Vascular Proliferations Research Articles

Castleman’s disease presenting as persistent asymptomatic cervical lymphadenopathy in a child: A very rare disease with atypical presentation

Castlemans disease is a rare atypical lympho-proliferative disorder characterised by enlarged hyperplastic lymphnodes with striking vascular proliferations. A cervical location has very rarely been reported in paediatric literature. It can be unicentric or multicentric. There are mainly four histological variants, hyaline vascular type being the commonest one.Although unicentric Castleman's disease carries a favorable prognosis in children, surgical excision is recommended to confirm the diagnosis and to rule out other causes. We report a case of unicentric cervical Castlemans disease of neck in a 6-years old male child, who came to paediatric ward with history of right sided neck mass since 2yrs. After thorough clinical examination and investigations, complete excision of the mass was done. Histopathological examination confirmed the diagnosis of Castlemans disease-hyaline vascular type. On follow-up for two years no recurrence has been seen.

The Vascular Notch Ligands Delta-Like Ligand 4 (DLL4) and Jagged1 (JAG1) Have Opposing Correlations with Microvascularization but a Uniform Prognostic Effect in Primary Glioblastoma: A Preliminary Study

Delta-like ligand 4 (DLL4) and Jagged1 (JAG1), 2 vascular Notch ligands, are involved in the process of tumor angiogenesis. The present study investigates their relationship with microvascularization and the prognostic effect in primary glioblastoma. Tumor tissues from 61 glioblastomas were analyzed using immunohistochemistry for DLL4/JAG1 expression and microvascular formations. The correlations between DLL4/JAG1 and microvascularization were analyzed. The survival probabilities were computed using the Kaplan-Meier method. The Cox proportional hazards regression model was used for multivariate analysis of time to progression (TTP) and overall survival (OS). The results showed increased DLL4 and JAG1 expression in glioblastoma tissues. Five types of basic microvascular formations, including microvascular sprouting, vascular cluster, vascular garland, glomeruloid vascular proliferation, and vasculogenic mimicry, were detected. Glioblastomas with the type I microvascular pattern (MVP) that displayed prominent microvascular sprouting and vascular clusters tended to have higher DLL4 expression, whereas those with the type II MVP that had numerous vascular garlands, glomeruloid vascular proliferations, and vasculogenic mimicries showed upregulated JAG1 expression. Univariate analysis documented that high DLL4 expression, high JAG1 expression, and type II (MVP) were statistically associated with reduced TTP and OS. Multivariate analysis confirmed high DLL4 expression, high JAG1 expression, and type II MVP as significant prognostic factors for both shorter TTP and OS, independent of age, Karnofsky performance scale, and other molecular markers (vascular endothelial growth factor, Ki67, and P53). DLL4 and JAG1 may have opposing effects on tumor angiogenesis in glioblastoma. The Notch pathway may be a new target for antiangiogenic therapy in glioblastoma.

Hemangioma with dabskoid features: a rare histopathologic variant of acquired hemangioma

Dabska tumor, also known as papillary intralymphatic angioendothelioma (PILA), is a locally aggressive hemangiendothelioma characterized by intravascular papillary proliferations of atypical endothelial cells. Besides PILA, papillary tufts lined by hobnail endothelial cells have been rarely described in vascular proliferations. We report two cases of acquired hemangiomas, which focally showed this finding. We present a 15-year-old male and a 7-year-old girl with erythematous nodules. Both lesions were composed of capillary lobules intermingled with large sinusoidal spaces lined with a single layer of flat endothelial cells, which focally developed intravascular papillary proliferations lined by plump hyperchromatic endothelial cells and a central connective tissue core. Both types of cells were positive with CD31 and ERG and negative for Lyve-1, Prox-1 and podoplanin. Wilm's tumor 1 marker was strongly positive in the capillary hemangioma areas while negative in the intravascular tufts. Both lesions recurred after the first excision but we did not observe further recurrence or evidence of metastasis in the follow-up. In summary, our cases expand the histopathologic findings that may be seen in conventional acquired capillary hemangiomas. The focal presence of dabskoid tufts within an otherwise conventional capillary hemangioma should be not misinterpreted as evidence of malignancy.

