Prominent Vascular Proliferation Research Articles

Mediastinal high-grade vasculogenic mesenchymal tumour with seminoma: a case report and literature review

Germ cell tumours with somatic-type solid malignancy (GCT-STM) are a rare disease of the mediastinum. Recently, a cohort of vasculogenic mesenchymal tumour (VMT)-nonseminoma cases with different prognoses were recognized and reported. Here, we report a case of mediastinal high-grade VMT with a seminoma. A 16-year-old male had a fever, chest tightness and fatigue. Chest CT showed a 7.5 cm×5.3 cm solid mass in the right anterior mediastinum. The serum levels of alpha-fetoprotein (AFP), beta-human chorionic gonadotropin (β-HCG) and carcinoembryonic antigen (CEA) were within the normal range. Tumorectomy was performed. The tumour was irregular, and no capsule was found. The cut surface was greyish white and greyish brown with medium consistency. There were foci of bleeding and necrosis. Microscopic histology showed prominent vascular proliferation, which was lined by mildly atypical endothelial cells in a cellular stroma with significant cytologic atypia. The vascular spectrum varied from crevice-like or antler-like thin- to thick-walled vessels. Beyond the tumour area, inside the remnant thymus tissues, there were small clusters of polygonal tumour cells with clear cytoplasm, distinct cell membranes, and round to polygonal nuclei with prominent nucleoli that were positive for Oct4, PLAP, SALL4 and CD117. The patient did not receive any treatments pre- or postoperation, and his condition was stable without progression after 14 months of follow-up evaluation. Here, we added a new entity of GCT-STM of the mediastinum composed of VMT and seminoma. A better understanding of the pathological features of GCT-VMT could help pathologists improve their awareness of these rare diseases.

Treatment of bisphosphonate induced osteonecrosis of jaw in rats using an angiogenesis factor (A-Heal) and ABMDO (Autologous Bone Marrow Derived Osteoblasts)

Background and objectiveThe aims of this study were to create Bisphonates Related Osteonecrosis of the Jaw (BRONJ) in rats and treat them with an angiogenesis factor (A-Heal) and ABMDO (Autologous Bone Marrow Derived Osteoblasts). Materials and methodsThirty female Wistar rats were procured. Rats were labeled as Group I to III. Group I = Osteoblast group, Group II = A-Heal and Group III Control group. In Groups I-III, BRONJ was created and treated in Group I with ABMDO, Group II with A-Heal and Group III was the control group. At the end of the four weeks post treatment, all the animals were humanely killed. The intact maxillae were removed in total. Histopathological and radiological examinations were carried out with physicians blinded to the groups. ResultsComputerized tomography revealed that Groups I and II demonstrated the presence of dense osteosclerosis, intralesional calcifications, and adequate healing of the overlying soft tissues compared to Group III, which showed the presence of bone erosions at the alveolar ridge with a lack of intralesional calcifications and ulceration of the overlying soft tissues. Histologically, H&E staining Group 1 and Group 2 both showed marked reactive bone formation. Group 2 additionally revealed the most prominent vascular proliferation (also highlighted by Factor VIII, an endothelial cell marker) among all groups. Group 3 showed cartilaginous proliferation with less reactive bone formation, implicating decreased endochondral ossification compared to Groups 1 and 2. ConclusionThis study shows that angiogenesis factor (A-Heal) and ABMDO were successful in the treatment of experimentally created BRONJ in an animal model.

Erythema ab igne with features resembling keratosis lichenoides chronica

Erythema ab igne (EAI) is an asymptomatic dermatosis that develops in response to chronic exposure to low-grade heat. Characteristic findings on histopathology include epidermal atrophy, dermal elastosis, atypical histiocytes, and melanin and hemosiderin deposition. Reactive endothelial changes and prominent vascular proliferation are variable. Keratosis lichenoides chronica (KLC) is a rare lichenoid hyperkeratotic dermatosis. Acanthosis with parakeratosis and a lichenoid interface dermatitis with lymphocytes, histiocytes, and plasma cells are characteristic findings of KLC. Although its etiology remains unclear, KLC has been reported to occur in response to heat. Herein, we report a case of EAI with features resembling KLC.

