Is Bartonella sp. infection relevant in hematological malignancies in HIV-negative patients? A literature review.

Bartonelloses are diseases caused by Bartonella sp., transmitted to humans by blood sucking arthropod vectors. Clinical presentations include bacillary angiomatosis, cat scratch disease and atypical forms. We performed a review of cases of bartonelloses and hematological malignancies published in HIV-negative patients. Terms used were Bartonella or Bacillary Angiomatosis and Leukemia, Lymphoma, Multiple Myeloma, or Cancer. Fifteen cases met our criteria. Clinical presentations included bacillary angiomatosis, chronic fever, chronic lymphadenopathy, osteomyelitis, neuroretinitis, chronic anemia and hepatosplenic peliosis. Fourteen patients were asymptomatic after antibiotic therapy, and one died before antibiotic treatment. Clinicians should be suspicious of Bartonella sp. infections in immunocompromised patients.

Mohs micrographic surgery in rare cutaneous tumors: a retrospective study at a Brazilian tertiary university hospital

Abstract Background Mohs micrographic surgery is an established technique in the treatment of cutaneous neoplasms. It offers higher cure rates and the main indications are non-melanoma malignant skin tumors. Few studies have been performed on the treatment of rare tumors through this technique. Objective To study rare skin tumors and rare variants of basal cell carcinoma and squamous cell carcinoma submitted to Mohs micrographic surgery in a tertiary service in relation to frequency, disease-free evolution, and applicability of this surgical procedure for this group of tumors. Methods This was a retrospective observational study including rare skin tumors and less common variants of basal cell carcinoma and squamous cell carcinoma treated using Mohs micrographic surgery, between October 2008 and April 2021. Results During the study period, 437 tumors were treated using Mohs micrographic surgery, and 22 (5%) rare skin tumors were selected. The tumors comprised three dermatofibrosarcomas protuberans, two atypical fibroxanthomas, two spiradenomas, two hypercellular fibrohistiocytomas, one primary cutaneous adenocarcinoma, one trichoblastoma, one porocarcinoma, one chondroid syringoma, one cutaneous angiosarcoma, one Merkel cell carcinoma, and one sebaceous carcinoma. Six other cases of rare basal cell carcinoma variants with trichoepitheliomatous differentiation, metatypical basal cell carcinoma, and clear cell squamous cell carcinoma were included. There were no cases of recurrence after an average of six years of follow-up. Study limitations This is a retrospective study on rare neoplasms carried out in a single referral center, and this surgical technique isn't widely available in the public service. Conclusion This retrospective case series showed that Mohs micrographic surgery is an appropriate treatment for rare skin tumors. They corresponded to 5% of the tumors treated by the technique during a 12-year-period, with no recurrences identified.

Scarring versus Non-Scarring Alopecia: An Interobserver Histopathological Reproducibility Study.

Introduction: Distinguishing scarring (SA) versus non-scarring alopecia (NSA) may not be a simple procedure on either clinical or histopathological views. Aims: We sought to study the interobserver variability in the histopathological assessment of SA versus NSA, including clinical-pathological considerations. Methods: Two dermatopathologists independently interpreted the same set of 100 specimens (89 patients). The samples were serial sectioned and stained by hematoxylin and eosin and Verhöeff methods. The patients' mean age was 46 years, with 13 being males and 76 females. Results: In 16/100 samples, there was no consensus among the two examiners regarding SA versus NSA (weighted kappa = 0.6583; 95% CI); 3/16 patients were re-biopsied, and in the second sample, consensus was reached. In 76/89 patients, the anatomopathological examination was helpful in defining the SA versus NSA subtype. Of the 84 samples in which there was interobserver agreement, 4 which had been considered scarring in the routine pathological report were re-classified as non-scarring, whereas one biopsy, previously diagnosed as non-scarring, was now considered cicatricial due to the newly found areas of lichenoid inflammation in the infundibular epithelium. Discussion: The ideal scalp examination may require deep serial biopsy sectioning, elastic tissue stain, re-biopsy, and strict clinical-evolutive correlation.