Bimodal Treatment of a Huge Hypervascular Neurofibroma on the Groin.

Bimodal Treatment of a Huge Hypervascular Neurofibroma on the Groin.

Effects of pneumoperitoneum preconditioning on endothelial progenitor cells and renal protective mechanism in rats

To explore the pneumoperitoneum-mediated renoprotective effects of preconditioning, mobilizing and homing of endothelial progenitor cells (EPCs) in rats. A total of 40 rats were randomized by a numerical table into 5 groups of gasless (C), pneumoperitoneum injury (Pp), long-term pneumoperitoneum preconditioning (P-L), mid-term pneumoperitoneum preconditioning (P-M) and short-term pneumoperitoneum preconditioning (P-S). C group had a pneumoperitoneum pressure of 0 mmHg; Pp group 15 mmHg, time 60 min; P-L, P-M, P-S groups were deflated and deflated preconditioning before pneumoperitoneum, then the same as Pp group, P-L group: inflation time was 25 min, gas discharge time 10 min; P-M group: 15 min, 10 min; P-S group: 5 min, 10 min. At 24 h post-operation, the animals were sacrificed by destroying cervical spine. And the specimens of venous blood and kidneys were harvested. Also the extent of renal injury, the homing of EPCs, the proliferation and angiogenesis of renal endothelial cell and the expression of angiogenic growth factor were analyzed. Compared with Pp group, P-L, P-M and P-S groups exhibited significant improvements in renal function, morphology and histological score (1.88 ± 0.35, 1.63 ± 0.52, 1.75 ± 0.46 vs 2.38 ± 0.52, all P < 0.05). The histological scores of P-M and P-S groups improved significantly versus P-L group (both P < 0.05). P-M and P-S groups showed no significant difference in histological score (P > 0.05). The number of EPCs in kidneys increased in P-L, P-M and P-S groups versus Pp group (2.18% ± 0.14%, 2.87% ± 0.29%, 2.90% ± 0.24% vs 1.73% ± 0.19%, all P < 0.05). The EPCs numbers of P-M and P-S groups were more than that of P-L group (both P < 0.05). And no significant difference existed between P-M and P-S groups (P > 0.05). Compared with Pp group, EPCs of P-L, P-M and P-S groups markedly increased in kidneys. No significant difference existed between P-M and P-S groups, but P-L group was the lowest. Also there was an up-regulated expression of stromal cell derived factor 1-α in pretreated kidneys versus Pp group (all P < 0.05). And P-M and P-S groups increased markedly. Pneumoperitoneum-mediated preconditioning protects against kidney injury by promoting EPC homing and enhancing endothelial cell and vascular proliferations. And short and medium-term preconditioning protocols are more effective for protecting kidneys.

Diagnostic challenges of oral and cutaneous Kaposi's sarcoma in resource-constrained settings.

Kaposi's sarcoma (KS), caused by HHV-8, is the most frequent HIV-associated malignancy worldwide and remains a major scourge in Sub-Saharan Africa. KS is also endemic in much of Africa. There is a risk of misdiagnosis based solely on clinical appearance and haematoxylin and eosin (H&E) staining, especially with other reactive and neoplastic vascular proliferations which occur in the mouth. This study examined oral and cutaneous biopsies from clinically diagnosed lesions of KS in Kenya, using histopathology supplemented with immunohistochemistry (IHC) and polymerase chain reaction (PCR) for HHV-8 as confirmation of diagnosis. Biopsies of 49 lesions (28 oral, 21 cutaneous) previously diagnosed as 'KS' were re-examined by H&E staining and IHC targeting HHV-8 LANA-1. Positive controls were sections from embedded BCBL-1 cell lines. Negative controls were from three different HHV-8-negative biopsies. Confirmation of HHV-8 immunohistochemistry was sought by PCR and by determining the HHV-8 ORFK1 subtype. Whilst most cases were confirmed, 12 oral and 4 cutaneous lesions displayed clinical and histological features of KS but were negative to HHV-8 IHC. These oral lesions were re-diagnosed as pyogenic granulomata (n = 6), deep mycosis (n = 1), inflamed mucosa (n = 2) or 'uncertain but not KS' (n = 3). Whilst PCR is usually helpful in differentiating HHV-8 disease, all samples were HHV-8 PCR positive, with identical sequences, suggesting cross-contamination of samples in the original pathology laboratories. HHV-8 IHC is essential for the correct diagnosis of KS, but due to the high level of contamination in resource-poor settings, PCR is inadvisable.