2571 Unicentric Castleman Disease as a Cause of Ileal Perforation: A Case Report

INTRODUCTION: Castleman disease is describes a group of heterogenous lymphoproliferative disorders that share histopathologic features. It is divided into Unicentric castleman disease (UCD) and Multicentric Castleman disease. We present a case of a patient with one year history of recurrent small bowel obstruction (SBO), which was found to be due to UCD affecting the mesentery. CASE DESCRIPTION/METHODS: A 75 years old gentleman initially presented one year ago with an episode of SBO. He had no history of abdominal or pelvic surgery. CT scan showed a transition point near the terminal ileum and mesenteric/retroperitoneal lymphadenopathy. Patient underwent a colonoscopy which showed a stenotic ileocecal valve with active colitis in the terminal ileum and ascending colon suggestive of resolving intestinal ischemia. This time, patient was admitted with decreased oral intake due to SBO. He was found to have a low albumin of 0.8 and an AKI on CKD. He also had bilateral pleural effusions and new ascites. He was treated conservatively initially, but he developed new abdominal pain with X ray showing free air under the diaphragm concerning for intestinal perforation. Patient underwent emergent laparotomy, where he had a perforated terminal ileum and multiple large fibrotic lymph nodes in the associated mesentery. Pathology showed proliferation of atretic follicles. There were occasional penetrating capillaries and the mantle lymphocytes have an onion-skin pattern. The interfollicular zones showed increased plasma cells, but not prominent vascular proliferation. CD3 and CD20 stains showed an intact immune-architecture. The overall findings showed a mixed pattern of Castleman lymphadenopathy, with some features of both the hyaline vascular and plasma cell variants. He had IgA of 510 mg/dl and an abnormal SPEP with IgG lambda paraprotein of 0.39 g/dl. His hospital course was complicated by septic shock due to bacterial and fungal peritonitis. Patient eventually went into cardiac arrest and died. DISCUSSION: Mixed variant CD is mostly multicentric, however, some patients with UCD reveal features of both hyaline vascular type and plasma cell type. In this case, apart from abdominal pain and recurrent SBO episodes, there were no other complaints. Acute phase reactants, CBC, and serological testing for HIV, HHV-8, Hepatitis B, Hepatitis C, RPR and PPD were all unremarkable. UCD is usually asymptomatic and generally curable using surgical resection but in this case led to severe complication ending in patient's demise.

Classical Hodgkin Lymphoma With Aberrant CD8 Expression: A Clinicopathologic Study of Five Cases.

Hodgkin/Reed-Sternberg (HRS) cells of classical Hodgkin lymphoma (CHL) are of B-cell origin. In a small number of CHL cases, the tumor cells can express T-cell antigens. CD8 expression in this setting is extremely rare. We identified 5 cases of CHL with aberrant CD8 expression from our database. The patients included 3 men and 2 women with a median age of 33 years (range = 20-59 years). All the patients initially presented with lymphadenopathy and variable number of RS cells. Two cases were classified as mixed cellularity type that showed prominent vascular proliferation mimicking peripheral T-cell lymphoma. Two cases represented nodular sclerosis type. The tumor cells in all cases were positive for CD8 and negative for CD2, CD3, CD4, and CD7 and carried germline T-cell receptor genes. Molecular studies revealed T-cell receptor genes to be in germline configuration in 4 cases with available information. Given the morphologic overlap with peripheral T-cell lymphoma and the rarity of this type of CHL, identifying more cases will help our better understanding of this entity.