Mohs micrographic surgery in rare cutaneous tumors: a retrospective study at a Brazilian tertiary university hospital.

BACKGROUND: Mohs micrographic surgery is an established technique in the treatment of cutaneous neoplasms. It offers higher cure rates and the main indications are non-melanoma malignant skin tumors. Few studies have been performed on the treatment of rare tumors through this technique. OBJECTIVE: To study rare skin tumors and rare variants of basal cell carcinoma and squamous cell carcinoma submitted to Mohs micrographic surgery in a tertiary service in relation to frequency, disease-free evolution, and applicability of this surgical procedure for this group of tumors. METHODS: This was a retrospective observational study including rare skin tumors and less common variants of basal cell carcinoma and squamous cell carcinoma treated using Mohs micrographic surgery, between October 2008 and April 2021. RESULTS: During the study period, 437 tumors were treated using Mohs micrographic surgery, and 22 (5%) rare skin tumors were selected. The tumors comprised three dermatofibrosarcomas protuberans, two atypical fibroxanthomas, two spiradenomas, two hypercellular fibrohistiocytomas, one primary cutaneous adenocarcinoma, one trichoblastoma, one porocarcinoma, one chondroid syringoma, one cutaneous angiosarcoma, one Merkel cell carcinoma, and one sebaceous carcinoma. Six other cases of rare basal cell carcinoma variants with trichoepitheliomatous differentiation, metatypical basal cell carcinoma, and clear cell squamous cell carcinoma were included. There were no cases of recurrence after an average of six years of follow-up. STUDY LIMITATIONS: This is a retrospective study on rare neoplasms carried out in a single referral center, and this surgical technique isn't widely available in the public service. CONCLUSION: This retrospective case series showed that Mohs micrographic surgery is an appropriate treatment for rare skin tumors. They corresponded to 5% of the tumors treated by the technique during a 12-year-period, with no recurrences identified.

Chronic type 2 reaction possibly triggered by an asymptomatic Bartonella henselae infection in a leprosy patient.

As leprosy and leprosy reactions are the most prevalent infectious cause of physical disability, it is important to commit efforts to better understand these chronic reactions. Infections, even when asymptomatic, can trigger leprosy reactions and Bartonella spp. in turn, can cause chronic infections. We presented a case of a 51-year-old man who was admitted presenting with chronic type 2 leprosy reactions. He had a lepromatous form of leprosy that was histologically diagnosed six months after the onset of signs and symptoms compatible with a chronic type 2 reaction. He reported a history of a previous hepatitis B diagnosis. During a 24-month multidrug therapy (MDT), chronic reactions were partially controlled with prednisone and thalidomide. Thirty-three months following the leprosy treatment, he still experienced chronic reactions, and whole bacilli as well as globi were found on a new skin biopsy. Since coinfections can trigger type 2 reactions and the patient had close contact with animals and ticks, we investigated the presence of a Bartonella sp. infection. Bartonella henselae DNA was detected in a skin fragment obtained before the beginning of the leprosy retreatment. However, even after six months of a second leprosy MDT, he continued to experience type 2 chronic reactions. He was admitted to the hospital to undergo an intravenous antibiotic therapy for 14 days and then complete the treatment per os for ten more weeks. Leprosy reactions improved following the treatment for B. henselae. After completing the MDT treatment, he has been accompanied for sixty months with no signs of leprosy or leprosy reactions. The asymptomatic infection by B. henselaein this patient was considered the putative trigger of chronic leprosy reactions and leprosy relapse.

