Primary Myelofibrosis with MPL S505N Mutation: The First Case Reported in Korea

MPL mutation is an important molecular marker in myeloproliferative neoplasms (MPN). Although MPL W515 is a hot spot for missense mutations in MPN, MPL S505 mutations have been reported in both familial and non-familial MPN. A 72-year-old male visited the hospital, complaining mainly of dizziness and epistaxis. Leukocytosis, anemia, thrombocytopenia, tear drop cells, nucleated RBCs, and myeloblasts were observed in both complete blood cell counts and peripheral blood smears. Bone marrow aspiration failed due to dilution with peripheral blood. BM biopsy indicated hypercellular marrow, megakaryocytic proliferation with atypia, and grade 3 reticulin fibrosis. Conventional cytogenetics results were as follows: 46,XY,del(13)(q12q22)[19]/46,XY[1]. Molecular studies did not detect JAK2 V617F, BCR/ABL translocation, JAK2 exon 12, and CALR exon 9 mutations. The MPL S505N mutation was verified by colony PCR and Sanger sequencing following gene cloning. Based on the above findings, a diagnosis of overt primary myelofibrosis (PMF) was indicated. Mutation studies of buccal and T cells were not conducted. Further, family members were not subjected to mutation studies. Therefore, we were unable to determine whether this mutation was familial or non-familial. Six months after the first visit to the hospital, the patient died due to pneumonia and sepsis. Thrombotic symptoms or major bleeding events did not develop during the survival period following diagnosis of PMF. To the best of our knowledge, this may be the first reported case of PMF with the MPL S505N mutation in Korea.

A Case of Anti-reticulin Antibody-positivity in Metachronous Double Primary Cancer

No abstract available.

Myxoid and Sarcomatoid Variants of Adrenocortical Carcinoma: Analysis of Rare Variants in Single Tertiary Care Center

The aim of this study is to describe rare variants of adrenocortical carcinoma (ACC) and to compare the prognosis with that of conventional ACC. We retrospectively reviewed 8 cases of myxoid variant, 1 sarcomatoid variant, and 14 cases of conventional ACC, who underwent surgical resection at the Asan Medical Center between 1996 and 2014. An analysis of the clinicopathological characteristics, including the Weiss score, Ki-67 labeling index, and reticulin framework assessment is presented. The mean age of patients with myxoid/sarcomatoid ACC was 45 years; 4 out of 9 patients were women. Mean primary tumor size was 12.9 cm and the mean weight was 702.4 g. Seven patients presented in an advanced stage (stage III/IV); 8 of these eventually developed distant metastasis. The mean Weiss score was 5.0 points and the Ki-67 labeling index was 15.6%. The extent of myxoid or sarcomatoid change on histological examination ranged from 10% to 75% of the examined tumor areas; reticulin framework alteration was observed in all cases. Four patients showed venous tumor thrombus. Most of the clinicopathological parameters were not significantly different from those of conventional ACC. However, myxoid or sarcomatoid variant (hazard ratios [HR], 3.59; 95% confidence intervals [CI], 1.13–11.38; P = 0.030) and Ki-67 labeling index (HR, 3.97; 95% CI, 1.18–13.41; P = 0.030) were independent predictors of overall survival after adjusting for age and sex. Myxoid or sarcomatoid histological features or an increased Ki-67 labeling index may be associated with poor overall survival in patients with ACC.

WHO Grade IV Gliofibroma: A Grading Label Denoting Malignancy for an Otherwise Commonly Misinterpreted Neoplasm

We report a 50-year-old woman with no relevant clinical history who presented with headache and loss of memory. Magnetic resonance imaging showed a left parieto-temporal mass with annular enhancement after contrast media administration, rendering a radiological diagnosis of high-grade astrocytic neoplasm. Tumour sampling was performed but the patient ultimately died as a result of disease. Microscopically, the lesion had areas of glioblastoma mixed with a benign mesenchymal constituent; the former showed hypercellularity, endothelial proliferation, high mitotic activity and necrosis, while the latter showed fascicles of long spindle cells surrounded by collagen and reticulin fibers. With approximately 40 previously reported cases, gliofibroma is a rare neoplasm defined as either glio-desmoplastic or glial/benign mesenchymal. As shown in our case, its prognosis is apparently determined by the degree of anaplasia of the glial component.