Distinctive immunohistochemical staining in littoral cell angioma using ERG and WT-1.

Littoral cell angioma (LCA) is a rare vascular tumor of the spleen. It has an immunohistochemical staining pattern that is somewhat distinctive but can still be occasionally confused with other vascular and stromal proliferations in the spleen. In this study, LCA was evaluated using Ets-related gene (ERG) and Wilms tumor-1 (WT-1), relatively recently described vascular markers. In addition, other vascular lesions including normal spleen, hemangiomas, hamartoma, peliosis, and sclerosing angiomatoid nodular transformation were evaluated using these stains. In LCA, ERG stains the endothelial cells of the tumor as expected. ERG also was uniformly positive in vascular elements of other lesions except peliosis. However, in contrast to most other vascular elements, LCA was negative for WT-1 staining. This staining pattern may prove useful in diagnosing LCA and may provide insight into the derivation of the distinctive tumor.

Early Onset Post-Radiation Cutaneous Angiosarcoma of the Breast with Features of Atypical-Vascular Lesion: A Diagnostic Pitfall and Its Biologic Significance

Vascular proliferations may arise in the breast following radiation treatment for a primary breast adenocarcinoma. A post-radiation vascular proliferation can usually be classified as angiosarcoma or as an atypical vascular lesion (AVL). Angiosarcomas with a “low-grade” morphology, behave aggressively but exhibit substantial histomorphologic overlap with AVLs, which have a generally benign clinical course. We present a case of a post-radiation angiosarcoma of the breast with histologic features that mimic an atypical vascular lesion and discuss this challenging differential diagnosis. In addition to histologic mimicry, the lesion exhibited only patchy amplification of the avian myelocytomatosis viral oncogene homolog (MYC) gene by present fluorescence in-situ hybridization (FISH), and patchy MYC overexpression by immunohistochemistry. These features further complicate the distinction between AVL and angiosarcoma, and would be particularly problematic on a small biopsy. We believe that the morphologic and immunohistochemical overlap between these entities is suggestive of a biologic spectrum, and thus that, at least in some instances, angiosarcoma may arise from a pre-existing AVL or AVL-like lesion.

Spindle cell hemangioma of femur

Spindle cell hemangioma (SCH) an uncommon vascular tumor typically appears as solitary or multiple cutaneous and subcutaneous nodules in middle-aged adults. Its occurrence in bone is extremely rare. We report a case of SCH arising at an uncommon site, the distal femur with radiological local invasion, but without histological pleomorphism and mitosis. It is important to avoid misdiagnosis as these lesions are considered to be benign, non-neoplastic reactive vascular proliferations, with high incidence of recurrence.

Graft-versus-host disease-associated angiomatosis: A clinicopathologically distinct entity

Chronic graft-versus-host disease (GVHD) may present with various cutaneous manifestations. Isolated case reports describe eruptive angiomas in this setting. We sought to provide a clinical and pathologic description of vascular proliferations in patients with GVHD. Cases of documented GVHD associated with vascular proliferations were collected from the National Institutes of Health, Ohio State University, and MD Anderson Cancer Center. Eleven patients with a diagnosis of GVHD who developed vascular proliferations were identified. All patients manifested sclerotic type chronic GVHD of the skin. Vascular lesions were first documented a median of 44 months after transplantation and occurred primarily on the lower extremities or trunk. Histopathology revealed anastomosing networks of thin-walled vascular proliferations in a vague lobular growth pattern, with overlying epidermal acanthosis, peripheral collarette, ulceration, and disorganized fibroblast-rich and fibrotic stroma. Improvement was noted in 1 patient treated with propranolol and sirolimus and 1 patient with electrocautery. Given the retrospective nature of the study, the overall incidence of vascular lesions in patients with GVHD is unknown. Histopathology was present for review on only 3 of 11 patients. The phenomenon of vascular lesions appears to be relatively specific for sclerotic type chronic GVHD when compared with other fibrosing diseases. We propose the term "graft-versus-host disease-associated angiomatosis" to describe this entity.