Tratamento cirúrgico exclusivo de linfoma B primário cutâneo da zona marginal: relato de caso / Exclusive surgical treatment of a primary cutaneous marginal zone lymphoma: a case report

Os linfomas B primários cutâneos (LBPCs) são linfomas não Hodgkin, de acometimento exclusivamente cutâneo, e representam 25% dos linfomas primários cutâneos. São divididos, conforme comportamento clínico, em indolentes e intermediários. O tratamento das formas indolentes inclui a cirurgia, a radioterapia e, em casos extensos, o rituximabe. Relata-se o caso de mulher de 57 anos, com placa única no braço esquerdo, com diagnóstico de LBPC da zona marginal, tratado com excisão com margens de segurança de 5mm, sem recidiva após 36 meses de seguimento. A cirurgia é uma alternativa terapêutica com bom resultado clínico, sem impacto na sobrevida livre da doença.

Primary cutaneous B-cell lymphomas are non-Hodgkin lymphomas presenting only in the skin and represent 25% of all primary cutaneous lymphomas. Based on their clinical behavior, they are classified into indolent and intermediate forms. Treatment of indolent forms includes surgery, radiotherapy, and, in extensive disease, rituximab. We report a case of a 57-year-old woman with a single nodule in the left arm treated with surgical excision with 5-mm security margins, without relapse after 36 months. Surgery is a therapeutic option in these lymphomas without compromising disease-free survival.

Chronic type 2 reaction possibly triggered by an asymptomatic Bartonella henselae infection in a leprosy patient

ABSTRACT As leprosy and leprosy reactions are the most prevalent infectious cause of physical disability, it is important to commit efforts to better understand these chronic reactions. Infections, even when asymptomatic, can trigger leprosy reactions and Bartonella spp. in turn, can cause chronic infections. We presented a case of a 51-year-old man who was admitted presenting with chronic type 2 leprosy reactions. He had a lepromatous form of leprosy that was histologically diagnosed six months after the onset of signs and symptoms compatible with a chronic type 2 reaction. He reported a history of a previous hepatitis B diagnosis. During a 24-month multidrug therapy (MDT), chronic reactions were partially controlled with prednisone and thalidomide. Thirty-three months following the leprosy treatment, he still experienced chronic reactions, and whole bacilli as well as globi were found on a new skin biopsy. Since coinfections can trigger type 2 reactions and the patient had close contact with animals and ticks, we investigated the presence of a Bartonella sp. infection. Bartonella henselae DNA was detected in a skin fragment obtained before the beginning of the leprosy retreatment. However, even after six months of a second leprosy MDT, he continued to experience type 2 chronic reactions. He was admitted to the hospital to undergo an intravenous antibiotic therapy for 14 days and then complete the treatment per os for ten more weeks. Leprosy reactions improved following the treatment for B. henselae. After completing the MDT treatment, he has been accompanied for sixty months with no signs of leprosy or leprosy reactions. The asymptomatic infection by B. henselaein this patient was considered the putative trigger of chronic leprosy reactions and leprosy relapse.

Uncommon Pigmented Carcinoma In Situ: Case Report and Brief Review.

Pigmented lesions of the oral mucosa encompass several benign and malignant conditions that may be a matter of concern under both clinical and histopathological views. We reported a case of a 62-year-old woman, presenting with an asymptomatic, deeply pigmented lesion on the soft palate. On examination, it appeared asymmetrical, with irregular borders and an area of ulceration. A biopsy, taken to rule out melanoma, revealed a pigmented carcinoma in situ. Throughout the tumor thickness, numerous interspersed melanocytes were found that did not extend to neighboring epithelium. These were large, richly dendritic, and presented abundance of melanin granules and small nuclei. Mild melanin incontinence was found. Scanty transfer of pigment to dysplastic epithelial cells was found through Fontana Masson staining. On immunohistochemical analyses, there were pancytokeratin-stained tumor epithelial cells; increased cell proliferation throughout the entire thickness of the tumor was emphasized by Ki-67 immunomarking. P16 was negative. The dendritic cells were selectively stained for S-100, HMB45 and Melan A. Wide spectrum in situ hybridization for human papillomavirus (HPV) was negative. Unfortunately, following diagnosis, the patient refused any treatment option. Pigmented squamous cell carcinoma with melanocyte colonization must be taken into account in the differential diagnosis of pigmented lesions of the oral cavity.

