Depth of invasion analysis to predict acral melanoma outcomes.

BACKGROUND: Acral melanoma is a subtype with worse outcomes. The Breslow micrometric measurement is the most critical parameter in planning treatment and predicting outcomes. However, for acral lentiginous melanoma, the value of the Breslow thickness is a matter of debate. Depth of Invasion (DOI) is a well-established measure for staging oral squamous cell carcinoma. OBJECTIVE: This study compared DOI and Breslow thickness for predicting acral melanoma outcomes. METHODS: We performed a retrospective cross-sectional study of 71 acral melanoma lesions subjected to sentinel lymph node biopsy at one Brazilian referral center. RESULTS: Cox model univariate analysis showed that both DOI and Breslow thickness predicted melanoma specific survival (HR 1.12; p = 0.0255 and HR 1.144; p = 0.0006, respectively), although Kaplan Meier curve was only significant for Breslow (χ2 = 5.792; p = 0.0161) and not for DOI (χ2 = 0.2556; p = 0.6132). Sentinel lymph node status and presence or absence of ulceration also predicted specific survival in patients with acral melanoma (χ2 = 6.3514; p = 0.0117 and χ2 = 4.2793; p = 0.0386, respectively). Multivariate analysis, however, demonstrated that Breslow depth was the only independent parameter for predicting acral melanoma specific survival (HR 1.144; p = 0.0006). CONCLUSION: Even though Breslow thickness remains the main predictor for survival in acral melanoma, it is not a perfect parameter. The introduction of DOI in this context opens new perspectives for predicting acral melanoma outcomes.

Vitamin D Receptor and Retinoid X Receptor Alpha in Melanocytic Benign Lesions and Melanoma.

ABSTRACT: Vitamin D receptor (VDR) exerts its biological effects when it heterodimerizes to a nuclear receptor of the retinoid family called retinoid X receptor α (RXRα), stimulating or inhibiting DNA transcription. VDR stimulation by vitamin D analogs led to in vitro antiproliferative effects, and experimental RXRα knockout led to loss of proliferation control in melanoma cells. The aim of this study was to determine VDR and RXRα positivity in melanocytic lesions, compared with normal skin species. By immunohistochemistry assays, nuclear VDR, cytoplasmic VDR, and RXRα and RXRα in keratinocytes surrounding melanocytes were evaluated in 77 controls, 92 intradermal nevi, 54 dysplastic nevi, and 83 melanomas in this retrospective cross-sectional study. Nuclear VDR, cytoplasmic VDR, and RXRα were less expressed in exposed areas ( P < 0.001, P = 0.0006, and P < 0.001, respectively) than covered areas. All melanocytic lesions had loss of VDR and RXRα comparing with the control group. In the melanoma group, nuclear VDR tended to inversely correlate with the Breslow index (r = -0.11, P = 0.29) but directly correlated with histological regression ( P = 0.0293). RXRα inversely correlated with mitosis (r = -0.245; P = 0.0263). We can suggest that sun exposure affected VDR and RXRα immunopositivity. Nuclear VDR tendency of inverse correlation with the Breslow index showed that worse melanomas have a greater loss of VDR. RXRα inversely correlated with mitosis, indicating that RXRα can have a role in proliferation control. VDR and RXRα may participate in the development of melanocytic lesions and be a future target of new studies and directed therapies.

Shall we exclude parapsoriasis from the medical vocabulary?

Since the first description of parapsoriasis more than 100 years ago, parapsoriasis has been a questionable condition and occasionally considered a precursor of cutaneous lymphoma. The name "parapsoriasis" is related to a heterogenous group of diseases that show a distinct clinical presentation; however, the histopathological criteria are not strongly specific. Pathologists do not consider parapsoriasis as a possible histopathological diagnosis, but dermatologists use the term as clinical hypothesis. We aim to provide an historical review of parapsoriasis focusing on histopathological criteria, considering its possible relation with cutaneous skin lymphoma, based on articles from PubMed and standard dermatopathological books. Parapsoriasis does not have well-defined histopathological criteria, so its use should be avoided. Being aware of parapsoriasis complexity, a consensus meeting can help to create a guideline regarding this topic.