Escore clínico-patológico para predizer o risco de metástases e recorrência local em pacientes com carcinoma cortical adrenal e papel do algoritmo da reticulina na distinção entre adenomas e carcinomas corticais adrenais / Clinicopathological score for predicting the risk of metastases and local recurrence in patients with adrenal cortical carcinoma and role of the reticulin algorithm in distinguishing between adrenal cortical adenomas and carcinomas

INTRODUÇÃO: o padrão-ouro para o diagnóstico histológico dos tumores corticais adrenais (TCAs) e sua diferenciação entre adenomas e carcinomas é o sistema de Weiss, cuja aplicação é limitada pela baixa reprodutibilidade de alguns dos critérios que o compõe. Recentemente foi proposto e validado um algoritmo diagnóstico para os TCAs baseado na integridade do arcabouço de reticulina e da membrana basal. Os carcinomas adrenais são tumores raros e apresentam prognóstico reservado, mesmo nos pacientes com doença aparentemente localizada. Além do estadiamento e da extensão da ressecção cirúrgica, outros dados foram reportados na literatura como tendo importância prognóstica, tais como idade ao diagnóstico, padrão funcional, tamanho tumoral, extensão local do tumor primário e alguns achados histológicos e imuno-histoquímicos, com destaque à taxa mitótica e ao índice de Ki-67. O sistema de Weiss, embora permita o diagnóstico diferencial entre adenomas e carcinomas, não foi testado completamente como uma ferramenta para distinguir os carcinomas com boa evolução clínica daqueles com desfecho desfavorável. OBJETIVOS: o presente estudo teve como objetivo primário construir um nomograma para estimar o risco de metástases e recorrência local em portadores de carcinoma adrenal, a partir de dados clínico-patológicos. O objetivo secundário foi avaliar o desempenho do algoritmo da reticulina no diagnóstico diferencial entre adenomas e carcinomas do córtex adrenal. MÉTODOS: para a construção do nomograma, foram analisados dados clínico-patológicos de 129 portadores de carcinomas adrenais atendidos no Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo entre 1976 e 2010. A avaliação do desempenho do algoritmo da reticulina para o diagnóstico histológico dos TCAs foi feita a partir do exame de 89 lâminas (45 adenomas e 44 carcinomas adrenais)...

INTRODUCTION: The gold standard for the histological diagnosis of adrenal cortical tumors (ACTs) and for the differentiation between adenomas and carcinomas is the Weiss system, whose application is limited by poor reproducibility of some of its criteria. Recently, a diagnostic algorithm for ACT diagnosis based on the integrity of the reticulin network and the basal membrane has been proposed and validated. Adrenal carcinomas are rare tumors and have a poor prognosis, even in patients with apparently localized disease. Besides tumor staging and extent of surgical resection, other data have been reported in the literature as having prognostic importance, such as age at diagnosis, the functional pattern, tumor size, local extension of the primary tumor and some histological and immunohistochemical findings, such as the mitotic rate and the Ki-67 index. The Weiss system, while allowing the differential diagnosis between adrenal cortical adenomas and carcinomas, has not been fully tested as a tool for distinguishing carcinomas with favorable clinical outcome from those with unfavorable outcome. OBJECTIVES: The primary objective of this study was to construct a nomogram for estimating the risk of metastasis and local recurrence in patients with adrenal cortical carcinoma, based on clinical and pathological data. The secondary objective was to evaluate the performance of the reticulina algorithm in the differential diagnosis between adenomas and carcinomas of the adrenal cortex. METHODS: For the construction of the nomogram, clinical and pathological data from 129 patients with adrenal cortical carcinomas treated at the Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo between 1976 and 2010 were analyzed. The evaluation of the performance of the reticulin algorithm for the histological diagnosis of ACTs was made from the examination of 89 slides (45 adenomas and 44 adrenal carcinomas)...

Two Cases of Hepatic Sinusoidal Dilatation Mimicking Hepatic Metastases / 대한소화기학회지

Hepatic sinusoidal dilatation is a rare benign vascular disorder characterized by focal dilatation of the sinusoidal spaces. In most cases, the underlying etiology is unclear but it may be related to the impairment of venous outflow or sinusoidal infiltration by diverse causes. Diagnosing hepatic sinusoidal dilatation based soley on imaging study is not easy since there are no pathognomonic radiologic findings indicative of this condition. Recently, the authors experience two cases of hepatic sinusoidal infiltration. The first patient was a 53-year-old man detected to have multiple hepatic nodules on ultrasonography (US) during a routine medical check-up. The second patient was an 82-year-old woman with abdominal discomfort who was referred from local clinic with high suspicion of hepatic metastases on US. In both cases, CT scan demonstrated multiple nodules with rim enhancement on arterial phase that became iso-dense to adjacent liver parenchyma on delayed phase. On MRI, these nodules showed rim enhancement on arterial phase, had high signal intensity on T2 weighted images, and became iso-intense with partial defect on hepatobiliary phase. Because imaging studies could not exclude the presence of hepatic metastases, liver biopsy was performed and it demonstrated hepatic sinusoidal dilatation with well preserved reticulin fiber without any evidence of malignancy. Herein, we report two cases of idiopathic hepatic sinusoidal dilatation mimicking hepatic metastases.

