Oculocutaneous albinism (OCA) is a genetic disease caused by disorders in melanin synthesis or distribution. In this descriptive study conducted in a tertiary care pediatric hospital, patients with a clinical diagnosis of OCA and genetic study were retrospectively recruited and underwent dermatological and ophthalmological exam, including optical coherence tomography (OCT) and digital dermoscopy. Our findings revealed milder OCA phenotypic expression in individuals harboring single pathogenic mutations in conjunction with polymorphisms, as well as in those with mutations of uncertain significance. Regardless OCA subgroup, severe phenotypes of OCA were associated with a higher number of mutations/polymorphisms in melanin biosynthesis genes and paler dermoscopic patterns, such as vascular pattern, which was the most common pattern in our series.

BACKGROUND: Perivascular epithelioid cell tumor (PEComa) occurring in the female genital tract are rare, and typically found in the uterine corpus. PEComa occurring in the cervix is extremely rare, and very few cases have been reported till now. Cytological diagnosis of cervical PEComa is even rarer. So far, only two cases of PEComa diagnosed by conventional cervical smears have been reported.
METHODS: A 55-year-old postmenopausal woman presented with abnormal vagina discharge for 3 months. A liquid-based cytology test was performed. Microscopically, some loosely cohesive epithelioid cells were uniform with abundant clear cytoplasm, showing predominantly round or oval nuclei with finely stippled chromatin. Distinct round nucleoli were visible in some cells, notably with numerous melanin pigments in the cytoplasm. The cytopathological features were well correlated with cell block and histopathological findings. Upon immunohistochemistry (IHC), the tumor cells were positive for HMB45 and TFE3, focally positive for MelanA, while negative for muscle marker. Fluorescence in situ hybridization (FISH) confirmed TFE3 gene rearrangement. The final pathological diagnosis was PEComa identified by the liquid-based cytology, cell block, cervical biopsy, IHC and FISH result. The patient underwent a total hysterectomy with bilateral salpingo-oophorectomy and was followed up for 2 years with no evidence of disease.
CONCLUSIONS: The cytologic characteristics of the tumor can provide sufficient clues for PEComa diagnosis, which includes loosely cohesive, epithelioid morphology with abundant clear or eosinophilic cytoplasm, low-grade nuclear atypia, cytoplasmic melanin pigments. This will help cytopathologists to recognize this rare tumor that occurred in the cervix, and the combination of predictive morphology evaluation, immunophenotype, and molecular testing can achieve the definitive diagnosis of PEComa.

OBJECTIVE: Median raphe cyst are uncommon malformations of male genitalia, in which are rarely described melanin pigments or melanocytes; less than ten cases have been reported in literature. The aim of our study is to describe a rare ormations, case of pigmented median raphe cyst of the scrotum, successfully treated in our hospital.
METHODS: A 6-years-old boy underwent surgical removal of a melanocytic lesion of the ventral surface of the scrotum in Day Surgery regimen. He reported no surgical complication or recurrence.
RESULTS: Histology showed multiple cystic nodules, lined by squamous and pluri-stratified columnar epithelium, some of which contained melanic deposits and were anti-MART-positive.
CONCLUSIONS: Even though the first case has been reported in 1985, the etiology of median raphe cysts remains unclear. Infrequently associated with trauma or infections, these lesions seem to origin from an abnormal development of the periurethral glands or atypical closure of the median raphe. Rarely melanin pigments or melanocytes are described in the histological examination, and the cause of the pigmentation is still unknown.
CONCLUSIONS: Median raphe cysts present a non-negligible variety of clinical presentations and histological features. Pigmented ones represent the rarest form: further studies may be necessary to clarify their pathogenesis and describe their clinical evolution.
BACKGROUND: Median raphs, Male genitalia, Malformations.
UNASSIGNED: Le cisti del rafe mediano rappresentano una rara malformazione dei genitali maschili; in pochissimi casi (meno di 10 riportati in letteratura)   presente nella lesione una componente melanocitica o pigmenti di melanina. Lo scopo del nostro studio   quello di descrivere un raro caso di cisti pigmentata del rafe mediano dello scroto, trattata con successo presso il nostro nosocomio.
METHODS: Il paziente, di 6 anni di et , presentava una lesione cistica e melanocitica della superficie ventrale dello scroto;   stato sottoposto ad asportazione della cisti in regime di Day Surgery e non ha mostrato, con un follow-up di 5 anni, alcuna recidiva n  complicanza chirurgica.
UNASSIGNED: L’analisi istologica della lesione ha mostrato multipli noduli cistici, caratterizzati da un epitelio squamoso pluristratificato, che conteneva depositi di melanina ed esprimeva positivit  per anti-MART.
UNASSIGNED: Nonostante il primo caso sia stato descritto nel 1985, l’eziologia delle cisti del rafe mediano risulta ancora ignota. Raramente associati ad infezioni o trauma, tali lesioni sembrerebbero originale da un anomalo sviluppo delle ghiandole periuretrali o da una chiusura patologica del rafe mediano. Solo in pochi casi sono presenti melanociti o pigmenti di melanina all’esame istologico e la causa di tale pigmentazione non   ancora chiara.
CONCLUSIONS: Le cisti del rafe mediano mostrano un’ampia gamma di presentazioni cliniche e di aspetti istologici. Le forme pigmentate rappresentano una minima percentuale: ulteriori studi sono necessari per chiarirne la patogenesi e descriverne la naturale evoluzione clinica.