Clinical Findings and Explant Liver Histology in Crigler Najjar Disease

Introduction We evaluated pediatric patients with Crigler Najjar disease who received LT at our center. Materials and Methods We reviewed the clinical and laboratory data of patients with Crigler Najjar disease who received LT at Başkent University from 2001-2017. Histopathologic examinations of explanted livers were also recorded. Results There was total of 7 patients (5 female 71.4%). The mean age at the time of LT was 5±7.1 years (range: 0.2-17.5 y). The liver function tests before LT were: total bilirubin: 31.28±7.3 mg/dL (range: 20.7-43.3 mg/dL), direct bilirubin: 1.39±1.19 mg/dL (range: 0.46-3.93 mg/dL), AST: 174±330 mg/dL (range: 24-922 IU/L), ALT: 79±88 mg/dL (range: 19-276 IU/L), GGT: 67±53 mg/dL (range: 27-184 U/L), ALP: 569±327 mg/dL (range: 115-1055 IU/L). Patients were given 11±3 hours (range: 8-16 hours) phototherapy (6/7 patients), phenobarbital (5/7 patients), cholestyramine (3/7 patients) before LT. Plasmapheresis was used in 1 patient to decrease bilirubin levels before LT. The mean body weight of the patients at the time of transplant was 20.9±19.6 kg (range: 6.7-58 kg). The donor was father in 5 and mother in 2 LT. Left lateral lobe was used in 5, left lobe was used in 1 and right lobe was used in 1 patient. Patients were followed up for 5.83±4.3 years (range: 1-11.5 y). Postoperative complications included hepatic artery thrombosis in 2 patients, hepatic vein thrombosis in 1, bile leak in 2, acute cellular rejection in 2, pneumothorax in 1, primary graft dysfunction and cholestasis in 1. One patient had neurologic sequela and died after vomiting and aspiration during his sleep at 1 year posttransplant. One patient has mild mental retardation. Other patients are alive with normal developmental milestones. One patient had cirrhosis and homozygous mutation in UGT1A1 gene consistent with Crigler Najjar type 1. She was only given ursodeoxycholic acid and cholestyramine as treatment before liver transplant. She is doing fine without any neurologic deficit after LT. Explanted livers showed normal structure in all patients except one. 5 patients had mild hepatocanalicular cholestasis, cirrhotic patient additionally had dilated bile ducts filled with cholestatic plugs and prominent ductular and vascular proliferation. 1 patient without cirrhosis had mild portoportal fibrosis, as well as mild bile ductular proliferation. 5 patients had lymphomononuclear inflammation in the portal areas. 3 patients showed ballooning degeneration in the hepatocytes.3 patients had neutrophilic infiltration in the paranchyme and subcapsular areas. 1 patient had diffuse microvesicular steatosis. Conclusions Severe form of Crigler Najjar disease can be successfully cured by LT. Mild increase in liver function tests other than bilirubin may be recorded before surgery. Histopathological explants may show cholestatic changes and portal/paranchymal inflammation. This finding may be secondary to co-existing liver diseases or Crigler Najjar disease itself.

Generalized retiform purpura as a presenting sign of diffuse dermal angiomatosis

A 49-year-old man presented with progressive, painful, ulcerative, retiform purpuric patches on the torso and extremities. Multiple skin biopsies revealed a prominent pan-dermal vascular proliferation but no occlusive vasculopathy or cutaneous vasculitis. Diffuse dermal angiomatosis should be considered in the differential diagnosis of retiform purpura, especially in patients with atherosclerotic disease or underlying hypercoagulable states.

Histiocytic Infiltrate in Angioimmunoblastic T-Cell Lymphoma with Cutaneous Nodules and Progressive Ulceration: A Rare Manifestation

