Thin Amelanotic and Hypomelanotic Melanoma: Clinicopathological and Dermoscopic Features.

Background and Objectives: Amelanotic/hypomelanotic melanomas (AHMs) account for 2-8% of all cutaneous melanomas. Due to their clinical appearance and the lack of specific dermoscopic indicators, AHMs are challenging to diagnose, particularly in thinner cutaneous lesions. The aim of our study was to evaluate the clinicopathological and dermoscopic features of thin AHMs. Identifying the baseline clinical-pathological features and dermoscopic aspects of thin AHMs is crucial to better understand this entity. Materials and Methods: We divided the AHM cohort into two groups based on Breslow thickness: thin (≤1.00 mm) and thick (>1.00 mm). This stratification helped identify any significant clinicopathological differences between the groups. For dermoscopic analysis, we employed the "pattern analysis" approach, which involves a simultaneous and subjective assessment of different criteria. Results: Out of the 2.800 melanomas analyzed for Breslow thickness, 153 were identified as AHMs. Among these, 65 patients presented with thin AHMs and 88 with thick AHMs. Red hair color and phototype II were more prevalent in patients with thin AHMs. The trunk was the most common anatomic site for thin AHMs. Patients with thin AHMs showed a higher number of multiple melanomas. Dermoscopic analysis revealed no significant difference between thin AHMs and thick AHMs, except for a more frequent occurrence of residual reticulum in thin AHMs. Conclusions: Thin AHMs typically affect individuals with lower phototypes and red hair color. These aspects can be related to the higher presence of pheomelanin, which provides limited protection against sun damage. This also correlates with the fact that the trunk, a site commonly exposed to intermittent sun exposure, is the primary anatomical location for thin AHMs. Multiple primary melanomas are more common in patients with thin AHMs, likely due to an intrinsic predisposition as well as greater periodic dermatologic follow-ups in this class of patients. Apart from the presence of residual reticulum, no other significant dermoscopic differences were observed, complicating the differential diagnosis between thin and thick AHMs based on dermoscopy alone.

The combination of dermoscopy and reflectance confocal microscopy increases the diagnostic confidence of amelanotic/hypomelanotic lentigo maligna.

The dermoscopic diagnosis of amelanotic/hypomelanotic lentigo maligna/lentigo maligna melanoma (AHLM/LMM) may be very difficult in its early stages because of lack of pigment. Reflectance confocal microscopy (RCM) is an imaging technique that is especially helpful for the diagnosis of lentigo maligna. To determine the diagnostic performances of dermoscopy and RCM in the diagnosis of AHLM/LMMs we evaluated dermoscopic and RCM images of consecutive cases of histopathologically confirmed AHLM/LMMs, amelanotic/hypomelanotic basal cell carcinoma and squamous cell carcinoma (AHBCCs/AHSCCs), amelanotic/hypomelanotic benign lesions (AHBLs), and actinic keratoses (AKs) from five participating centers. Sensitivity, specificity, accuracy, predictive values, and level of diagnosis confidence were calculated for both diagnostic procedures. Both dermoscopy and RCM showed diagnostic performance >97% in the diagnosis of AHLM/LMMs versus AHBCC/AHSCCs and their combination slightly improved diagnostic performance, with accuracy increasing from 98.0% to 99.1%. Similarly, RCM in combination with dermoscopy showed a tiny increase in the diagnostic performance in the diagnosis of AHLM/LMMs versus AHBLs (accuracy increased from 87.2% to 88.8%) and versus AKs (accuracy increased from 91.4% to 93.4%). Although the increase in diagnostic performance due to RCM was modest, the combination of dermoscopy and RCM greatly increased the level of confidence; high confidence in the diagnosis of AHLM/LMMs versus AHBLs increased from 36.2% with dermoscopy alone to 76.6% with dermoscopy plus RMC. Based on our results, dermoscopy and RCM should be complementary to improve not only diagnostic accuracy but also the level of diagnostic certainty in the diagnosis of AHLM/LMMs.