Effects of the lower energy and pulse stacking in carbon dioxide laser skin treatment: an objective analysis using second harmonic generation.

PURPOSE: To evaluate the effect of fractional carbon dioxide (CO2) laser treatment using lower power associated with pulse stacking within collagen fibers, using second harmonic generation microscopy and computerized image analysis. METHODS: Twenty male Wistar rats aging eight weeks were used. Each treatment area received a single-pass CO2 fractional laser with different parameters. The 20 animals were divided into two groups and euthanized after 30 and 60 days. Second harmonic generation images were obtained and program ImageJ was utilized to evaluate the collagen organization within all areas. Collagen anisotropy, entropy and optical density were quantified. RESULTS: Increased anisotropy over time was observed in all four areas, but only reached statistical significance (p = 0.0305) when the mildest parameters were used (area four). Entropy decreased over time in all areas, but without significance(p = 0.1779) in area four. Density showed an overtime increase only in area four, but no statistical significance was reached (p = 0.6534). CONCLUSIONS: When combined, the results obtained in this study regarding anisotropy, entropy and density tend to demonstrate that it is possible to achieve collagen remodeling with the use of lower power levels associated with stacked pulses.

Basal cell carcinoma with compromised margins: retrospective study of management, evolution, and prognosis.

BACKGROUND: Non-melanoma skin cancer is the most common type of malignancy in the Western world, and surgical excision is the preferred approach. The approach adopted in the face of incomplete excisions of basal cell carcinoma is still controversial. OBJECTIVES: To compare the number of tumor recurrences after treatment for incompletely excised basal cell carcinoma. METHODS: Selection and statistical analysis of medical records of patients who had compromised margins after excision of basal cell carcinoma in a tertiary hospital from 2008 to 2013. RESULTS: A total of 120 medical records were analyzed; the mean age was 69.6 years, and 50% of the patients were female. The most prevalent histological type was nodular; the mean size was 1.1 cm, and the tumor location with the highest incidence was the nose. The lateral margin was the most frequently positive. Clinical follow-up was more widely adopted; only 40 patients underwent a second surgery. The total number of patients who had tumor recurrence was 34 (28.3%). Only the malar location significantly influenced the incidence of recurrence (p = 0.02). The mean follow-up time was 29.54 months, with no significant difference between the follow-ups, although 32.9% of the patients followed-up clinically showed recurrence, against only 20% of those who underwent a second surgery. STUDY LIMITATIONS: Mean follow-up time of less than five years and sample size. CONCLUSIONS: The presence of compromised margins does not necessarily imply recurrence. Location, tumor size, histological subtype, previous epithelial tumors, and clinical conditions of the patient must be considered when choosing the best treatment option.

Massive iron overload and acute-on-chronic liver failure in a patient with Diamond-Blackfan anaemia: a case report.