Object Exclusively dopamine-producing pheochromocytoma/paraganglioma (PPGL) is an extremely rare subtype. In this condition, intratumoral dopamine β-hydroxylase (DBH), which controls the conversion of norepinephrine from dopamine, is impaired, resulting in suppressed norepinephrine and epinephrine production. However, the rarity of this type of PPGL hampers the understanding of its pathophysiology. We therefore conducted genetic and immunohistological analyses of a patient with an exclusively dopamine-producing paraganglioma. Methods Paraganglioma samples from a 52-year-old woman who presented with a 29.6- and 41.5-fold increase in plasma and 24-h urinary dopamine, respectively, but only a minor elevation in the plasma norepinephrine level was subjected to immunohistological and gene expression analyses of catecholamine synthases. Three tumors carrying known somatic PPGL-related gene variants (HRAS, EPAS1) were used as controls. Whole-exome sequencing (WES) was also performed using the patient\'s blood and tumor tissue. Results Surprisingly, the protein expression of DBH was not suppressed, and its mRNA expression was clearly higher in the patient than in the controls. Furthermore, dopa decarboxylase (DDC), which governs the conversion of 3,4-dihydroxyphenyl-L-alanine (L-DOPA) to dopamine, was downregulated at the protein and gene levels. In addition, melanin, which is synthesized by L-DOPA, accumulated in the tumor. WES revealed no PPGL-associated pathogenic germline variants, but a missense somatic variant (c.1798G>T) in CSDE1 was identified. Conclusion Although pre-operative plasma L-DOPA was not measured, our histological and gene expression analyses suggest that L-DOPA, rather than dopamine, might have been overproduced in the tumor. This raises the possibility of pathophysiological heterogeneity in exclusively dopamine-producing PPGL.

UNASSIGNED: Multinucleate cell angiohistiocytoma (MCAH) is a benign vascular and fibrohistiocytic (probably reactive) proliferation with peculiar multinucleate cells which most authors interpret as degenerated macrophages. Several clinical variants of MCAH have been described, some of them with brownish-appearing lesions clinically. However, no histologically identified pigment has been described in the cytoplasm of the multinucleate cells so far. We present a pigmented MCAH with cytoplasmic brownish pigment, which was positive with a Masson-Fontana stain and negative with an iron stain, consistent with melanin, in a 33-year-old woman with multiple papules and plaques on the right elbow, right jawline, and left flank.

UNASSIGNED: Acquired dermal melanocytosis (ADM) is a pigmented lesion caused by melanocytes in the dermis, and it is most often observed on the face of young and middle-aged Asian women. ADM development may be associated with melanin synthesis alterations, but little evidence of its molecular and histological alteration has yet been reported. This study aimed to evaluate ADM in different body locations using different immunohistochemical and chemical staining techniques. This retrospective case series includes consecutive patients confirmed as ADM by biopsy between 2001 and 2018. Patient data and archival images were used to determine the pattern and duration of skin lesions, as confirmed by data analysis of immunohistopathological staining of skin biopsy specimens. A total of 22 ADM patients were included with mean age at diagnosis of 47 years, and 63.6% were female. The most common site was limbs (36.4%), followed by face (27.3%), trunk (22.7%), and scalp (13.6%). Melanin levels were highest in the face and upper extremities and lowest in the trunk. All participants had perivascular distribution of dermal melanocytes, particularly on the face and limbs. The perineural distribution of dermal melanocytes was observed in the lower limbs, with prominent inflammation and fibrosis on the scalp. Dermal melanocytes expressed most markers recognizing melanocytes except for CD117. Analysis of this ADM case series has confirmed that melanin is activated by dermal melanocytes that may aggregate along blood vessels. CD117 may be a useful biomarker by which to identify the migration of epidermal melanocytes.