Variante amelanótica en melanoma cerebral primario: a propósito de un caso / Primary intracranial melanoma, amelanotic variant: Case report

El melanoma cerebral primario es un tumor muy infrecuente (0,07% de las neoplasias primarias del SNC). Generalmente muestra un abundante contenido en melanina, y solo en contadas ocasiones se han descrito variantes hipoamelanóticas. Presentamos el caso de una paciente con clínica de cefalea, paresia braquial izquierda y síndrome lobar frontal. La RM mostró una masa frontal derecha con captación homogénea de contraste. Como tratamiento, se realizó una resección quirúrgica completa. El estudio anatomopatológico fue diagnóstico para melanoma, con muy escaso contenido en melanina y alto índice proliferativo. Se realizó un estudio de extensión exhaustivo para descartar otra localización primaria. Debido a varias complicaciones intercurrentes, la paciente evolucionó desfavorablemente, sin llegar a recibir otros tratamientos. La variante amelanótica de los melanomas cerebrales primarios no ha sido descrita con detalle previamente. Repasamos la literatura al respecto y discutimos los detalles de manejo y diagnóstico de esta entidad clínica (AU)

Primary brain melanoma is a very rare tumour (only 0.07% of primary CNS neoplasms) which usually shows with abundant melanin content; whereas hypo/melanotic variants have been scarcely described. We introduce the case of a female patient with headache, left brachial paresis and frontal lobar syndrome. The MRI image showed a right frontal mass with homogeneous contrast uptake. As treatment, a complete surgical resection was performed. Pathology was diagnostic for melanoma, with very low melanin content and a high proliferative index. A thorough extension study was performed to rule out an extracranial primary origin. Due to several intercurrent complications, the patient evolved unfavorably, not being able to receive further treatment. The amelanotic variant of primary intracranial malignant melanomas has not been described in detail previously. We will review the literature, focusing on the particularities of management and diagnosis of this clinical entity (AU)

Dermoscopy for the Identification of Amelanotic Acral Melanoma.

Acral lentiginous melanoma is commonly misdiagnosed, and when detected late it portends a poor prognosis. Acral lentiginous melanoma can be mistaken for verruca, pyogenic granuloma, poroma, an ulcer, or other benign skin conditions. Patients with acral skin growths often present initially to a podiatric physician or their primary care physician. It is at this point when the growth is triaged as benign or potentially malignant. Dermoscopy aids in this decision making. Historically, dermoscopy training has been geared toward dermatologists, but there is increasing recognition of the need for dermoscopy training in primary care and podiatric medicine. Dermoscopy is particularly helpful in pink (amelanotic) growths, which can lack the traditional clinical findings of melanoma. A literature review of acral melanoma and dermoscopy was performed in PubMed. We also describe a case of amelanotic acral melanoma in a 58-year-old with a rapidly enlarging painful mass on her heel. The lesion was initially thought to be a pyogenic granuloma and was treated with debridement (curettage). She was ultimately seen in the dermatology clinic, and the findings under dermoscopy were worrisome for amelanotic melanoma. Biopsy confirmed the diagnosis. The cancer metastasized, and the patient died less than 2 years later.

Primary intracranial melanoma, amelanotic variant: Case report.

Primary brain melanoma is a very rare tumour (only 0.07% of primary CNS neoplasms) which usually shows with abundant melanin content; whereas hypo/melanotic variants have been scarcely described. We introduce the case of a female patient with headache, left brachial paresis and frontallobar syndrome. The MRI image showed a right frontal mass with homogeneous contrast uptake. As treatment, a complete surgical resection was performed. Pathology was diagnostic for melanoma, with very low melanin content and a high proliferative index. A thorough extension study was performed to rule out an extracranial primary origin. Due to several intercurrent complications, the patient evolved unfavorably, not being able to receive further treatment. The amelanotic variant of primary intracranial malignant melanomas has not been described in detail previously. We will review the literature, focusing on the particularities of management and diagnosis of this clinical entity.

Amelanotic anorectal malignant melanoma in an ulcerative colitis patient: a rare coincidence or a rare association.

Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the gastrointestinal system, known to be associated with increased risk of carcinogenesis. We report the case of a 55-year-old woman, presenting with symptoms of increased bowel frequency, per rectal bleeding and rectal pain with a background of ulcerative colitis (UC). This was presumptively managed as UC flare, with titration of her medications to control the symptoms. However, a flexible sigmoidoscopy revealed an ulceroproliferative lesion in the rectum, which was identified as an amelanotic anorectal malignant melanoma on immunohistochemistry. No local or distant metastases were noted on radiological imaging. The tumour enlarged progressively and was managed with laparotomy and defunctioning stoma followed by palliative chemotherapy and immunotherapy. This is the first such case reported in literature, highlighting the importance of endoscopic assessment and the need to consider other differential diagnosis in patients with symptoms of IBD flare.

Spontaneous subcapsular and perirenal haemorrhage with retroperitoneal haematoma in a patient with ovarian melanoma metastases.

