Clinical and Pathological Features of Congenital Hepatic Hemangioma in Children: A Retrospective Analysis.

Objective: We reviewed our experience with congenital hepatic hemangiomas (CHH) to assess the effectiveness of our treatment strategies. Methods: Clinical and pathologic features of children with CHH were reviewed. Results: Twenty-two cases of CHH were collected, 17 were resected and 5 were followed until resolution. In 17 with alpha-feto-protein (AFP) levels, 9 were elevated with 5 decreasing to normal before surgery. In six with tumors under 3 cm, five regressed between 1 and 13 months, one required removal 5 years after initial diagnosis. Postoperative histopathology of 17 cases showed abnormal vascular hyperplasia without lobular architecture. CD34 was expressed in all tumors, glucose transporter 1(Glut1) was negative. Conclusion: If the tumor is less than 3 cm, AFP is normal and there are no obvious complications, the lesion can be followed with regular assessment imaging. Surgical resection is an option in tumors less than 3 cm which have not regressed over time.

Histotyping and grading of endometriosis and its association with clinico-pathological parameters.

Current clinical staging/grading schemes of endometriosis show poor correlation with clinical symptoms and histopathological confirmation is only in half of the clinically suspected endometriosis. In this study, done over an 8-year period, several histological features were analysed including an attempt to grade the severity of endometriosis histologically based on the number of foci per low power field. The components in each focus, the phasing of the glands and stroma, the type of glands (endometrial type or undifferentiated type), and stromal features were all analysed. This study attempts to histologically grade endometriosis while relating it to the clinical manifestations and anatomical location. Eighty cases of endometriosis were included. Most common clinical presentation was cyclical pain (n = 62) and the most common anatomical location was adnexa (n = 50). Histologically, severe endometriosis (>3 foci) was seen in 37 cases. The components were mixed in 68 cases. Well-differentiated glandular pattern was typical (n = 54), while 6 cases had undifferentiated. Proliferative phase was seen in 38 cases. Fibrosis and inflammation were present in 29 and 42 cases, respectively. Significant vascular proliferation and plasma cell infiltrate was noted (n = 35). The severe grade was significantly associated with fibrosis (p = 0.03) and inflammation (p = 0.014). Endometriotic foci, unlike eutopic endometrium, shows significant plasma cell infiltrate and vascular proliferation.IMPACT STATEMENTWhat is already known on this subject? Endometriosis, a chronic inflammatory condition in reproductive age group women. The currently used clinical staging and grading systems show poor correlation with patient symptoms and treatment outcomes. Endometriosis with classical histopathological features pose no diagnostic difficulty, however, there is poor concordance with histopathology. Atypical endometriosis is proposed as potential precursor for endometriosis related neoplasms, however, it remains as a controversial entity.What do the results of this study add? The study identifies the uncommon histological patterns which may be encountered in biopsy samples from clinically identified endometriotic lesions. The recognition of these patterns will reduce clinico-pathological discrepancies. In keeping with the other grading systems, attempts at histological grading did not show any correlation with location or patient symptoms. Atypical features were seen only in two cases and was likely to be reactive in nature.What are the implications of these findings for clinical practice and/or further research? Undifferentiated glandular pattern is often a under-recognized histological pattern. Histological grading of severity was a novel attempt to correlate with clinical parameters. Significant plasma cell infiltrate and vascular proliferation in endometriotic foci, underscores the quest for novel therapeutic targets. This study suggests that the use of non-invasive diagnostic methods like fibroscan/inflammatory markers to clinically identify severe disease should be investigated further.

Glucose-6-phosphate dehydrogenase deficiency contributes to metabolic abnormality and pulmonary hypertension.