BACKGROUND: Genetic anaemias lead us to reflect on the classic 'trolley dilemma', when there are two choices but neither one is satisfactory. Either we do not treat anaemia and the patient suffers from chronic tiredness and fatigue, or we do treat it through blood transfusions, leading to iron overload, which is a quite harmful consequence. CASE PRESENTATION: We present the case of a 34-year-old woman with Diamond-Blackfan anaemia (DBA). Bone marrow stem cell transplantation had not been accessible during her childhood, so she had been submitted to monthly blood transfusions throughout her life, leading to a hepatitis C virus infection (which was treated, achieving a sustained virological response when she was 18 years old), and secondary haemochromatosis. Despite chelation therapy, diffuse iron deposition was occurring in multiple organs, markedly in the heart and liver. Her serum ferritin was higher than 21,000 ng/mL and transferrin saturation reached 102%. When she faced heart decompensation, this congestive condition led to an acute liver injury overlapping pre-existing hepatic fibrosis. She progressed to haemodynamic and hepatic failure, with clinical features of acute-on-chronic liver failure (ACLF). Despite therapeutic optimisation, she died of respiratory insufficiency. An autopsy was performed and revealed the macroscopic and microscopic findings of a massive iron deposition in the liver, heart, lungs, spleen, bone marrow, thyroid and adrenal glands. We found marked advance of liver fibrosis (chronic damage), as well as necrosis of hepatocytes in zone 3 of the Rappaport acinus (acute damage), supporting the hypothesis of ACLF. The main feature responsible for acute liver decompensation seemed to be heart insufficiency. CONCLUSION: This is the first case reporting the sequence: DBA, multiple blood transfusions, secondary haemochromatosis, advanced liver fibrosis, heart failure, ACLF and death. A multidisciplinary team is essential to care for DBA patients, since there is a significant emotional burden related to the disease, which might impair an effective chelation therapy and lead to severe consequences due to iron deposition.

Chronic Venous Insufficiency as a Predisposing Factor for Basal Cell Carcinoma on Legs.

BACKGROUND: The main risk factor associated with basal cell carcinomas (BCCs) is believed to be exposure to ultraviolet radiation (UVR). In the case of lower limb BCC, the frequency is higher in women, possibly because of greater exposure of the leg to UVR. Chronic venous insufficiency (CVI), also more common in women, may have some association with leg BCCs. METHODS: We retrospectively evaluated the histopathological features of leg BCCs removed between 1993 and 2017 in a tertiary referral center. The patients' clinical data were obtained from medical records, considering, in particular, CVI. RESULTS: We selected 149 patients with leg BCCs, predominately occurring in elderly Caucasian women. Of those, 71 had a clinical diagnosis of CVI in whom the clinical tumor size and frequency of recurrences were significantly higher than patients without CVI. There was an association between clinical diagnosis of CVI and histological findings of (1) follicular induction in epidermis and (2) distal sweat duct hyperplasia. CONCLUSIONS: CVI, besides the already known UVR exposure, is probably associated with leg BCCs and may determine a worse BCC course.

Herpes simplex virus mucocutaneous tumoural lesions - Systematic review.

The goal was to characterize the clinical-epidemiological profile of patients with mucocutaneous tumoural herpes simplex virus (MCT HSV) lesions across the world. Two researchers extracted and independently reviewed data from the literature search engine PubMed/MEDLINE through October 2018. From 110 reported patients, the following data were available: the patients' ages ranged from 7 to 76 years; the majority was male (62.73 %-69/110) and immunosuppression was found in 97.25 % (106/109, missing 1) cases, of whom 88 were HIV- related. Lesions size varied from 0.2-13 cm, settling in the anogenital region in 76.36 % (84/110) patients; 84.13 % (53/63, missing 47) complained of pain and multiple recurrences were found in 44.94 % (40/89, missing 21) cases. On clinical basis, the initial hypothesis was neoplasia in 36/53 patients. Histopathological diagnosis was achieved in 90 % (90/100, missing 10) cases and was sample size-dependent. Type 2 HSV was detected in 86.07 % (68/79, missing 31) lesions. MCT HSV lesions recurrence after treatment was reported in 33.96 % (18/53, missing 57) patients. Pathophysiology is poorly understood. Physicians should be aware of MCT HSV lesions in immunosuppressed patients to avoid inappropriate therapeutic strategies.

A Reliable Stem Cell Carrier: An Experimental Study in Wistar Rats.