Dear Editor: Angioimmunoblastic T-cell lymphoma (AITL) is an aggressive non-Hodgkin's nodal peripheral T-cell lymphoma that accounts for 18% of peripheral T-cell lymphoma, and cutaneous AITL has not been well characterized in terms of clinical and histopathologic features1. Because AITL is usually diagnosed based on lymph node biopsy, it is difficult for physicians to diagnose cutaneous AITL without lymphadenopathy. Eighty-four years old female visited our hospital with nodules on both calves. The patient claimed that she had first noticed tender nodules several months prior to the visit and that they have gradually increased in size (Fig. 1A). Examination results indicated skin-colored palpable hard nodules with tenderness, about 3.0×3.0 cm in size. The nodule histologically revealed prominent vascular proliferation surrounded by abundant epitheloid histiocytes and lymphocytes without prominent nuclear atypia in the dermis (Fig. 2A, B). There were many positive cells in CD3 and CD68 (Fig. 2C, D), foci of small aggregates of positive cells in CD31, and negative cells in S100 protein, CD1a and Epstein-Barr virus (EBV). T-cell receptor-γ gene rearrangement was found to be monoclonal. In suspicion of cutaneous T-cell lymphoma, she underwent further evaluation, such as laboratory test, whole-body computed tomography (CT), and positron emission tomography-CT in hemato-oncology. On a follow-up visit, the nodule on her left calf became a progressive ulcer with a granulation-like base (Fig. 1B). However, we could not find any evidence of infection. Inguinal lymphadenopathy was identified from imaging study, and lymph node biopsy was performed (Fig. 2F, G). Many cells in the lymph node showed positive reactions for CD3, CD4, CD5, CD21 and programmed death-1 (PD-1) (Fig. 2H~L), but negative reactions for CD8, CD20 and EBV. An additional stain for PD-1 of the skin was also positive (Fig. 2E). Based on these immunohistological findings, we were able to diagnose the skin lesion as AITL. After 6 months, she developed aggressive malignant lymphadenopathy in multiple regions of the body. Fig. 1 (A) Localized hard subcutaneous nodules about 3.0×3.0 cm in size with no epidermal changes were palpable on both calves. (B) After several weeks, the nodule on the left calf developed into a progressive ulcer covered with granulation-like tissues, ... Fig. 2 (A~E) Histopathological findings of skin biopsy. (A) Dense inflammatory cell infiltration into the deep dermis (H&E, ×40). (B) Numerous small to medium-sized vascular channels surrounded by densely mixed inflammatory cells, especially ... Skin involvement occurs in up to 50% of AITL patients and presents with nonspecific maculopapular eruption in most cases, but less commonly in patients with nodules1. Our patient first presented with cutaneous nodules, and histologically showed vascular proliferation with abundant histiocytic infiltration. Progressive ulceration made AITL diagnose more difficult until the lymph node biopsy result was obtained. However, PD-1 staining for the lymph node and the skin was useful in making the diagnosis2. Until now, predominant histiocytic infiltrate in cutaneous AITL such as our case has not been described. Only a few AITL cases have been reported with nodular lesion histologically showing presence of histiocytes. Although histiocytes' role in cutaneous lymphoma has been described in prominent granulomatous reaction, most cases were of mycosis fungoides3 and rare cases of AITL. CD68 has been known as negative prognostic marker for lymphoma-associated macrophage in follicular lymphoma4 and classic Hodgkin's lymphoma5. In our opinion, abundant histiocytic infiltration in cutaneous AITL may be associated with the cutaneous nodules and also with the progressive ulcer, and histiocytes might play a more aggressive role in the clinical features of AITL, which will be evaluated in the future.

Dermal Spindle Cell Adenolipoma

Dermal Spindle Cell Adenolipoma

Glioblastoma blood flow measured with stable xenon CT indicates tumor necrosis, vascularity, and brain invasion

Tumor vasculature is a promising therapeutic target in glioblastoma. Imaging tumor blood flow may help assess the efficacy of anti-angiogenic treatments. We determined the clinical usefulness of stable xenon CT performed preoperatively in patients with glioblastoma. This is a prospective cohort study. We determined absolute tumor blood flow before surgery in 38 patients with glioblastoma using stable xenon CT. We also histologically examined tumor specimens obtained from surgery and quantified their vascularity (by CD31 and CD105 immunostain), necrosis (by hematoxylin and eosin stain), and the presence of neuronal processes (by neurofilament immunostain). According to the xenon CT blood flow map, there are 3 types of glioblastoma. Type I glioblastomas have unimodal high blood flow histograms; histologically there is little necrosis and vascular proliferation. Type II glioblastomas have unimodal low blood flow histograms; histologically there is prominent necrosis and vascular proliferation. We propose that in type II glioblastoma, the abnormal vessels induced by hypoxia are inefficient at promoting blood flow. Type III glioblastomas have multimodal blood flow histograms. Histologically there is significant neuronal tissue within the tumor. Patients with type III glioblastomas were more likely to develop a post-surgical deficit, consistent with the inclusion of normal tissue within the tumor. Preoperative measurement of absolute blood flow with stable xenon CT in patients with glioblastoma predicts key biological features of the tumor and may aid surgical planning.

