Malignant melanoma is a formidable tumor originating from melanocytes of neural crest origin, found in various anatomical locations, primarily in the skin, followed by the eyes and mucosal membranes. This tumor stands out due to its remarkable phenotypic diversity. Transdifferentiation, the process of differentiation into cell lineages other than the one from which the tumor originated, and phenotypic plasticity, characterized by changes in behavior, morphology, and physiology in response to different environmental conditions, can make melanoma a diagnostic conundrum for unwary pathologists. In this case report, we present a challenging case of melanoma with cartilaginous transdifferentiation to shed light on its clinical, pathological, and molecular aspects.

BACKGROUND: One of the most common malignancies that metastasize to the parotid glands and associated lymph nodes is cutaneous melanoma. Although fine-needle aspiration (FNA) is well established for diagnosing primary salivary gland tumours, there is limited literature on its role in diagnosing metastatic lesions.
OBJECTIVE: This study aims to investigate the cytomorphological features of malignant melanoma diagnosed by FNA in cases presenting with a parotid mass.
METHODS: We present the clinical and cytomorphological findings of four cases. Conventional FNA biopsy smears and cell blocks were performed using standard techniques and for the differential diagnosis, a panel of immunohistochemical markers was used.
RESULTS: The patients included three females and one male, aged 54 to 77. FNA biopsies revealed atypical cells with large, hyperchromatic, pleomorphic nuclei, some of which exhibited prominent nucleoli. Plasmacytoid and oncocytic morphologies were also observed. Numerous mitotic figures were noted. Immunohistochemical staining showed HMB-45, S100 positivity in all cases. SOX10, MART-1 and MITF positivity were also observed. Three of the four patients had no history or suspected lesions of melanoma at the time of FNA diagnosis. The absence of melanin pigment complicated the diagnosis, but immunostains confirmed malignant melanoma.
CONCLUSIONS: Diagnosing malignant melanoma by FNA can be challenging, especially when the melanoma is in an unusual site, cytological findings are ambiguous, and there is no history of cutaneous melanoma. Accurate diagnosis requires a high level of suspicion and the use of appropriate immunohistochemistry.

Adrenal gland metastases from malignant melanoma are a common but poorly characterised condition. Their lack of consistent clinical features and poor response to immune checkpoint inhibitors pose a significant diagnostic and therapeutic challenge to practitioners. This case report describes a 78-year-old male with no prior history of melanoma presenting with nonspecific abdominal symptoms and unintentional weight loss who was found to have undifferentiated bilateral adrenal gland metastases from malignant melanoma. Despite ongoing investigations, the primary site of the adrenal gland metastases remained unknown, prompting the consideration of primary adrenal melanoma as a diagnosis. The patient underwent four cycles of treatment with immune checkpoint inhibitors, nivolumab and ipilimumab, followed by maintenance therapy and subsequent adrenal metastasectomy. Despite therapeutic efforts, the patient\'s tumour was resistant to treatment and became undifferentiated. The patient continued with palliative care until his death, more than three years after the onset of symptoms. The clinical features, pathophysiology, diagnosis, treatment, and prognosis of this patient\'s disease are discussed in detail to help inform the management of similar cases.

An older adult patient was admitted with epigastric pain and vomiting and found to have an abdominal mass, increased cholestatic liver enzymes and markedly elevated serum lactate dehydrogenase (LDH). Imaging revealed extensive liver metastases of unknown primary but also an unusual splenic metastasis diagnosed by liver biopsy as malignant melanoma. The patient became lethargic and developed mental status changes associated with asterixis, abnormal EEG, and increased serum ammonia levels. All reversed with high-dose lactulose and had no alternative explanation other than an unusual hepatic encephalopathy secondary to portosystemic shunts bypassing the extensively metastatic liver.

BACKGROUND: Cutaneous malignant melanomas rarely occur in the eye, usually in the eyelids or the conjunctiva. Conjunctival malignant melanomas are even rarer. Most melanomas are dark in color as they are pigmented. However, amelanotic conjunctival malignant melanomas, a scarce variant of the cancer, can be challenging to diagnose accurately.
METHODS: We present two cases of white Caucasian Swedish-born women who were diagnosed with unilateral amelanotic malignant melanoma in the conjunctiva of the eye. In the first case, the patient was an 81-year-old woman who was suffering from redness and foreign body sensation in the left eye. The initial diagnosis was blepharitis. Three biopsies were taken, which showed malignant melanoma in the eyelid and the conjunctiva. Unfortunately, the eye and the rest of the orbit could not be saved, and the patient had to undergo an orbital exenteration. In the second case, the patient was a 50-year-old woman, and the tumor was localized in the temporal conjunctiva of the left eye. The initial diagnosis was pinguecula, but at the time of surgery, the physician suspected conjunctival intraepithelial neoplasia. The tumor was not completely removed, so adjuvant brachytherapy and local chemotherapy were used. The eye was preserved. No neck and/or lung metastasis was detected in either case at the time of diagnosis.
CONCLUSIONS: Conjunctival amelanotic malignant melanomas should be suspected when tumors are present in the eye and/or the eyelids. By suspecting amelanotic malignant melanoma, the delay in treatment can be shortened. Treating them as soon as possible is essential to minimize the risk of metastasis.