Proposal for the applicability of modified Breslow (measured from the basal membrane) as a predictor of survival and sentinel lymph node outcome in patients with cutaneous melanoma.

BACKGROUND: Cutaneous melanoma is a neoplasm with a high mortality rate and risk of metastases to distant organs. The Breslow micrometric measurement is considered the most important factor for evaluating prognosis and management, measured from the granular layer to the deepest portion of the neoplasm. Despite its widespread use, the Breslow thickness measurement has some inaccuracies, such as not considering variations in the thickness of the epidermis in different body locations or when there is ulceration. OBJECTIVE: To evaluate the applicability of a modified Breslow measurement, measured from the basal membrane instead of from the granular layer, in an attempt to predict sentinel lymph node examination outcome and survival of patients with melanoma. METHODS: A retrospective and cross-sectional analysis was carried out based on the evaluation of slides stained with hematoxylin & eosin from 275 cases of melanoma that underwent sentinel lymph node biopsy from 2008 to 2021 at a reference center in Brazil. RESULTS: Analysis of the Cox model to evaluate the impact of the Breslow measurement and the modified Breslow measurement on survival showed that both methods are statistically significant. Logistic regression revealed a significant association between both measurements and the presence of metastasis in sentinel lymph nodes. CONCLUSION: Measuring melanoma depth from the basal membrane (modified Breslow measurement) is capable of predicting survival time and sentinel lymph node outcome, as well as the conventional Breslow measurement.

Evaluation epidermal p53 immunostaining by digital image analysis.

BACKGROUND/PURPOSE: Digital techniques have been developed and validated to assess semiquantitatively immunohistochemical nuclear staining. Currently visual classification is the standard for qualitative nuclear evaluation. Analysis of pixels that represents the immunohistochemical labeling can be more sensitive, reproducible and objective than visual grading. This study compared two semiquantitative techniques of digital image analysis with three techniques of visual analysis imaging to estimate the p53 nuclear immunostaining. METHODS: Sixty-three sun-exposed forearm-skin biopsies were photographed and submitted to three visual analyses of images: the qualitative visual evaluation method (0 to 4 + ), the percentage of labeled nuclei and HSCORE. Digital image analysis was performed using ImageJ 1.45p; the density of nuclei was scored per ephitelial area (DensNU) and the pixel density was established in marked suprabasal epithelium (DensPSB). RESULTS: Statistical significance was found in: the agreement and correlation among the visual estimates of evaluators, correlation among the median visual score of the evaluators, the HSCORE and the percentage of marked nuclei with the DensNU and DensPSB estimates. DensNU was strongly correlated to the percentage of p53-marked nuclei in the epidermis, and DensPSB with the HSCORE. CONCLUSION: The parameters presented herein can be applied in routine analysis of immunohistochemical nuclear staining of epidermis.

Blastoid mantle cell lymphoma: cutaneous infiltration.

Mantle cell lymphoma is an aggressive B-cell, non-Hodgkin's lymphoma, with lymph node or extranodal origin, and a mean survival of three to five years. Skin involvement is rare, secondary and indicates neoplasia dissemination. The authors report a case of a female patient, 69 years old, diagnosed previously, after lymph node and bone marrow biopsy. She was undergoing the second chemotherapy regimen when she showed infiltrated plaque-like lesions, nodules and tumors on the trunk and thigh root. Histopathology and immunohistochemistry demonstrated cutaneous infiltration of the blastoid lymphoma.

Fractal dimension analysis: A new tool for analyzing colony-forming units.

The gold standard for quantifying bacteria both in routine diagnostics and in research is plating followed by count of colony-forming units (CFU). But, manual CFU counting on plates is time-consuming and subjective. We evaluated fractal dimension as a new methodology for evaluating CFU. Twenty fragments of expanded polytetrafluoroethylene (ePTFE) synthetic vascular prosthesis and 20 silicone prostheses were embedded in bacterial suspensions and incubated. The prostheses were then sown in solid culture medium and incubated for 48 h. Petri dishes were photographed and analyzed by fractal dimension. There was correlation between the number of CFU in manual counting and the fractal dimension analysis (p = 0.0001). We demonstrated that fractal dimension is a useful method for microbiological analyses in researches. It makes CFU analysis easier and faster and can be used regardless of the culture medium.•Petri dishes with different bacterial colonies were photographed with a digital camera under natural light.•The images were binarized and analyzed with ImageJⓇ's "fractal dimension" tool.•Fractal dimension analysis showed to be a good tool for evaluating the amount of colony-forming unit.