INTRODUCTION: Treatments based on cell biology need reliable and precise carriers for reaching the desired targets. For that reason, a PDO-based cell carrier was idealized, with the purpose of carrying stem cells to distant sites at room temperature. MATERIALS AND METHODS: Three modalities of the same carrier were evaluated: one containing undifferentiated human dental pulp stem cells (DPSCs); one loaded with stem cells induced to neurogenic differentiation (DPSCNs); and one without cells (Blank). The carriers were implanted in sciatic nerve gaps in 48 Wistar rats that were divided in three groups. Two other rats were included in a SHAM control group. Immunohistochemical, histological and clinical analyses were performed in two, four, six and eight weeks of time. RESULTS: Efficacy of human stem cell transportation at room temperature to rats was attested. Moreover, it was possible to confirm that those cells show tropism for inflamed environments and are also prone to induction of neurogenesis in the first two weeks, vanishing after that period. CONCLUSION: Clinical evaluation of the animals' gait recovery shows a promising perspective of success with the inclusion of stem cell-loaded PDO tubes in nerve gaps, which may be positively compared to previously published studies. NO LEVEL ASSIGNED: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors - www.springer.com/00266.

Second-harmonic generation imaging analysis can help distinguish sarcoidosis from tuberculoid leprosy.

Sarcoidosis and tuberculoid leprosy (TL) are prototypes of granulomatous inflammation in dermatology, which embody one of the histopathology limitations in distinguishing some diseases. Recent advances in the use of nonlinear optical microscopy in skin have enabled techniques, such as second-harmonic generation (SHG), to become powerful tools to study the physical and biochemical properties of skin. We use SHG images to analyze the collagen network, to distinguish differences between sarcoidosis and TL granulomas. SHG images obtained from skin biopsies of 33 patients with TL and 24 with sarcoidosis retrospectively were analyzed using first-order statistics (FOS) and second-order statistics, such as gray-level co-occurrence matrix (GLCM). Among the four parameters evaluated (optical density, entropy, contrast, and second angular moment), only contrast demonstrated statistical significance, being higher in sarcoidosis (p = 0.02; 4908.31 versus 2822.17). The results may indicate insufficient differentiating power for most tested FOS and GLCM parameters in classifying sarcoidosis and TL granulomas, when used individually. But in combination with histopathology (H&E and complementary stains, such as silver and fast acid stains), SHG analysis, like contrast, can contribute to distinguishing between these diseases. This study can provide a way to evaluate collagen distribution in granulomatous diseases.

Dermal vasculature and melanocytic proliferation index in photodamaged skin in the assessment of lateral margins of lentigo maligna and lentigo maligna melanoma.

Lentigo maligna (LM) is the most common subtype of melanoma on the face. When it invades the dermis it is called lentigo maligna melanoma (LMM). Its histological delimitation is controversial due to subjectivity. Analysis of peritumoral vasculature and proliferation index of melanocytes may help to differentiate tumor areas from tumor-free areas, as neoplasia-induced angiogenesis in such scenarios, as well as the higher proliferation index of melanocytes in melanomas, are well established. This work compares the peritumoral vasculature and melanocyte proliferation index of LM and LMM with that of adjacent non-neoplastic skin and sun-damaged skin (control). Forty-three resection cases of LM and LMM were selected retrospectively. Immunohistochemistry was performed for anti-CD31 and anti-CD105 to assess vascularization. Melanocyte proliferation index double labeling was performed using the anti-Melan-A and anti-Ki-67. The Chalkley optical grid was used to quantify blood vessel hotspots. Doubly labeled cells with anti-Melan-A and anti-Ki-67 were counted at tumor, free margin, and control skin. Microvasculature quantification under the melanomas, for both CD31 and CD105, was greater than at the margins of the same specimens (P < 0.0001; P = 0.0001) and greater than control skin (P = 0.0016; P = 0.0027), with higher density for CD31 than CD105. The mean number of double-labeled proliferating melanocytes at the melanoma periphery was greater than at the adjacent free skin and control skin (P = 0.0011). The control skin samples showed the highest CD31-positive vasculature in the head and neck region, with a positive correlation between melanocytic proliferation index and vasculature. The presence of neovascularization (CD105) and proliferating melanocytes (Ki67+/Melan-A+) are suspicious findings for LM/LMM, helping to outline, diagnose, and evaluate tumor margins.