UNASSIGNED: Cutaneous squamomelanocytic tumor (SMT) is an exceedingly rare cutaneous malignancy characterized by the presence of both squamous cell carcinoma and malignant melanoma within a single tumor. SMT typically presents clinically as keratotic skin papulonodules, most commonly occurring on the face, scalp, or other sun-exposed areas of middle-aged to elderly White male patients. Owing to the rare nature of this tumor, the histogenesis and prognosis remain relatively unclear. Histopathological examination of the tangential biopsy revealed an invasive cutaneous malignancy consisting of 2 distinct yet closely associated atypical cell populations: (1) a population of atypical squamoid epithelial cells arranged in cords and keratin pearls and (2) a population consisting of atypical, spindled cells with fine melanin pigment arranged in confluent sheets. Both populations of atypical cells emanated in an invasive pattern from the underside of the overlying epidermis into the deep dermis. Squamomelanocytic tumors are among the rarer types of collision tumors between 2 malignant lesions as most are basomelanocytic. For most reported SMTs, the melanoma population comprises epithelioid cell morphology, whereas our tumor is composed of spindled cell morphology. In this article, we exemplify a unique case of SMT in an 87-year-old male patient.

BACKGROUND: Gingival pigmentation is a discoloration of the gingiva due to a variety of lesions and conditions associated with several endogenous and exogenous etiologic features.
OBJECTIVE: The purpose of this study is to describe a report of gingival pigmentation in a patient who used doxycycline.
METHODS: A 21-year-old Caucasian female was under dermatological treatment and antibiotic therapy with doxycycline 100 mg (one time a day) for 90 days. She presented brown pigmentation at the gingival margin on the facial surfaces of the upper and lower anterior incisors and premolars. The patient was evaluated by immunohistochemical (S-100, Melan-A, and HMB-45) and histopathologic analyses, and clinical history. Blood levels of malondialdehyde (MDA), glutathione (GSH), and superoxide dismutase (SOD) were analyzed by UV/Vis spectroscopy. The adrenaline, noradrenaline, and dopamine in blood were analyzed by high-performance liquid chromatography (HPLC); dehidroepiandrosterone (DHEA) in serum by radioimmunoassay; and luteinizing hormone (LH) and 25-Hydroxyvitamin D by chemiluminescence. Hematoxylin-eosin stained sections revealed keratinocytes with pigment compatible with melanin. The Fontana-Masson staining was positive in melanophages and in some basal keratinocytes. S-100, Melan A and HMB-45 were confirmed as positive markers of melanocytic differentiation in gingival tissue. We observed a significant increase in malondialdehyde (p˂0.05) and a decrease in superoxide dismutase levels (p˂0.05). The dopamine value was found to be 15 pg/ml (reference value ≤ 10 pg/ml).
CONCLUSIONS: The use of doxycycline is associated with an increase in oxidative stress and of dopamine with melanin pigments in the gingival tissue. This case report showed a cause-effect relationship between exposure to doxycycline and pigmentation of the marginal gingiva.

Malignant melanomas often present with irregular shapes and in multiple shades of brown under white light. Dermoscopy is used to diagnose malignant melanomas; nevertheless, it is often difficult to differentiate malignant melanoma from healthy pigmented skin. The DZ-D100 dermoscope (Casio Computer) is a digital camera equipped with a white light-emitting diode (LED) and a violet LED, which can capture non-polarized/polarized conventional dermoscopy images (CDS) as well as violet-light dermoscopy (VLD) images. Since the absorption wavelength of melanin approaches that of ultraviolet rays, VLD with a wavelength of 405 nm can be used to visualize it. This camera allows three images with the same composition to be captured simultaneously. In this case, we performed dermoscopy with DZ-D100 to determine the surgical resection margins of a melanoma of the heel in a 76-year-old woman. The pale-colored lesions that were difficult to demarcate by CDS were clearly visible by VLD, presenting as dark areas in the grayscale images. Preoperatively determined lesion boundaries with CDS in combination with VLD were histologically more accurate than those with conventional CDS alone. Therefore, the combination of CDS and VLD may reveal the distribution of subtle pigmentation of fine melanin in the skin, making it easier to distinguish between lesions and healthy skin. As one of the limitations, parts of the heel with thick stratum corneum were also observed to be dark gray in the VLD images. Therefore, the evaluation of pigment lesion should be performed by comparing both CDS and VLD.

In the central nervous system, the presence of pigment in astrocytic tumors is rare. Only nine cases were reported in the English literature: one ganglioglioma, one pilocytic astrocytoma, and seven cases of pleomorphic xanthoastrocytoma (PXA). Though squash cytology is a common and useful tool for intraoperative diagnosis during brain tumor surgeries, the cytologic findings of pigmented PXA have not been recorded previously. We present a 32-year-old woman with a mass in her medial right temporal lobe. Intraoperative squash cytology examination demonstrated pleomorphic tumor cells containing cytoplasmic pigment granules. The subsequent tissue section and additional workup revealed a PXA with melanosomal melanin pigment deposits. While conventional PXA has to be differentiated from high-grade tumors such as glioblastoma, in the pigmented variant the presence of pigment can cause further diagnostic confusion with other pigmented tumors, in particular melanoma. It should be added into the differential diagnoses when a brain tumor smear shows nuclear pleomorphism and intracytoplasmic pigment particles.