We have previously reported that several patients with idiopathic pulmonary hypertension (PH) had different types of G6PD deficiency. However, the role of G6PD in PH is multifactorial because G6PD is involved in controlling oxidative stress, metabolic switch, and red blood cell fragility. To delineate the contribution of G6PD to PH pathogenesis, we utilized a mouse line with decreased expression of G6PD (10% from wild-type level). We confirmed that mice with G6PD deficiency develop spontaneous pulmonary hypertension with pulmonary artery and right heart remodeling. G6PD deficiency resulted in increased free hemoglobin and activation of the p38 pathway, which we recently reported induces the development of PH in the sugen/hypoxia model via endothelial barrier dysfunction. Metabolomics analysis of G6PD deficient mice indicates the switch to alternative metabolic fluxes that feed into the pentose phosphate pathway (PPP), resulting in the upregulation of oxidative stress, fatty acid pathway, and reduction in pyruvate production. Thus, G6PD deficiency did not reduce PPP flux that is important for proliferation but activated collateral pathways at the cost of increased oxidative stress. Indeed, we found the upregulation of myo-inositol oxidase, reduction in GSH/GSSG ratio, and increased nitration in the lungs of G6PD-deficient mice. Increased oxidative stress also results in the activation of PI3K, ERK1/2, and AMPK that contribute to the proliferation of pulmonary vasculature. Therefore, G6PD deficiency has a multimodal effect, including hemolysis, metabolic reprogramming, and oxidative stress leading to the PH phenotype in mice.

Masson's tumor of the breast: Rare differential for new or recurrent breast cancer-Case report, pathology, and review of the literature.

A 66-year-old woman had a new left breast mass with a prior history of a stage IIIC left breast cancer. She had excision of the mass. The pathology noted intravascular papillary endothelial hyperplasia (IPEH) also known as Masson's tumor. Although a benign lesion, this remains in the differential of breast lesions with vascular morphology. IPEH has been described at multiple sites throughout the body. It must be distinguished from angiosarcoma. Although Masson's tumor has been previously documented in the breast, prior treatment for breast cancer presents a diagnostic dilemma. Treatment for the breast cancer may be a contributing event for Masson's tumor.

Papillary endothelial hyperplasia (Masson's tumor) developed in the capsule of the implant in a breast cancer patient treated with mastectomy and radiation therapy.

Papillary endothelial hyperplasia (PEH) is an uncommon benign vascular proliferation appearing in soft tissues in different body areas including the breast, which may be related to radiation therapy. A 48-year-old woman previously treated for breast cancer with mastectomy followed by radiation therapy and reconstruction with an implant presented with a newly developing mass in the implant capsule. Pathological diagnosis was PEH. Imaging features of this rare entity are described, and lesions included in differential diagnosis are discussed.

Impact of topical nifedipine on wound healing in animal model (pig).

BACKGROUND: The human skin is an extremely sophisticated and evolved organ that covers the whole body. External agents or the patient's own diseases can cause skin injuries that can challenge healthcare professionals and impose high social, economic and emotional costs. OBJECTIVES: To evaluate the impact of topical nifedipine on skin wound healing, specifically on polymorphonuclear cells, vascular proliferation, and collagen. METHODS: We used three pigs, and created eight injuries in the dorsal region of each animal. We applied 1%, 10%, and 20% concentration nifedipine creams to four of the wounds in animals 1, 2, and 3 respectively and treated the other twelve wounds with saline solution 0.9% only. We analyzed the presence of polymorphonuclear cells, vascular proliferation, and collagen at six different times (days 1, 3, 7, 14, 21, and 28). RESULTS: The evaluation of polymorphonuclear levels showed mild cell activity at all times in the control group, while in the nifedipine groups, marked levels were more frequent at all times during the experiment. There was a 4.84-fold increase in the chance of marked vascular proliferation (p = 0.019) and, at the same time, a decrease in collagen formation (OR 0.02 / p = 0.005) in animal 3. CONCLUSIONS: Topical NFD may have an impact on skin wound healing mechanisms. Our study showed that polymorphonuclear cells and vascular proliferation increased. We also demonstrated that collagen formation decreased. Therefore, topical NFD may have a positive impact on skin wound healing. Additional studies are needed to confirm our results.

