A, HMB-45. Microscopic features corroborated with diagnosis of oral melanoma in palate and amelanotic melanoma in mandible. The patient was referred for oncologic treatment.