Cutaneous bacillary angiomatosis in renal transplant recipients: report of three new cases and literature review

Bacillary angiomatosis (BA) is a rare vasculoproliferative disorder due to Bartonella henselae (BH) or Bartonella quintana. It can involve many organs, including the skin, and has been mainly reported in patients with acquired immunodeficiency syndrome. In organ transplant recipients (OTR), this disorder remains misdiagnosed and therapeutic guidelines are nonexistent. We report 3 cases of BA with skin involvement in OTR and review similar cases from the literature. BA manifests on the skin with violaceous lesions mimicking Kaposi sarcoma, and is associated with fever, lymphadenopathy, and liver, spleen, or lung nodules. Bartonellosis infections in OTR are due to BH, the agent causing cat-scratch disease (CSD), but BA comprises histologically a prominent vascular proliferation, which is usually lacking in CSD. Cultures and serologic tests are poorly reliable for the diagnosis, which relies on demonstration of BH within the lesions. A history of cat exposure exists in most cases and pediatric OTR are at higher risk. Prevention consists of regular use of a flea-control product in cats and prompt cleaning of scratches. Our cases highlight several original features of this rare condition, which could potentially improve the management of BA in OTR.

Longitudinal brain imaging of five malignant glioma patients treated with bevacizumab using susceptibility-weighted magnetic resonance imaging at 7 T

Malignant glioma is a rare tumor type characterized by prominent vascular proliferation. Antiangiogenic therapy with the monoclonal antibody bevacizumab is considered as a promising therapeutic strategy, although the effect on tumor vascularization is unclear. High-field susceptibility-weighted imaging (SWI) visualizes the microvasculature and may contribute to the investigation of antiangiogenic therapy responses in gliomas. We prospectively studied five adult malignant glioma patients treated with bevacizumab-containing regimens. In each patient, we performed three 7-T SWI and T1-weighted imaging investigations (baseline and 2 and 4 weeks after the start of bevacizumab treatment). In addition, we imaged a postmortem brain of a patient with glioblastoma using 7-T SWI and performed detailed histopathological analysis. We observed almost total resolution of brain edema in three of five patients after initiation of bevacizumab therapy. In one case with rapid increase of the lesion size despite bevacizumab therapy, SWI showed progressive increase of irregular hypointense structures, most likely corresponding to increasing amounts of pathological microvasculature. In one case with progressive neurological decline, 7-T images showed multiple intratumoral microhemorrhages after the first bevacizumab application. Correlation of postmortem neuroimaging with histopathology confirmed that SWI-positive structures correspond to tumor vasculature. The experience from our case series indicates that longitudinal 7-T SWI seems to be an appropriate method for investigation of changes in brain tumor vascularization over time under antiangiogenic therapy.

Leigh's Disease: The Acute Clinical Course of a Two-Year-Old Child with Subacute Necrotizing Encephalomyelopathy

We report the untypical clinical course of a previously healthy two-year-old girl, who died suddenly and unexpectedly after an episode of vomiting. At forensic autopsy no other pathological findings could be diagnosed than multiple reddish, sunken areas in brain stem, mesencephalon, and pons. Histologically they presented as areas of spongiosis of the neuropil with prominent endothelial hyperplasia and vascular proliferation whereas nerve cells were well preserved. On the basis of the characteristic neuropathological findings in combination with the age of the child, we had to take into consideration that the child might have died from subacute necrotizing encephalomyelopathy (Leigh's Disease) despite the untypical, fulminant clinical course.