CONTEXTO: A pele humana é um órgão extremamente sofisticado e evoluído que cobre todo o corpo. As lesões cutâneas podem ser causadas por agentes externos ou pelas próprias doenças do paciente, e podem representar um desafio para os profissionais de saúde com altos custos sociais, econômicos e emocionais. OBJETIVOS: Avaliar o impacto da nifedipina tópica na cicatrização de feridas cutâneas, especialmente em relação a polimorfonucleares, proliferação vascular e colágeno. MÉTODOS: Utilizamos três porcos e realizamos oito ferimentos na região dorsal de cada animal. Aplicamos as concentrações de nifedipina creme a 1%, 10% e 20% para os animais 1, 2 e 3, respectivamente, sendo que, em quatro ferimentos, aplicamos o creme e, nos outros quatro ferimentos, apenas soro fisiológico a 0,9%. Analisamos a presença de polimorfonucleares, proliferação vascular e colágeno em seis momentos diferentes (dias 1, 3, 7, 14, 21 e 28). RESULTADOS: A avaliação dos níveis polimorfonucleares mostrou atividade celular discreta em todos os momentos no grupo controle, enquanto nos grupos nifedipina, os níveis marcados foram mais frequentes em todos os momentos do experimento. Houve aumento de 4,84 vezes na chance de uma produção marcada (p = 0,019) da proliferação vascular e, ao mesmo tempo, diminuição da formação do colágeno (odds ratio, OR 0,02; p = 0,005) no animal 3. CONCLUSÕES: A nifedipina tópica pode ter impacto no mecanismo de cicatrização cutânea. Nosso estudo mostrou que há aumento dos polimorfonucleares e da proliferação vascular. Além disso, há diminuição da formação do colágeno. Assim, a nifedipina tópica pode ter impacto positivo na cicatrização das feridas cutâneas. Estudos adicionais são necessários para confirmar nossos resultados.

Poikilodermatous plaque-like hemangioma: Case series of a newly defined entity.

BACKGROUND: We present a distinctive type of acquired vascular proliferation, for which we propose the name of poikilodermatous plaque-like hemangioma. OBJECTIVE: The aim of this study was to summarize the clinical and histopathologic features in a case series of poikilodermatous plaque-like hemangioma. METHODS: Sixteen cases were identified from the routine clinical and referral practices of the authors. Clinical characteristics, including demographic details and clinical morphology, were collated. The salient histopathologic features, including immunohistochemical staining results, were summarized. RESULTS: The lesions were usually solitary erythematous-to-violaceous poikilodermatous plaques on the lower extremities and pelvic girdle, with an indolent clinical course. Mean age of affected patients was 72 (range 58-80) years, and there was a male predominance. Histology comprised a distinctive band-like proliferation of vascular channels suggestive of postcapillary venules within the superficial dermis with a background of fibrosis, edema, and loss of elastic fibers. Despite the clinical atrophic appearance, acanthosis was a frequent finding. LIMITATIONS: Retrospective study. CONCLUSION: Poikilodermatous plaque-like hemangioma is a distinctive and previously undescribed vascular proliferation defined by a constellation of consistent and reproducible clinical and histologic features.

Adenodermatofibroma possessing dilated glandular structures with eccrine features: A case study.

Adenodermatofibroma is a newly recognized variant of dermatofibroma characterized by dense proliferation of fibroblasts and histiocytes admixed with dilated glandular structures showing apocrine secretion. Only five cases of adenodermatofibroma have been reported to date. We report an additional case of adenodermatofibroma on the back of a 67-year-old female. In addition to the dilated glandular structures, nondilated eccrine units were present at the upper periphery of the lesion, above which the normal eccrine glands reside. Although decapitation secretion was observed in the nondilated eccrine units at the upper periphery of the lesion, this was not observed in the dilated glandular structures. The inner cells of the dilated glandular structures were S-100 positive, similar to those of the secretory portion of eccrine glands. We considered the glandular structures in our patient were derived from the entrapped eccrine units. We suggest that the term "apocrine metaplasia" be applied to eccrine units showing decapitation secretion.

Differential impact of diabetes mellitus type II and arterial hypertension on collateral artery growth and concomitant macrophage accumulation.

BACKGROUND: Diabetes mellitus type II and arterial hypertension are major risk factors for peripheral arterial disease and have been considered to reduce collateral growth (arteriogenesis). Collateral growth proceeds through different stages. Vascular proliferation and macrophage accumulation are hallmarks of early collateral growth. MATERIAL AND METHODS: We here compare the impact of arterial hypertension and diabetes mellitus type II on collateral proliferation (Brdu incorporation) and macrophage accumulation (ED 2 staining) as well as collateral vessel function (collateral conductance) in a rat model of peripheral vascular disease (femoral artery occlusion), diabetes mellitus type II (Zucker fatty diabetic rats and Zucker lean rat controls) and arterial hypertension (induced via clip placement around the right renal arteriy). We furthermore tested the impact of monocyte chemoattractant protein-1 (MCP­1) on collateral proliferation and macrophage accumulation in these models RESULTS: Diabetic animals showed reduced vascular proliferation and macrophage accumulation, which however did not translate into a change of collateral conductance. Hypertensive animals on the contrary had reduced collateral conductances without altered macrophage accumulation and only a marginal reduction in collateral proliferation. Infusion of MCP­1 only enhanced vascular proliferation in diabetic animals. CONCLUSIONS: These findings illustrate that impaired monocyte/macrophage recruitment is responsible for reduced collateral growth under diabetic conditions but not in arterial hypertension suggesting that diabetes mellitus in particular affects early stages of collateral growth whereas hypertension has its impact on later remodeling stages. Successful pro-arteriogenic treatment strategies in a patient population that presents with diabetes mellitus and arterial hypertension need to address different stages of collateral growth and thus different molecular and cellular targets simultaneously.