Tufted hemangioma: clinical case and literature review.

Tufted hemangiomas are relatively rare benign vascular proliferations that are congenital or appear during the first years of life. Herein we present an additional case of tufted hemangioma that appeared one year after birth and discuss its histopathological criteria and differential diagnosis with malignant vascular proliferations including sarcoma Kaposi, angiosarcoma and kaposiform hemangioendothelioma.

MYC amplification and overexpression in primary cutaneous angiosarcoma: a fluorescence in-situ hybridization and immunohistochemical study

MYC, a proto-oncogene located on chromosome 8q24, is involved in the control of cell proliferation and differentiation. Previous studies have documented high-level MYC gene amplification and MYC overexpression by immunohistochemistry (IHC) in post-irradiation angiosarcomas, but not in primary cutaneous angiosarcoma (AS-C) or in other radiation-associated vascular proliferations, such as atypical vascular lesions. Prompted by our recent finding of MYC amplification in a primary hepatic AS, we analyzed a large number of well-characterized AS-C for MYC amplification and protein overexpression. Formalin-fixed, paraffin-embedded blocks from 38 AS-C were retrieved from our archives and were examined by IHC analysis and fluorescence in-situ hybridization (FISH), using a commercially available antibody and probe. For FISH analysis, the number of copies of MYC was compared with the control gene, CEN8 (MYC/CEN8 ratio). All cases occurred on sun-exposed skin; no patient was known to have a history of therapeutic irradiation. Possible associations between survival and a wide variety of clinicopathological variables were evaluated using the log-rank test. By IHC analysis, MYC overexpression was present in 9/38 (24%) AS-C (2–3+: 6 cases, 16%; 1+: 3 cases, 8%). By FISH analysis, 2/5 (40%) informative cases with 2–3+ immunostaining showed high-level gene amplification. One additional case with 3+ immunostaining showed higher level aneusomy of chromosome 8 (5–8 MYC and CEN8). Two out of fourteen (14%) IHC-negative cases also carried MYC amplification (one high level and one lower level). Low copy number gain of chromosome 8 (3–5 MYC and CEN8) was observed in AS-C with or without MYC expression. MYC amplification and MYC protein overexpression were not correlated with clinical outcome. We have shown, for the first time, MYC gene amplification and protein overexpression in primary (non-radiation-associated) AS of the skin. MYC protein overexpression in cases lacking gene amplification likely reflects other mechanisms of MYC activation. The study of a larger number of AS-C showing MYC amplification may be necessary to determine whether the behavior of such cases differs from their more common non-amplified counterparts.

Multiple cutaneous angiosarcomas after breast conserving surgery and bilateral adjuvant radiotherapy: an unusual case and review of the literature.

Breast angiosarcomas (BAs) are rare but serious events that may arise after radiation exposure. Disease outcome is poor, with high risk of local and distant failure. Recurrences are frequent also after resection with negative margins. The spectrum of vascular proliferations associated with radiotherapy in the setting of breast cancer has expanded, including radiation-associated atypical vascular lesions (AVLs) of the breast skin as a rare, but well-recognized, entity. Although pursuing a benign behavior, AVLs have been regarded as possible precursors of postradiation BAs. We report an unusual case of a 71-year-old woman affected by well-differentiated bilateral cutaneous BA, diagnosed 1.9 years after adjuvant RT for synchronous bilateral breast cancer. Whole-life clinical followup is of crucial importance in breast cancer patients.

Treatment of Pediatric Pyogenic Granulomas Using β‐Adrenergic Receptor Antagonists

Propranolol and timolol are nonselective ß-adrenergic antagonists that induce peripheral vasoconstriction and affect angiogenic cytokines. Oral and topical ß-blocker therapy has become the de facto first-line treatment for complicated infantile hemangiomas because of its superior efficacy and tolerability. Pyogenic granulomas or lobular capillary hemangiomas are common acquired vascular tumors accounting for 0.5% of all skin nodules in children. Although they are benign vascular proliferations, treatment is often sought because of recurrent episodes of bleeding and for cosmetic considerations. Numerous treatment options are available, but recurrence rates are high. Noninvasive methods of treatment are being sought, particularly for young children. Herein we report a series of seven cases of cutaneous and mucosal pyogenic granulomas treated successfully using oral or topical ß-blockers.