Diabetic Striatal Disease: Clinical Presentation, Neuroimaging, and Pathology

Unilateral movement disorders and contralateral neuroimaging abnormalities of the striatum have been sporadically reported as a rare syndrome associated with diabetes mellitus. Despite characteristic imaging findings and clinical manifestations, the mechanism underlying this syndrome is still unclear. Six patients with this syndrome were studied clinically and subjected to MRI neuroimaging; one underwent biopsy of the striatum, and another underwent additional MR spectroscopy at 3.0T and FDG-PET. Neuroimaging findings were characterized by a T1-hyperintense unilateral lesion restricted to the striatum, contralateral to the symptomatic limbs. The biopsied striatum contained patchy necrotic tissue, severe thickening of all layers of arterioles, and marked narrowing of vessel lumens. Hyaline degeneration of the arteriolar walls, extravasation of erythrocytes, and prominent capillary proliferation were also notable, together with lymphocytic infiltration and macrophage invasion. In one patient, PET examination revealed decreased accumulation of FDG in the lesion. The MR spectrum for the diseased striatum revealed a decrease in the NAA/Cr ratio (1.35), normal Cho/Cr ratio (1.22), and a peak for myoinositol, while the spectrum on the contralateral site revealed a decrease in the NAA/Cr ratio (1.48), increase in Cho/Cr (1.32), but no peak for myoinositol. The constellation of signs and symptoms and neuroimaging characteristics in previous reports and the six additional cases described here with neuropathological data and findings of MR spectroscopy appears unique enough to be termed "diabetic striatopathy." This syndrome appears in poorly controlled diabetics due to obliterative vasculopathy with prominent vascular proliferation, vulnerability to which is restricted to the striatum.

Massive Localized Lymphedema With Unusual Presentations: Report of 2 Cases and Review of the Literature

Massive localized lymphedema is a benign soft tissue lesion that usually presents as a large mass in morbidly obese adults. The diagnosis may be challenging as it can mimic other lesions, including well-differentiated liposarcoma. We report 2 cases of massive localized lymphedema with unusual presentation. The first case is a recurrent massive localized lymphedema in the right thigh of a 40-year-old morbidly obese woman. In addition to typical massive localized lymphedema features such as prominent edema and vascular proliferation in the adipose tissue, we observed prominent and abundant multinucleated stromal floret-like giant cells, arborizing network of capillaries, and areas of hyalinized collagen. Our second case is in a rare location (scrotum extending into penile soft tissue) in an overweight 55-year-old male. This lesion exhibits striking smooth muscle hyperplasia. Lack of staining by antibodies against murine double minute 2 protein and cyclin dependent kinase 4 and absence of high mobility group AT- hook 2 transcription factor rearrangement by fluorescence in situ hybridization support our diagnosis of massive localized lymphedema in both cases.

Vascular Changes in Merkel Cell Carcinoma Based on a Histopathological Study of 92 Cases

Although prominent vascular proliferation is a known feature of various neuroendocrine tumors, it has not been systematically studied in Merkel cell carcinoma (MCC) of the skin. The purpose of this study was to fully characterize the light microscopic, immunohistochemical, and ultrastructural features of vascular changes associated with MCC and to determine their frequency and differential diagnostic implications. Additionally, the presence of human herpesvirus 8 DNA in the lesional tissue was investigated. Of 92 studied cases of MCC, 18 cases (20%) were found to exhibit foci of prominent vascular changes which were classified into the following 6 patterns: pericyte hyperplasia, pyogenic granuloma-like, hemangioendothelioma-like, epithelioid hemangioma-like, peliosis-like, and follicular dendritic cell tumor-like pattern. In addition, Azzopardi phenomenon was observed. These changes occurred singly or in combination. Human herpesvirus 8 DNA was identified by polymerase chain reaction in none of the 18 cases. It is concluded that prominent vascular proliferations may be seen in 20% of MCC, and thereby, MCC resembles neuroendocrine tumors in other organs. When unduly prominent and encountered in a limited biopsy specimen, vascular alterations may represent a potential diagnostic pitfall, but, on the other hand, they themselves may serve as a clue to the correct diagnosis. Human herpesvirus 8 does not play a role in angiogenesis in MCC.