Correlation of chromosome karyotype with dyshaematopoiesis and reticulin in myelodysplastic syndrome / 中国实验血液学杂志

This study was purposed to explore the correlation of chromosome karyotype with dyshaematopoiesis and reticulin in myelodysplastic syndrome (MDS). The data of 202 MDS patients diagnosed and treated in the First Affiliated Hospital of Zhengzhou University were retrospectively analyzed in term of chromosome karyotype, dyshaematopoiesis and reticulin detection results. The chromosome karyotypes were categorized according to the International Prognostic Scoring System (IPSS). The results showed that there was a positive correlation between chromosome karyotype grading and number of lineages with dyshaematopoiesis (r = 0.443, P < 0.05). The detected rates of multilineage dyshaematopoiesis in patients with good, intermediate and poor chromosome karyotypes were 44.4%, 71.4% and 96.3% respectively. There was a positive correlation between chromosome karyotype grading and reticulin grading (r = 0.451, P < 0.05). The positive rates of reticulin in patients with good grading, intermediate and poor chromosome karyotypes were 36.8%, 64.3% and 92.6% respectively. The detected rate of multilineage dyshaematopoiesis, number of lineages with dyshaematopoiesis, the positive rate of reticulin and reticulin grade in patients with poor karyotypes were higher than those in patients with intermediate or good chromosome karyotypes (separately P < 0.01). The above data in patients with intermediate chromosome karyotypes were higher than those in patients with good chromosome karyotypes (separately P < 0.01). It is concluded that the chromosome karyotype grading positively correlates with the number of lineages with dyshaematopoiesis and reticulin grading. When the chromosome karyotype changed from good to poor, the detected rate of multilineage dyshaematopoiesis, number of lineages with dyshaematopoiesis, positive rate of reticulin and reticulin grading became higher and higher.

Discrepant Results for BRAF V600E Mutation Among Different Specimens in a Case of Hairy Cell Leukemia

No abstract available.

High concentration of reticular fibers in periurethral region of the prostatic urethra from patients with benign prostatic hyperplasia as revealed by stereology / Alta concentración de fibras reticulares en la región periuretral de la uretra prostática de pacientes con hiperplasia prostática benigna revelada por estereología

The goal of this investigation was to analyze and quantify changes of the reticular fibers in the prostatic urethra of patients with benign prostatic hyperplasia (BPH) and compare with a control group. Prostatic urethra tissue samples were obtained from ten patients (age range 65 to 79 years, mean 66) with clinical symptoms of bladder outlet obstruction who had undergone open prostatectomy. The ten control group samples (urethral tissue samples from the transitional zone) were collected from prostates obtained during autopsy of accidental death adults of less than 25 years. The Vv of the reticular fibers was determined with stereologic methods from 25 random fields per sample using the point-count method with a M-42 grid test system. The quantitative data were analyzed using the Kolmogorov-Smirnov and Mann-Whitney U tests. The Vv (mean+/-SD) in the control and BPH groups respectively were: 23.4+/- 1.8 and 30.3 +/- 1.2 (0.001). BPH cause significant increase of reticular fibers in prostatic urethra...

El objetivo de esta investigación fue analizar y cuantificar los cambios de las fibras reticulares en la uretra prostática de pacientes con hiperplasia prostática benigna (HPB) y compararlo con un grupo control. Muestras de tejido de uretra prostática se obtuvieron de diez pacientes (rango de edad 65 a 79 años, media 66) con síntomas clínicos de obstrucción del tracto urinario inferior que se habían sometido a prostatectomía abierta. Las diez muestras del grupo de control (muestras uretrales de tejido de la zona de transición) se obtuvieron de próstatas durante la autopsia de sujetos adultos con muerte accidental menores de 25 años. El Vv de las fibras reticulares se determinó con métodos estereológicos de 25 campos al azar por muestra utilizando el método de valor de conteo con el sistema M-42. Los datos cuantitativos se analizaron mediante la prueba de Kolmogorov-Smirnov y Mann-Whitney U. El Vv (media +/- DE) en el grupo control y BPH, respectivamente, fueron: 23,4 +/- 1,8 y 30,3 +/- 1,2 (0,001). La BPH causó aumento significativo de fibras reticulares en uretra prostática...