Does washing medical devices before and after use decrease bacterial contamination?: An in vitro study.

ABSTRACT: Surface treatment of medical devices may be a way of avoiding the need for replacement of these devices and the comorbidities associated with infection. The aim of this study was to evaluate whether pre- and postcontamination washing of 2 prostheses with different textures can decrease bacterial contamination.The following microorganisms were evaluated: Staphylococcus aureus, Staphylococcus epidermidis, Proteus mirabilis and Enterococcus faecalis. Silicone and expanded polytetrafluoroethylene vascular prostheses were used and divided into 3 groups: prostheses contaminated; prostheses contaminated and treated before contamination; and prostheses contaminated and treated after contamination. Treatments were performed with antibiotic solution, chlorhexidine and lidocaine. After one week of incubation, the prostheses were sown in culture medium, which was incubated for 48 hours. The area of colony formation was evaluated by fractal dimension, an image analysis tool.The antibiotic solution inhibited the growth of S epidermidis and chlorhexidine decrease in 53% the colonization density for S aureus in for both prostheses in the pre-washing. In postcontamination washing, the antibiotic solution inhibited the growth of all bacteria evaluated; there was a 60% decrease in the colonization density of S aureus and absence of colonization for E faecalis with chlorhexidine; and lidocaine inhibited the growth of S aureus in both prostheses.Antibiotic solution showed the highest efficiency in inhibiting bacterial growth, especially for S epidermidis, in both washings. Lidocaine was able to reduce colonization by S aureus in post-contamination washing, showing that it can be used as an alternative adjuvant treatment in these cases.

Paracoccidioidomycosis: an uncommon clinical presentation.

Paracoccidoiomycosis is a systemic mycosis with a higher incidence in males with history of exposure to the rural environment; its classic clinical manifestation is an oro-pulmonary lesion. The authors report a case of a female, urban, 76-year-old patient with atypical clinical-dermatological presentation and diagnostic conclusion after histopathological examination. The clinical response was quick and complete after treatment with itraconazole 400mg/day in the first month, decreased to 200mg/day until the sixth month of treatment.

Gnathostomiasis acquired after consumption of raw freshwater fish in the Amazon region: a report of two cases in Brazil.

Gnathostomiasis is a parasitic zoonosis caused by the helminth Gnathostoma spp., acquired through the consumption of raw or undercooked contaminated aquatic animals.The disease is endemic in Southeast Asia and Central America. Two male patients, both middle-aged, presented with single itchy erythemato-edematous plaques on the anterior thorax and left flank. Both had consumed raw fish in the Amazon region. The clinical and epidemiological examinations suggested gnathostomiasis, and treatment with albendazole caused total regression of the lesions. Health teams should be familiar with the disease to provide correct diagnosis. The control strategy should be based on health education for the population.

Case for diagnosis. Noninfectious suppurative panniculitis induced by mesotherapy with deoxycholate.

A 28-year-old white female patient presented with multiple erythematous-to-violaceous, painful, suppurative nodules on the buttocks and thighs that appeared after two weeks of mesotherapy with deoxycholate, caffeine, sunflower liposomes, and sinetrol for localized fat. She was treated for atypical mycobacteriosis, but with no satisfactory response after antibiotic therapy. Bacterial, mycobacterial, and fungal culture were all negative. Histopathologic examination of the biopsy showed noninfectious suppurative panniculitis. It resolved after treatment with methotrexate, prednisone, and hydroxychloroquine. This report highlights the rarity of this complication, the importance of its early recognition, and differentiation with atypical fast growing mycobacterioses.