Central neurocytoma: A clinical, radiological and pathological study of nine cases

Purpose Central neurocytoma is a rare intraventricular brain tumor that affects young adults and presents with increased intracranial pressure secondary to obstructive hydrocephalus. Typically, it has a favorable prognosis after adequate surgical intervention, but in some cases the clinical course is more aggressive. In this report, we describe the diagnosis and treatment of central neurocytoma in a series of patients at our institution. Patients and methods Our series of nine patients (M:F = 2:7, mean age, 28.2 years) with ventricular tumors showed typical radiological, histologic and immunohistochemical features of central neurocytoma. Most patients received craniotomy with removal of the tumor through transcallosal or transcortical approach. The surgical and histopathologic data of these patients were reviewed and analyzed. Results The prognosis is generally favorable. Although most patients were alive and well at the last follow-up, two developed recurrence. Typical histologic features of recurrent neurocytoma include high proliferative activity (MIB-1 labeling index: 2.0–6.8%), prominent vascular proliferation and remarkable synaptophysin expression. Two patients (non-recurrent) died during follow-up due to sepsis or central failure. The MIB-1 labeling indices were as high as 2.2–5.4% for these two patients. Conclusion Although central neurocytoma is generally a benign neoplasm, some variant forms of recurrence are also present. Complete resection provides favorable long-term prognosis in most cases. Recurrent tumors are often local and the patients seem to recover well after a second resection followed by radiotherapy. Histologic features such as tumor proliferation (MIB-1 labeling index), vascular proliferation, and synaptophysin expression are often prominent in the recurrent tumor. We recommend that these histologic features be considered for tumor recurrence during treatment and follow-up of these patients.

Prominent vascular endothelial proliferation in clinically aggressive neuroblastoma

10611 Background: Tumor blood vessels are disorganized and vascular endothelial cell proliferation (VEP) has been identified as a poor prognosticator in many adult cancers. To determine the clinical significance of VEP in neuroblastoma (NB), we evaluated blood vessel architecture in tumor sections from 51 children diagnosed at Children's Memorial Hospital, Chicago (CMH) and in 154 NB tumors on a Tissue Microarray (TMA) constructed at Children's Hospital of Philadelphia (CHOP). Methods: H&E-stained tumor sections were examined for the presence of structurally abnormal vessels and further characterized by immunostaining with anti-CD31 and von Willebrand factor (vWF) antibody to highlight endothelial cells. Tumors that contained vessels with disorganized walls and more than one endothelial cell layer were classified as VEP positive. Tumor sections that contained only thin walled vessels with no more than one layer of endothelial cells were classified as VEP negative. Associations between VEP and established clinico-pathologic features and outcome were assessed. Results: In the CHOP series, VEP was associated with high-risk group classification and MYCN amplification (p<0.001 and p=0.006). In the CMH series only 5 of the 10 children with MYCN amplification had VEP but 4 of these 5 patients have died, while there were no deaths in the subset of patients with MYCN amplified tumors that lacked VEP (n=5). In both study groups, VEP was significantly associated with Schwannian stroma-poor histology (CMH series: p=0.008; CHOP series: p<0.001) and decreased survival probability (CMH series: p=0.017; CHOP series: p= 0.014). Conclusions: The association between structurally abnormal vessels and poor outcome provides further support for the concept that angiogenesis plays an important role in determining the biologic behavior of NB tumors. Our results also indicate that angiogenesis is regulated differently in Schwannian stroma-rich versus stroma-poor NB tumors. Further studies investigating the activity of angiogenic inhibitors in children with clinically aggressive stroma-poor NB are warranted. No significant financial relationships to disclose.