Diffuse dermal angiomatosis of the breast: clinicopathologic study of 5 patients.

BACKGROUND: Diffuse dermal angiomatosis (DDA) is a rare skin condition considered to be a type of reactive angioendotheliomatosis. Histologic features are quite characteristic. It has been reported in association with vaso-occlusive disease, trauma, or underlying hypercoagulability. In the past, it was thought to be most common on the lower extremities. OBJECTIVE: The purpose of this study was to describe the clinical and histologic features of 5 patients with DDA. METHODS: The clinical and histologic features of 5 patients with DDA were evaluated. RESULTS: Five women (47-58 years old) had DDA of the breast. Histologic examination showed a diffuse proliferation of benign endothelial cells between the collagen bundles throughout the dermis. LIMITATIONS: The main limitation of our study is the limited number of patients. CONCLUSION: Involvement of the breast is much more common than previously reported. Smoking seems to be a strong risk factor for the disease. Revascularization, oral corticosteroids, and oral anticoagulation have all been reported to be somewhat successful in the treatment of DDA of the breast.

Poikilodermatous Plaque-like Hemangioma: Case Presentation and Literature Review.

Poikilodermatous plaque-like hemangioma (PPH) is a recently described clinical and pathological entity, with only 18 cases reported in the literature. Although uncommon, this benign condition presents consistent clinical and histological findings. We present a new case of PPH in an 81-year-old male and review the existing literature. The persistence over time and the need to distinguish PPH from more significant lesions underscore the importance of its clinical and pathological recognition.

Breast Hemangiomas: Imaging Features With Histopathology Correlation.

Breast hemangiomas are rare benign vascular lesions. In a previously performed review of approximately 10,000 breast surgical pathology results, roughly 0.15% (15/~10 000) were hemangiomas. Hemangiomas are more frequent in women and have a documented age distribution of 1.5 to 82 years. They are most often subcutaneous or subdermal and anterior to the anterior mammary fascia but may rarely be seen in the pectoralis muscles or chest wall. On imaging, breast hemangiomas typically present as oval or round masses, often measuring less than 2.5 cm, with circumscribed or mostly circumscribed, focally microlobulated margins, equal or high density on mammography, and variable echogenicity on US. Calcifications, including phleboliths, can be seen. Color Doppler US often shows hypovascularity or avascularity. MRI appearance can vary, although hemangiomas are generally T2 hyperintense and T1 hypointense with variable enhancement. Pathologic findings vary by subtype, which include perilobular, capillary, cavernous, and venous hemangiomas. If core biopsy pathology results are benign, without atypia, and concordant with imaging and clinical findings, surgical excision is not routinely indicated. Because of histopathologic overlap with well-differentiated or low-grade angiosarcomas, surgical excision may be necessary for definitive diagnosis. Findings that are more common with angiosarcomas include size greater than 2 cm, hypervascularity on Doppler US, irregular shape, and invasive growth pattern.

Diffuse Dermal Angiomatosis of the Breast.

Diffuse dermal angiomatosis (DDA) is a rare, benign cutaneous disorder that can affect the breasts. Typically, it presents in middle-aged women and is increasingly associated with various risk factors that involve tissue hypoxia. We report this case of classical bilateral DDA of the breasts in a 56-year-old female patient. This case highlights the association of DDA with hypoxia-inducing risk factors, such as smoking. Management of the hypoxic risk factors resulted in the resolution of the bilateral ulceration caused by DDA in this patient. This case report aims to discuss the etiology, risk factors, clinical manifestations, and treatment modalities commonly used to manage this condition.

The molecular mechanism of Gorham syndrome: an update.