Lepromatous leprosy, melanoma, and basal cell carcinoma: clinical-histopathologic association.

Cutaneous neoplasms frequently occur in leprosy, but there are few reports of the coexistence of leprosy and basal cell carcinoma in the same lesion. This case reports a 49-year-old male with an ulcerated plaque on the right lateral nasal wall, bright papules on the sternal region, and a blackened plaque on the right temporal region. The nasal and temporal lesions were diagnosed by histopathology as basal cell carcinoma and melanoma, respectively. The sternal lesions were excised with the repair of the "dog ear" which histopathological examination showed macrophages in the dermis parasitized with acid-fast bacilli, confirming the diagnosis of lepromatous leprosy with Fite-Faraco staining. This case report highlights the importance of referring the dog-ear specimen for histopathologic analysis.

American tegumentary leishmaniasis: severe side effects of pentavalent antimonial in a patient with chronic renal failure.

Pentavalent antimonials are the first-line drug treatment for American tegumentary leishmaniasis. We report on a patient with chronic renal failure on hemodialysis who presented with cutaneous lesions of leishmaniasis for four months. The patient was treated with intravenous meglumine under strict nephrological surveillance, but cardiotoxicity, acute pancreatitis, pancytopenia, and cardiogenic shock developed rapidly. Deficient renal clearance of meglumine antimoniate can result in severe toxicity, as observed in this case. These side effects are related to cumulative plasma levels of the drug. Therefore, second-line drugs like amphotericin B are a better choice for patients on dialysis.

Contribution to characterization of skin field cancerization activity: morphometric, chromatin texture, proliferation, and apoptosis aspects.

BACKGROUND: A skin field cancerization is a cutaneous area with subclinical changes resultant from chronic sun exposure, with a higher predisposition to development of pre-neoplastic and neoplastic lesions. So far, there are no well-defined objective parameters that can indicate their degree of activity. OBJECTIVES: To describe and compare morphometric aspects and expression of factors related to apoptosis and cell proliferation in actinic keratosis (AK), in both photoexposed and photoprotected epidermis. METHODS: A cross-sectional study of patients with actinic keratosis in the forearms, biopsied at two points: the actinic keratosis and the axillary region. The biopsies of the actinic keratosis, perilesional area, and axilla were evaluated through keratinocyte intraepithelial neoplasia (KIN), and immunohistochemistry of p53, survivin, and Ki67. Nuclear morphometry of basal layer cells was performed through digital image analysis: entropy, area, perimeter, Ra, fractal dimension, circularity, color intensity, and largest diameter. RESULTS: There were 13 patients included and 38 actinic keratosis biopsied. In morphometry, 1039 nuclei were analyzed, of which 228 represented axillary skin, 396 demonstrated actinic keratosis, and 415 represented the perilesional area to the actinic keratosis. There was a significant difference (p<0.05) in all variables tested for the topographies evaluated. A significant correlation was identified between nucellar morphometric elements, KIN, proliferation markers, and apoptosis. Joint patterns of p53, Ki67, and KIN discriminated the topographies sampled. STUDY LIMITATIONS: This was a cross-sectional study with a small number of patients. CONCLUSIONS: There are patterns of proliferation, resistance to apoptosis, and different cellular morphometrics between photoprotected skin and photoexposed skin. The joint expression of p53, Ki67, and KIN can characterize skin field cancerization activity.

Proposal for the applicability of modified Breslow (measured from the basal membrane) as a predictor of survival and sentinel lymph node outcome in patients with cutaneous melanoma