Intravascular papillary endothelial hyperplasia: histomorphological and immunohistochemical features

BackgroundIntravascular papillary endothelial hyperplasia (IPEH) is a benign intravascular process with features mimicking other benign and malignant vascular proliferations. IPEH lesions predominate in the head-neck region and the extremities. The characteristic histomorphological feature of IPEH is a papillary structure covered with hyperplastic endothelial cells within the vascular lumen. It is critical that this clinically benign lesion should not be mistaken for well-differentiated vascular tumors. In addition to the characteristic histological features, other useful diagnostic features included the intra-luminal location of the lesion, an intimate association with the organizing thrombus, the absence of necrosis, cellular pleomorphism, and mitotic activity. In addition, immunohistochemistry may indicate the vascular origin and proliferative index. In this study, we evaluated histomorphological and immunohistochemical findings (CD31, CD34, FVIII, type IV collagen, SMA, MSA, CD105, and Ki-67 staining) of ten IPEH cases.MethodsTen IPEH cases were re-examined for a panel of histomorphological and immunohistochemical features. CD31, CD34, FVIII, Type IV collagen, SMA and MSA antibodies utilized for immunohistochemical analysis.The histomorphological and immunohistochemical findings were evaluated by two independent pathologists using light microscopy.ResultsAll ten cases involved intraluminal lesions with characteristic features of IPEH. All ten cases (100%) were stained positive for CD31 and CD34. The degree of staining with FVIII, type IV collagen, SMA, and MSA was variable.ConclusionIn this series of specimens, CD31 and CD34 were the most sensitive markers indicating the vascular origin of the lesion. Staining for the other vascular markers (FVIII, type IV collagen, SMA and MSA) was variable. Different maturation degrees of lesions may account for the variation in immunohistochemical staining. Few previous investigations evaluated a wide range of antigen panels in IPEH sections. In our opinion, the evaluation of immune markers in a larger sample set will reveal new features in the maturity and developmental pathogenesis of vascular lesions and angiogenesis. IPEH is a benign lesion, which must be differentiated from malignant tumors such as angiosarcoma and Kaposi’s sarcoma. Improved definition of IPEH lesions using immunohistochemical markers may enhance the ability to differentiate between various vascular lesions.Virtual slidesThe virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1381849312101856.

Solitary angiokeratoma on palms and soles: A clinicopathological analysis of 21 cases

Angiokeratoma includes a group of unrelated diseases characterized by hyperkeratosis and dilation of vessels in the superficial dermis. In this study, 21 cases of solitary lesions located on palms and soles and histopathologically diagnosed as angiokeratoma were analyzed retrospectively. All lesions presented as red to violet macules or plaques. Histopathologically, all of them showed hyperkeratosis and vascular dilation in the papillary to deep dermis. The elongated vessels were of different sizes and shape, lined by a single layer of endothelial cells. In 13 lesions, the endothelial cells protruded into the lumen, forming a hobnail appearance. Immunohistochemical study showed the endothelial cells were positive for CD31 and CD34, negative for D2-40, and focally positive for Wilms tumor 1 (WT-1) in most cases. Our cases represented a rare type of angiokeratoma located on the palms and soles, in which the focal positivity of WT-1 was different from previously reported vascular proliferations.