Primary spinal malignant melanoma (PSMM) is a rare cancer of the central nervous system (CNS), and PSMM of the spinal nerve root is even more extraordinary. PSMM of a nerve root can mimic the radiographic appearance of benign nerve sheath tumors, thus resulting in misdiagnosis until tissue diagnosis can be made. A 53-year-old African American woman presented with pain primarily involving the left aspect of her neck and shoulder for 2 years. Magnetic resonance imaging (MRI) of the cervical spine demonstrated a T1-hyperintense, T2-hypointense, homogenously enhancing, dumbbell-shaped, intradural extramedullary mass extending out through the left C2-3 foramen. A midline incision was used to perform a C2 and C3 laminectomy, and the mass was removed from the cavity. The histopathologic profile was consistent with the diagnosis of malignant melanoma. The present case report adds to the 110 cases of PSMM and the 20 cases of PSMM of the spinal nerve root in the existing body of literature. Radiographic and clinical features resemble that of the much more common schwannoma or neurofibroma requiring immunohistochemical analysis for definitive diagnosis. The optimal treatment for PSMM has not yet been defined due to its rarity and it is therefore important to report such cases in order to share our clinical experiences and provide data to other clinicians treating this uncommon disease.

Malignant melanoma is a melanocyte-derived tumor known for its aggressive clinical behavior. Melanocytes originate from the neural crest, which also gives rise to neural tissues. Malignant melanoma can occasionally exhibit neural differentiation. We report a case of a 70-year-old male with malignant melanoma exhibiting neural marker positivity in the absence of typical melanoma markers. The patient initially presented with a dark nodule on his left heel, which was confirmed as malignant melanoma through cytology. Surgical resection and lymph node dissection were performed, revealing atypical melanocytes. Despite postoperative nivolumab treatment, metastases in the brain and lungs were observed. Histological examination of the brain tumor showed neural differentiation markers (thyroid transcription factor 1 (TTF-1), cytokeratin 7 (CK7), AE1/AE3, and epidermal growth factor receptor (EGFR)) with negative melanoma markers. The patient eventually succumbed to the disease despite multiple treatments. An autopsy revealed multiple organ tumors (brain, duodenum, stomach, liver, and bile duct) negative for melanoma markers but positive for neuroendocrine markers (CD56, synaptophysin, and chromogranin A). This case suggests two possibilities: the coexistence of malignant melanoma with neuroendocrine tumors or a transformation of melanoma into a neuroendocrine phenotype. This case highlights the need for clinicians to consider the potential for melanoma to lose typical markers and transform into neuroendocrine cancer.

OBJECTIVE: Malignant melanoma is a tumor with a poor prognosis that can metastasize distally at an early stage. Terrein, a metabolite produced by Aspergillus terreus, suppresses the expression of angiogenin, an angiogenic factor. However, the pharmacological effects of natural terrein have not been elucidated, because only a small amount of terrein can be extracted from large fungal cultures. In this study, we investigated the antineoplastic effects of terrein on human malignant melanoma cells and its underlying mechanisms.
METHODS: Human malignant melanoma cell lines were cultured in the presence of terrein and analyzed. Angiogenin production was evaluated using ELISA. Ribosome biosynthesis was evaluated using silver staining of the nucleolar organizer region. Intracellular signaling pathways were analyzed using western blotting. Malignant melanoma cells were transplanted subcutaneously into the backs of nude mice. The tumors were removed at 5 weeks and analyzed histopathologically.
RESULTS: Terrein inhibited angiogenin expression, proliferation, migration, invasion, and ribosome biosynthesis in malignant melanoma cells. Terrein was shown to inhibit tumor growth and angiogenesis in animal models.
CONCLUSIONS: This study demonstrated that terrein has anti-tumor effects against malignant melanoma. Furthermore, chemically synthesized non-natural terrein can be mass-produced and serve as a novel potential anti-tumor drug candidate.

Despite a great progress in identifying treatment options for patients with malignant melanoma, novel therapies tend to be costly and, in some cases, produce adverse effects forcing the melanoma patients to withdraw drugs. There is a strong need for less expensive drugs with a more favorable spectrum of anticancer actions. This study was designed to assess whether LY-2183240 (a potent inhibitor of both, anandamide cellular reuptake and fatty acid amide hydrolase (FAAH), an enzyme that degrades anandamide) has antiproliferative and cytotoxic effects on various human malignant melanoma cell lines (primary A375 and FM55P, metastatic SK-MEL28 and FM55M2) when administered alone or in combination with docetaxel, paclitaxel, mitoxantrone and cisplatin via the MTT assay. The MTT, LDH and BrdU assays were used to evaluate the potency and safety of LY-2183240, whereas isobolographic analysis of interactions was applied to characterize the interactions of LY-2183240 with the studied chemotherapeutics (docetaxel, paclitaxel, mitoxantrone and cisplatin). The isobolography confirmed that the combinations of LY-2183240 with docetaxel, paclitaxel and mitoxantrone produced additive interactions in all the tested melanoma cell lines. Only two antagonistic interactions for LY-2183240 combined with cisplatin in the A375 and FM55P cell lines were observed by the MTT assay. In conclusion, LY-2183240 can be considered an add-on drug for the treatment of melanoma, when combined with docetaxel, paclitaxel, or mitoxantrone, but not with cisplatin.

Combined tumours are those composed of two benign tumours or a benign and malignant tumour or two malignant tumours occurring within the same tumour population. The incidence of combined tumours is very rare. Due to the rarity of these tumours, their biological behaviour remains unlashed. Incisional biopsy of a 48 years old female patient with single, diffuse tumour mass in the oral cavity showed combined tumour or collision tumour of malignant melanoma and squamous cell carcinoma. This was confirmed with immunohistochemistry study. The incidence of combined tumour of malignant melanoma and squamous cell carcinoma in oral cavity is extremely rare. To the best of our knowledge based on the previous literature records, this is the first case report of its kind where there is incidence in the human oral cavity.