A 47-year-old woman was admitted to our clinic for intensive pain in the left flank region. The transvaginal ultrasound showed a left adnexal solid mass with ascites. She had undergone surgical removal of skin melanoma in 2008, but in September 2019, intracardiac metastasis resulting from it had been discovered. CT performed in March 2020 had been negative for other metastases. A full abdomen ultrasound was not performed. During the night, the patient began to show signs and symptoms of hypovolaemic shock. The patient was urgently transferred to the operating room for a video laparoscopy. A vast left retroperitoneal haematoma was diagnosed along with voluminous enlargement of the left ovary. We proceeded with a left adnexectomy and blood transfusion. Subsequent contrast-enhanced CT revealed a left subcapsular, perirenal haematoma and a voluminous retroperitoneal haematoma. Kidney metastasis was also seen. The final histological diagnosis was metastatic amelanotic malignant melanoma of the ovary.

Clinicopathological and dermoscopic features of amelanotic and hypomelanotic melanoma: a retrospective multicentric study.

BACKGROUND: Amelanotic and hypomelanotic melanoma (AHM) has a higher risk of delayed diagnosis and a significant lower 5-year melanoma-specific survival compared to pigmented melanoma. Our aim was the evaluation of the clinicopathological/dermoscopic features of amelanotic melanoma (AM) and hypomelanotic melanoma (HM). METHODS: All participants had a personal history of AHM. We defined HM as showing clinical/dermoscopic pigmentation in < 25% of the lesion's surface and histopathological focal pigmentation, while AM as melanomas with clinical/dermoscopic and histopathological absence of pigmentation. RESULTS: The most common phenotypic traits among the 145 AHM patients were as follows: phototype II, blue-grey eyes, and dark brown hair. Red hair was present in 23.8% AHM cases (AM = 22.60%; HM = 25.80%). The most affected area was the back (29.5%). A total of 67.1% were classified as AM and 32.9% as HM. The most represented hair colors in AM and HM were, respectively, blonde and dark brown hair. Median Breslow thickness was 1.7 mm, superficial spreading melanoma (SSM) and nodular melanoma (NM) were the most represented histotypes, and mitotic rate > 1 × mm2 was reported in 73.3% cases, and regression was significantly more present in HM. Dermoscopy showed high prevalence of white structureless zones (63.4%), linear looped vessels (58.8%), linear irregular vessels (50.0%), and arborizing vessels (47.2%). Multivariate logistic regression confirmed the association between the presence of pigmentation and the following: histological regression, dermoscopic globules, and arborizing vessels. CONCLUSIONS: Predominance of red hair in AHM patients was not confirmed. AHM affects mostly intermittent sun-exposed body areas. The deeper median Breslow thickness (versus pigmented melanoma), the association of AM with the nodular histotype, and the high mitotic rate highlight the AHM's aggressiveness. HM's higher levels of regression can be explained by the presence of pigmentation, driving the underlying immune response. AHM showed a polymorphous vascular pattern and significant presence of arborizing vessels (especially HM).

The diagnostic accuracy of dermoscopy and reflectance confocal microscopy for amelanotic/hypomelanotic melanoma: a systematic review and meta-analysis.

BACKGROUND: Dermoscopy and reflectance confocal microscopy (RCM) are noninvasive techniques for the diagnosis of skin lesions. Their accuracy for amelanotic/hypomelanotic melanoma (AHM) has not been systematically studied. OBJECTIVES: We aimed to investigate systematically the accuracy of dermoscopy and RCM and to compare the accuracy between them for diagnosing AHM. METHODS: We searched the PubMed, Web of Science, Embase and Cochrane Library databases for eligible studies about dermoscopy, RCM and AHM from inception to 31 June 2019. The quality of the studies was assessed with the Quality Assessment of Diagnostic Accuracy Studies tool. The pooled results were calculated using a random effects model in Stata 14, Meta-DiSc, RevMan 5·3 and SAS 9·4. We also explored the sources of heterogeneity by sensitivity analysis. RESULTS: Seven studies with a total of 1111 lesions were included. The pooled sensitivity and specificity of dermoscopy for the diagnosis of AHM were 61% [95% confidence interval (CI) 0·37-0·81] and 90% (95% CI 0·74-0·97), respectively. The corresponding respective values of RCM for the diagnosis of AHM were 67% (95% CI 0·51-0·81) and 89% (95% CI 0·86-0·92). In three studies including the performance of both RCM and dermoscopy, the relative diagnostic odds ratio of RCM over dermoscopy was 4·69 (95% CI 0·81-27·3) (P = 0·068). CONCLUSIONS: Our study demonstrates that both dermoscopy and RCM offer good diagnostic accuracy with high specificity and moderate sensitivity in the diagnosis of AHM. RCM is more accurate than dermoscopy in diagnosing AHM but the comparison needs to be confirmed. What's already known about this topic? Amelanotic/hypomelanotic melanoma (AHM) is the most lethal skin cancer. The diagnosis of AHM is a great challenge because of its nonspecific clinical manifestation. Early diagnosis can improve the prognosis. Dermoscopy and reflectance confocal microscopy (RCM) have high diagnostic accuracy for pigmented melanoma. What does this study add? Both dermoscopy and RCM offer good diagnostic accuracy with high specificity and moderate sensitivity for AHM. RCM might be more accurate than dermoscopy for diagnosis of AHM. More research on the diagnostic accuracy of dermoscopy and RCM for AHM is required in support of these findings.