Multiple focal nodular hyperplasia, an incidental finding on autopsy.

Focal nodular hyperplasia (FNH) is a benign condition of the liver often discovered incidentally on radiological investigation. Although FNH is a well-described lesion in the literature considerable diagnostic problems regarding this entity still remains. We report a case of multiple FNH in a 23-year-old male patient detected as an incidental finding in autopsy. On gross examination FNH was not suspected because of the multiple lesions and the lack of central scar which is characteristically described in FNH. The diagnosis was established on histopathology after examination of multiple sections of the lesions.

Gliosarcoma with prominent smooth muscle component (gliomyosarcoma): A report of 10 cases.

Background and Aim: Gliosarcoma (GS) is an uncommon malignant tumor of the brain, consisting of malignant glial, usually a glioblastoma (GB), as well as sarcomatous component; the latter is usually in the form of fibrosarcoma. We report a series of 10 GSs with prominent smooth muscle component, which is a rare occurrence. Settings and Design: Out of a series of 225 cases of GB admitted in our hospital, 10 were diagnosed as GS with prominent smooth muscle component, gliomyosarcoma (GMS). Materials and Methods: This is an observational study based on the experience with 225 cases of GB, encountered between 1995 and 2008, in our hospital. The tumors showing prominent spindle cell component were stained with reticulin and 20 with strongly positive reticulin stain were diagnosed as GS. They were further studied by immunohistochemical staining for glial fibrillary acidic protein (GFAP), smooth muscle actin (SMA), desmin and factor VIII antigen. Results: Out of 225 cases of GB, 20 were diagnosed as GS. Ten of these showed prominent smooth muscle component and were diagnosed as GMS. They revealed varying degrees of SMA and factor VIII Ag positivity. In the sarcomatous component, SMA and factor VIII positive cells were seen close to the vessel walls as well as away from them. Conclusion: GMS containing prominent smooth muscle component may not be as rare as has been reported in the literature. Both GS and GMS appear to arise from the vessel wall at least in some cases, suggesting their possible vascular origin.

Autologous peripheral blood stem cell transplantation with high-dose therapy for anaplastic large cell lymphoma with progressive myelofibrosis / 대한내과학회지

Myelofibrosis is a myeloproliferative neoplasm characterized by abnormal bone marrow megakaryocyte proliferation with reticulin and collagen fibrosis, leukoerythroblastosis, anemia, increased level of serum lactate dehydrogenase and splenomegaly. Myelofibrosis associated with malignant lymphoma is rare and survival rates appear to have been poor. Herein, we describe our experience in a patient who remained in complete remission with high-dose therapy (HDT) with autologous peripheral blood stem cell transplantation (PBSCT) for ALK-negative ALCL presenting with rapidly progressing myelofibrosis.

Solitary Cutaneous Myxoma

A solitary cutaneous myxoma, referred to as superficial angiomyxomas, is relatively uncommon benign myxoid soft tissue tumors. The lesion usually present on the head, neck, and trunk of adults as a slowly growing asymptomatic nodule. Herein, we describe a case of a pedunculated solitary cutaneous myxoma arising on the vertex of a 48-year-old man, but with no evidence of Carney syndrome. Histologically, the tumor was composed of vascular, mucinous matrix with a network of fine collagen and reticulin fibers, containing stellate and spindle-shaped fibroblasts. There was no evidence of malignancy

Intracranial Solitary Fibrous Tumor

Solitary fibrous tumor is a spindle cell neoplasm that can arise in any place of the body. Intracranial solitary fibrous tumors are rare. To our knowledge, only 57 cases with intracranial lesion have been reported. In Korea three cases have been reported. Our case was a 23-year-old woman who presented with morning headache. MRI showed a large intra-axial mass involving falx with typically isointense and heterogeneous strong enhancement on T1 weighted image in the right parieto-occipital region. Histologically the tumor showed spindle shaped cells within matrix with thick collagen deposition, hypercellularity, focal necrosis, and pleomorphism. Immunohistochemical study demonstrated diffuse positivity for CD34, Vimentin, Reticulin. In case of the intracranial tumors involving the meninges, we also should consider the solitary fibrous tumor with immunohistochemical staining for accurate diagnosis.