Gorham syndrome, also known as "vanishing osteopathy" and "invasive hemangiomatosis," is a rare clinical syndrome whose etiology is unknown and can invade the whole-body skeleton. At present, more than 300 cases have been reported at home and abroad, usually manifesting as spontaneous chronic osteolysis with no periosteal reaction at the lysis site and occult onset, often with fractures, scoliosis, chylothorax, etc. When waiting for medical treatment, the condition is serious, and the prognosis is poor. At present, there is no effective treatment. The main pathological manifestations of Gorham syndrome are the non-neoplastic abnormal proliferation of lymphatic vessels or blood vessels and osteolysis caused by osteoclast proliferation or increased activity. At present, there is no unified conclusion regarding Gorham syndrome's pathogenesis. This paper starts with the two most studied osteolysis methods at present, osteoclast osteolysis and osteolysis caused by vascular and lymphatic proliferation and summarizes the corresponding most possible molecular mechanisms in recent years to provide more ideas for Gorham syndrome treatment.

The Immunohistochemical Assessment of Neoangiogenesis Factors in Squamous Cell Carcinomas and Their Precursors in the Skin.

Cutaneous squamous cell carcinoma (cSCC) is a common skin cancer. Well-limited forms can be easily treated with excision, but locally advanced cancers can, unfortunately, progress to metastasis. However, it is difficult to establish the prognosis for cutaneous squamous cell carcinoma and its potential to metastasize. Therefore, this study aimed to evaluate neoangiogenesis in cSCC, as it plays a major role in the dissemination of neoplasia. A literature review was performed on selected neoangiogenic factors (VEGF, ANG1/2, Notch1, CD31/34/105, EGF, etc.). Most of them, including VEGF, EGFR, and CD105, had more elevated levels in the advanced stages of the lesion. The same is true for Notch1, p53, and TGFß, which are the most frequently mutated tumor suppressors in this type of skin cancer. In addition, the inhibition of some of these markers, using Ang1 analogs, inhibitors of EGFR, TRAF6, or combined inhibitors of EGFR and IGF-IR, may lead to a decrease in tumor size. In conclusion, this literature review identified diagnostic and prognostic markers, as well as possible factors that can be used for the targeted therapy of spinaliomas.

Role of inflammatory cells in pathophysiology and management of diabetic retinopathy.

Diabetic retinopathy (DR) is a sight-threatening complication of diabetes mellitus. Several inflammatory cells and proteins, including macrophages and microglia, cytokines, and vascular endothelial growth factors, are found to play a significant role in the development and progression of DR. Inflammatory cells play a significant role in the earliest changes seen in DR including the breakdown of the blood retinal barrier leading to leakage of blood into the retina. They also have an important role in the pathogenesis of more advanced stage of proliferative diabetic retinopathy, leading to neovascularization, vitreous hemorrhage, and tractional retinal detachment. In this review, we examine the function of numerous inflammatory cells involved in the pathogenesis, progression, and role as a potential therapeutic target in DR. Additionally, we explore the role of inflammation following treatment of DR.

Radiation-induced oral mucositis presenting as atypical vascular proliferation: a case report.

Radiation-induced oral mucositis is an oral mucosal injury caused by radiation ionizing radiation, which often manifests as oral mucosal congestion, erosion, and ulcers. Radiation-induced oral mucositis manifesting as vascular proliferative changes in the oral mucosa has not been reported. We report a case of oral mucosal atypical vascular proliferation after radiotherapy for a malignant maxillofacial tumor. We discussed the mechanism and treatment of aty-pical vascular proliferation in the oral mucosa secondary to radiotherapy, including diagnosis, treatment, and previous literature.

Feasibility of hepatocellular carcinoma treatment based on the tumor microenvironment.

The incidence of liver cancer is extremely high worldwide and poses a serious threat to human life and health. But at present, apart from radiotherapy, chemotherapy, liver transplantation, and early resection, sorafenib was the main systemic therapy proven to have clinical efficacy for unresectable liver cancer (HCC) until 2017. Despite the emerging immunotherapy in the past decade with immune inhibitors such as PD - 1 being approved and applied to clinical treatment, there are still some patients with no response. This review aims to elucidate the mechanisms underlying the tumor microenvironment of hepatocellular carcinoma and thus analyze the effectiveness of targeting the tumor microenvironment to improve the therapeutic efficacy of hepatocellular carcinoma, including the effectiveness and feasibility of immunotherapy, tumor oncolytic viruses and anti-vascular proliferation therapy.