Dermoscopy of primary cutaneous B- and T-cell lymphomas and pseudolymphomas presenting as solitary nodules and tumors: a case-control study with histopathologic correlation.

BACKGROUND: Primary cutaneous lymphomas (PCLs) and pseudolymphomas presenting as single pink-red nodules/tumors are highly unspecific and include a wide differential diagnosis. OBJECTIVE: To describe the dermoscopic characteristics of PCL/pseudolymphoma. METHODS: In this retrospective, case-control study, we evaluated the dermoscopic features of patients with solitary PCL/pseudolymphoma tumors and compared them to a control group of non-lymphomatous, nonpigmented, solitary tumors (e.g., basal cell carcinoma, amelanotic melanoma, etc). RESULTS: We included 14 patients with PCL/pseudolymphomas and 35 controls. T-cell and B-cell lymphoma proportions were 28.6% (n = 4) and 71.4% (n = 10), respectively. Compared to controls, most lymphomas presented dermoscopically with orange color (71.4% vs. 14.2%, P < 0.001), follicular plugs (85% vs. 2.8%, P < 0.001), and as  organized lesions (85% vs. 31.4%, P = 0.001). Coexistence of orange color and follicular plugs had an odds ratio (OR) of 2.8 (P < 0.001), highly suggestive of PCL . The kappa index for independent observers was 0.66, 0.49, 0.43 for orange background, follicular plugs, and organized lesion, respectively. Histopathologic correlation was performed in six PCL cases and showed dense diffuse and perifollicular lymphocytic infiltrate in all cases and keratin plugs in five of six cases, possibly correlating with the orange color and the follicular plugs, respectively. CONCLUSION: Primary cutaneous lymphomas/pseudolymphomas present with characteristic dermoscopic findings irrespective of immunohistochemical subtype.

Reflectance confocal microscopy margin mapping and monitoring of an amelanotic melanoma in situ of the ear.

In situ amelanotic melanoma represents a diagnostic and therapeutic challenge for clinicians. Poor demarcation of these lesions often results in repeated therapeutic intervention until appropriate clearance has been achieved. Reflectance confocal microscopy (RCM) is a noninvasive bedside imaging modality which allows real-time visualisation, to a near-histological level, of the epidermis and reticular dermis. We present a case of an amelanotic melanoma in situ in which reflectance confocal microscopy margin mapping allowed for demarcation of the melanocytic proliferation and targeted therapeutic intervention with topical imiquimod. Reflectance confocal microscopy was further utilised for noninvasive assessment of therapeutic response.

Dermoscopy improves diagnostic accuracy for clinically amelanotic nodules.

BACKGROUND/OBJECTIVES: Amelanotic nodular melanomas are notoriously difficult to diagnose and are responsible for a disproportionate burden of melanoma mortality. It is important to distinguish them from other amelanotic nodules. This study aimed to describe the dermoscopic features of a series of nodular melanomas and other amelanotic nodules and to determine whether dermoscopy improves diagnostic accuracy. METHOD: Retrospective analysis of 150 clinically amelanotic nodules with macroscopic and dermoscopic images. RESULTS: In terms of classifying the nodules as malignant, dermoscopy was superior to unaided eye (specificity 89%; 95% CI 71-98% vs 67%; 95% CI 46-83%, P = 0.03). Dermoscopy enhanced sensitivity for the diagnosis of both amelanotic melanoma and SCC. In 19% of cases, using dermoscopy, the most likely diagnosis was changed from incorrect to correct. This included 26% of amelanotic melanomas which had a macroscopic misdiagnosis overturned to the correct diagnosis. Polymorphous vascular structures were more common in malignant nodules. 76% of amelanotic melanomas/Merkel cell carcinomas had polymorphous vessels compared with 38% of SCCs/KAs/BCCs and 22% of benign nodules (P < 0.001). CONCLUSION: Dermoscopy improves diagnostic accuracy for amelanotic melanomas and other amelanotic nodules. Although dermoscopy improves diagnostic accuracy for amelanotic melanomas, these aggressive melanomas remain diagnostically difficult.