Reduced Intensity Conditioning Regimen Followed by Allogeneic Peripheral Blood Stem Cell Transplantation for Acute Panmyelosis with Myelofibrosis / 대한혈액학회지

A 44-year-old male presented with a month history of exertional dyspnea and dizziness. A peripheral blood smear revealed a pancytopenia with 3% of blasts. We were not able to obtain a bone marrow aspirate, but a biopsy specimen showed hypercellularity, proliferation of trilineage cell lines (panmyelosis) with extensive myelofibrosis, and clusters of immature cells at the paratrabecular area. After remission induction therapy with idarubicin 12mg/m2 (D1-3) and cytosine arabinoside 100mg/m2 (D1-7), the bone marrow blast count was decreased, but the marrow fibrosis and pancytopenia persisted. Peripheral blood stem cell transplantation from his HLA-matched brother was performed after administering fludarabine 30mg/m2 for 5 days and busulfan 3.2mg/kg for 2 days. Early engraftment occurred and the bone marrow reticulin fibrosis disappeared. Full-donor chimerism was demonstrated at day 22 by performing short tandem repeats analysis and this was maintained for 1 year. The patient has survived 20 months after transplantation without any complication.

Reticulin morphometry and collagen fibers optical anisotropy as assessed by image analysis after silver impregnation

A new method for the impregnation of tissue sections with ammoniacal silver carbonate in terms of single-step reaction, no gold toning, no oxidation step and silver impregnation after treatment with pancreatic (alfa)-amylase is described. This method yields silver nanocrystalloids with 18.40 nm in average diameter [16]. Natural carbohydrate radicals probably acting as natural reducing agents for silver are assumed to occur. Despite the fact that the method is not specific, reticulin fibers (type III colagen) were clearly distinguished from other collagen fibers types and easily and accurately segmented by image analysis (IA) systems, when using this procedure. Data from myocardial reticulin fibers are presented. Collagen bundles (type I collagen rich structures) exhibited intense linear dichroism (LD) interms of gray averages measured by IA (non-impregnated, natural, collagen fibers do not show LD) Anomalous dispersion of birefringence was also detected, highlighting typical morphologies, including crimp, which allow us to propose the methodo for molecular order studies and to assess collagen bundles as chiral objects, especially together with LD data.

The Effect of Vascular Endothelial Growth Factor on Vascularization in Porous Polyethylene Orbital Implant (Medpor(R))

PURPOSE: We investigated the effect of VEGF usage and the method of surgery on the vascularization rate of the porous orbital implant (Medpor(R)). METHODS: Thirty six Newzealand white rabbits were randomized into 2 groups according to the method of surgery (evisceration and intrascleral implantation and evisceration and retroscleral implantation). Each group was subdivided into two groups, a group treated with VEGF, and the other without VEGF treatment. The degree of vascularization was observed in the four groups at 1, 2, 4 weeks by using cryofilm transfer kit (Finetec, Tokyo, Japan). The implant was sliced at the equator with cryomicrotome and stained with Hematoxylin and Eosin, Masson's trichrome and reticulin. The sample was observed to assay the degree of fibrovascular ingrowth with light microscope. RESULTS: The group in which VEGF was used and the implant was inserted retrosclerally (n=9) showed significantly higher vascularization rate than the other three groups (P0.05). CONCLUSIONS: After using VEGF or inserting the implant retrosclerally, the vascularization of the implant was significantly incresed.

A Case of Primary Orbital Hemangiopericytoma

Hemangiopericytoma is a rare kind of soft tissue tumor. It usually attacks adults without distinction of sex. In most cases, slowly enlarging mass is a chief complaint of patient and symptoms such as tenderness and pain are rare. It is known to frequently attack the lower extremity, especially thigh, pelvic fossa and retroperitoneum, and in rare cases, trunk and upper extremity. In this paper, we report a 47-ear-old female patient with primary orbital hemangiopericytoma in right upper eyelid. Before operation, we found oval-shaped tumor which had a vivid boundary, from the orbital CT and MRI. During the operation, we found an ovoid mass(about 2.6 X 2 X 1 cm) surrounded by a thin capsule on the upper eyelid medial portion. By H&E stain after operation, we found a "staghorn" configuration- haped blood vessel distribution. In an immunohistochemical stain test using factor VIII-related antigen, this tumor was not originated from endotheliumm, but from vessel. In Gomori's reticulin stain test, we confirmly diagnosed these tumor cells as hemangiopericytoma, since these cells were arranged around the vessel, surrounded by a reticulin fiber. She had no symptom of recurrence after operation. As hemangiopericytoma is not frequently developed in an orbital area, we report this case in this paper.