Abstract Background Cutaneous melanoma is a neoplasm with a high mortality rate and risk of metastases to distant organs. The Breslow micrometric measurement is considered the most important factor for evaluating prognosis and management, measured from the granular layer to the deepest portion of the neoplasm. Despite its widespread use, the Breslow thickness measurement has some inaccuracies, such as not considering variations in the thickness of the epidermis in different body locations or when there is ulceration. Objective To evaluate the applicability of a modified Breslow measurement, measured from the basal membrane instead of from the granular layer, in an attempt to predict sentinel lymph node examination outcome and survival of patients with melanoma. Methods A retrospective and cross-sectional analysis was carried out based on the evaluation of slides stained with hematoxylin & eosin from 275 cases of melanoma that underwent sentinel lymph node biopsy from 2008 to 2021 at a reference center in Brazil. Results Analysis of the Cox model to evaluate the impact of the Breslow measurement and the modified Breslow measurement on survival showed that both methods are statistically significant. Logistic regression revealed a significant association between both measurements and the presence of metastasis in sentinel lymph nodes. Conclusion Measuring melanoma depth from the basal membrane (modified Breslow measurement) is capable of predicting survival time and sentinel lymph node outcome, as well as the conventional Breslow measurement.

Advanced Thyroid Follicular Carcinoma in a Pregnant Woman.

The diagnostic and therapeutic approach for pregnant women with thyroid nodules can present a challenge, especially concerning surgical procedures. In the context of malignant diagnosis, by fine needle aspiration (FNA), during pregnancy, the uncertainty lies in performing surgery. This article reports the case of a 41-year-old pregnant woman in her first gestation, who sought medical care complaining of right shoulder pain. Imaging workup depicted the destruction of the humeral head and involvement of the surrounding soft tissue. She was 20 weeks pregnant. The histological report favored the diagnosis of malignancy and the thyroid as the primary site. At 30 weeks of gestation, the patient underwent a cesarean section, a total thyroidectomy, and total resection of the metastasis. The child was born healthy, but one year after the diagnosis, the patient died. Bone and soft tissue metastasis of thyroid neoplasms are not very common and indicate poor prognosis.

Melanoma: clinical, evolutive and histopathological characteristics of a series of 136 cases.

BACKGROUND: The incidence of melanoma has been increasing in Brazil and all over the world. Despite improvements in diagnosis and treatment, mortality remains unchanged. OBJECTIVE: To associate clinical and histopathological aspects with the evolution of 136 cases of cutaneous melanoma. METHODS: Retrospective cohort study that analyzed all patients diagnosed with melanoma during the period from 2003 to 2011, with at least 4 years follow up. Archived slides were analyzed to study histopathological variables (Breslow, ulceration, mitoses and histological regression). Medical records were used to retrieve clinical variables (age, sex, localization, time of appearance, diameter) and progression (metastases or death). Association measures were assessed by statistical analysis. RESULTS: There was no statistically significant difference between groups according to age. Superficial spreading subtype showed lower Breslow (0.5mm) than acral lentiginous and nodular subtypes (2 and 4.6mm respectively), less ulceration and metastases (9.4% against 50 and 70.6%). Nodular subtype had higher mitoses' median (5.0/mm2) than superficial spreading and lentigo maligna (0.0/mm2, for both). Regression was more frequent in superficial spreading and lentigo maligna subtypes. There were only deaths by melanoma in the acral group, however, there were deaths for other reasons in groups superficial spreading one, acral lentiginous one and lentigo maligna two. STUDY LIMITATIONS: Use of medical records as a source of data to the study. CONCLUSIONS: Superficial spreading subtype presents better prognosis indicators. Histological subtype should be considered in follow-up and treatment protocols of patients with cutaneous melanoma.

Lymphoepithelioma-like carcinoma of the skin.

Primary cutaneous lymphoepithelioma-like carcinoma is a rare disease with low metastatic potential. Its morphologic and pathological features are similar to those of nasopharyngeal lymphoepithelial carcinoma. We report the case of a 60-year-old man with an infrapalpebral pearly papule, measuring 0.6 cm in diameter. The lesion was excised with a clinical hypothesis of basal cell carcinoma or squamous cell carcinoma. Histopathological analysis revealed a malignant neoplasm with syncytial arrangement of cells with vesicular nuclei, associated with dense lymphocytic infiltrate. Immunohistochemistry revealed cytokeratin-positive cells (AE1/AE3) and p63 protein, indicating epithelial histogenesis and squamous differentiation. A negative Epstein-Barr virus test result was achieved by immunohistochemistry. Primary lymphoepithelioma-like carcinoma of the skin is a differential diagnosis of lesions with prominent inflammatory infiltrates.