Ultrasound guided fine needle aspiration biopsy of parathyroid gland and lesions

BackgroundParathyroid gland and their tumors comprise a small proportion of non-palpable neck masses that are investigated by ultrasound (US) guided fine needle aspiration biopsy. We reviewed our institution's cases of US guided FNAB of parathyroid gland and their lesions to determine the role of cytology for the preoperative diagnosis of parathyroid gland and their lesions.MethodAll cases of FNAB of parathyroid gland and lesions in the last 10 years were reviewed in detail with respect to clinical history and correlated with the histopathologic findings in available cases. The cytologic parameters that were evaluated included cellularity assessed semiquantitatively as scant, intermediate or abundant (<50, 51–500 or >500 cells), cellular distribution (loose clusters, single cells/naked nuclei, rounded clusters, two- and three-dimensional clusters, and presence of prominent vascular proliferation), cellular characteristics (cell size, nuclear shape, presence/absence of a nucleolus, degree of mitosis, amount of cytoplasm, and appearance of nuclear chromatin), and background (colloid-like material and macrophages). Immunostaining for parathyroid hormone (PTH) was performed on selected cases using either destained Pap smears or cell block sections.ResultsTwenty cases of US-guided FNAB of parathyroid glands and their lesions including 13 in the expected locations in the neck, 3 in intrathyroid region, 3 in thyroid bed, and 1 metastatic to liver were studied. Majority of the cases showed intermediate cellularity (51–500 cells) with round to oval cells that exhibited a stippled nuclear chromatin, without significant pleomorphism or mitotic activity. The cells were arranged in loose two dimensional groups with many single cells/naked nuclei around the groups. Occasionally macrophages and colloid like material was also encountered. There was no significant difference in the cytomorphologic features between normal gland, hyperplasia adenoma, or carcinoma. Immunocytochemical analysis for PHT was performed for 14 cases (6 destained smears and 8 cell blocks) which showed distinct cytoplasmic positivity.ConclusionUS-guided FNAB is a useful test for confirming the diagnosis of not only clinically suspected parathyroid gland and lesions but also for detecting parathyroid glands in unexpected locations such as in thyroid bed or within the thyroid gland. Although there is significant overlap in the cytomorphologic features of cells derived from parathyroid and thyroid gland, the presence of stippled nuclear chromatin, prominent vascular proliferation with attached epithelial cells, and frequent occurrence of single cells/naked nuclei are useful clues that favor parathyroid origin. Distinction of the different parathyroid lesions including hyperplasia, adenoma, and carcinoma cannot be made solely on cytology. Immunostaining for PTH can be performed on destained Pap smears and cell block sections which can be valuable for confirming parathyroid origin of the cells.

Lhermitte-Duclos Disease: A Report of 31 Cases with Immunohistochemical Analysis of the PTEN/AKT/mTOR Pathway

Lhermitte-Duclos disease (LDD) is a rare cerebellar tumor associated with Cowden disease (CD) and germline mutations in the PTEN gene. To further define these relationships, we reviewed clinical and pathologic findings in 31 LDD cases and analyzed the status of the PTEN pathway in 11 of them. We hypothesized that the granule cell hypertrophy in LDD is secondary to activation of mammalian target of rapamycin (mTOR), a downstream effector in the PTEN/AKT pathway and a major regulator of cell growth. Histopathologically, in addition to the classical findings of LDD, we observed prominent vascular proliferation and vacuolization of the white matter in many of the lesions. Four patients met diagnostic criteria for CD, and many of the remaining patients had some clinical features of CD. Immunohistochemical analysis showed high levels of phospho-AKT and phospho-S6 in the large ganglionic cells forming the lesions, indicating activation of the PTEN/AKT/mTOR pathway and suggesting a central role for mTOR in the pathogenesis of LDD. These data support recommendations for genetic testing and screening for CD in patients with LDD and suggest a novel therapy for LDD through pharmacologic inhibition of mTOR.