Cutaneous Epithelioid Sarcomalike (Pseudomyogenic) Hemangioendothelioma

Epithelioid sarcomalike (pseudomyogenic) hemangioendothelioma (ES-H) is a recently described and little-known vascular neoplasm that frequently presents with dermatologic lesions. Histopathologic characterization includes sheets or fascicles of plump, spindled and epithelioid, rhabdomyoblastlike neoplastic cells involving the dermis and often extending to subcutaneous tissue. Immunohistochemical analysis reveals neoplastic cells that show a constant immunophenotype characterized by immunoreactivity for cytokeratins and endothelial markers. We described the clinical, histopathologic, and immunohistochemical features of 2 cases of cutaneous ES-H. Clinical examination revealed multifocal lesions that consisted of erythematous nodules on the leg and foot in case 1 and small perioral papules in case 2. Neoplastic cells had a rhabdomyoblastic appearance, with large nuclei and ample eosinophilic cytoplasm. Immunohistochemical analysis revealed expression of cytokeratin AE1/AE3, CD31, ERG, and FLI-1, with focal and weak positivity for CAM 5.2 and smooth muscle actin. The nuclei of neoplastic cells showed intact expression of INI-1. This immunoprofile, especially the ERG positivity, demonstrated the endothelial nature of proliferating cells. We recommend adding the low-grade neoplasm ES-H to the large list of cutaneous vascular proliferations. Dermatologists should be aware of this low-grade cutaneous vascular tumor.

Acral hemosideric lymphatic malformation

Cutaneous lymphatic malformations represent a group of heterogeneous diseases caused by developmental defects of lymphatic system. The purpose of this study was to report the clinical, histopathological and immunohistochemical features of a distinctive lymphatic malformation. Twelve patients with similar clinical and histopathological features were included in this study. Immunohistochemical staining of CD31, D2-40, Prox1 and Wilms tumor 1 (WT-1) were performed on all lesions. All cases were either congenital lesions or developed during the first 2 years of life. All presented as red to brown papules or nodules on acral sites. Histopathologically, the lesions consisted of a dermal proliferation of flat or slit-like vessels lined with a single layer of endothelial cells. Hemosiderin or extravascular red blood cells were present in all cases. The constituent vessels expressed CD31, D2-40 and Prox1 and lacked expression of WT-1. On the basis of the clinical, histopathological and immunohistochemical findings, our cases represent a unique type of lymphatic malformation that we believe is distinct from previously reported vascular proliferations. We propose the name of acral hemosideric lymphatic malformation for this entity.

Eruptive Cherry Hemangiomatosis Associated With Multicentric Castleman Disease

Eruptive cherry hemangiomatosis, which involves the sudden onset of multiple small vascular proliferations, has been rarely reported as a heralding sign of multicentric Castleman disease (MCD) and other lymphoproliferative diseases. We report a case wherein the rapid appearance of cherry hemangiomata is the presenting sign of MCD. A 25-year-old man with a 10-year history of benign vascular growths developed 23 cutaneous vascular proliferations and systemic symptoms 5 days prior to presentation. Biopsy of the cutaneous lesions revealed a polypoidal proliferation of vessels consistent with cherry hemangiomata. Laboratory studies disclosed systemic abnormalities, and the findings of a subsequent lymph node biopsy confirmed MCD. Combination chemotherapy was initiated, and the cutaneous proliferations improved in association with the systemic disease. There is a scarcity of literature describing the association between eruptive cherry hemangiomatosis and MCD. The likely underlying mechanism is hypersecretion of vascular endothelial growth factor secondary to an elevated interleukin 6 level. Failure to recognize this association may have led to diagnostic delays. The authors suggest careful evaluation and follow-up of all patients presenting with the sudden onset of cherry hemangiomata, particularly with systemic symptoms, lymphadenopathy, or other benign vascular endothelial growths, for the potential development of MCD and other lymphoproliferative diseases.

Atypical florid vascular proliferation in appendix: a diagnostic dilemma

Vascular abnormality of the intestine is rare, except angiodysplasia. We report on an unusual case of atypical florid vascular proliferations of the appendix. A 41-year old male presented with melena. Adhesioned blood clots in the appendiceal orifice were observed by colonoscopy. He underwent laparoscopic appendectomy. Microscopically, a tiny exophytic polypoid mass was observed. The mass showed pyogenic granuloma-like features in the superficial portion and infiltrative florid vascular proliferations in the deeper portion. Endothelial cells showed minimal nuclear atypia, and mitotic figures were observed infrequently and showed positivity for CD31 and CD34 and negativity for HHV-8. Differential diagnoses include from benign vascular tumor to angiosarcoma or Kaposi’s sarcoma, but this lesion does not fit the description of any defined vascular entity. We diagnosed atypical florid vascular proliferations and the patient has been well during the five-month postoperative follow-up.Virtual SlideThe virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1386921325843104