ABSTRACT
YAP1-TFE3-fused hemangioendothelioma is an extremely rare malignant vascular tumor. We present the largest multi-institutional clinicopathologic study of YAP1-TFE3-fused hemangioendothelioma to date. The 24 cases of YAP1-TFE3-fused hemangioendothelioma showed a female predominance (17 female, 7 male) across a wide age range (20-78 years old, median 44). Tumors were most commonly located in soft tissue (50%), followed by bone (29%), lung (13%), and liver (8%), ranging from 3 to 115 mm in size (median 40 mm). About two-thirds presented with multifocal disease, including 7 cases with distant organ metastasis. Histopathologically, we describe three dominant architectural patterns: solid sheets of coalescing nests, pseudoalveolar and (pseudo)vasoformative pattern, and discohesive strands and clusters of cells set in a myxoid to myxohyaline stroma. These patterns were present in variable proportions across different tumors and often coexisted within the same tumor. The dominant cytomorphology (88%) was large epithelioid cells with abundant, glassy eosinophilic to vacuolated cytoplasm, prominent nucleoli and well-demarcated cell borders. Multinucleated or binucleated cells, prominent admixed erythrocytic and lymphocytic infiltrates, and intratumoral fat were frequently present. Immunohistochemically, ERG, CD31, and TFE3 were consistently expressed, while expression of CD34 (83%) and cytokeratin AE1/AE3 (20%) was variable. CAMTA1 was negative in all but one case. All cases were confirmed by molecular testing to harbor YAP1-TFE3 gene fusions: majority with YAP1 exon 1 fused to TFE3 exon 4 (88%), or less commonly, TFE3 exon 6 (12%). Most patients (88%) were treated with primary surgical resection. Over a follow-up period of 4-360 months (median 36 months) in 17 cases, 35% of patients remained alive without disease, and 47% survived many years with stable, albeit multifocal and/or metastatic disease. Five-year progression-free survival probability was 88%. We propose categorizing YAP1-TFE3-fused hemangioendothelioma as a distinct disease entity given its unique clinical and histopathologic characteristics in comparison to conventional epithelioid hemangioendothelioma.
Subject(s)
Basic Helix-Loop-Helix Leucine Zipper Transcription Factors/genetics , Biomarkers, Tumor/genetics , Gene Fusion , Hemangioendothelioma, Epithelioid/genetics , Hemangioendothelioma/genetics , YAP-Signaling Proteins/genetics , Adult , Aged , Asia , Basic Helix-Loop-Helix Leucine Zipper Transcription Factors/analysis , Biomarkers, Tumor/analysis , Europe , Exons , Female , Genetic Predisposition to Disease , Hemangioendothelioma/chemistry , Hemangioendothelioma/pathology , Hemangioendothelioma/surgery , Hemangioendothelioma, Epithelioid/chemistry , Hemangioendothelioma, Epithelioid/pathology , Hemangioendothelioma, Epithelioid/surgery , Humans , Male , Middle Aged , North America , Phenotype , Progression-Free Survival , Time Factors , Young AdultABSTRACT
Epithelioid hemangioendothelioma (EHE) is a rare vascular endothelial neoplasm with characteristic histology and distinctive fusion genes. Its clinical presentation and outcome are heterogeneous, and the determinants of survival are controversial. In this study, we aimed to identify clinicopathologic prognostic factors of EHE in a retrospective cohort of 62 cases with CAMTA1/TFE3/WWTR1 alterations. The tumors were of the CAMTA1 subtype for 59 cases, TFE3 subtype for 2 cases, and variant WWTR1 subtype (WWTR1-ACTL6A) for 1 case. Twenty-two tumors (35.5%) demonstrated atypical histology, defined by having at least 2 of the following 3 findings: high mitotic activity (>1/2 mm2), high nuclear grade, and coagulative necrosis. During a median follow-up of 34 months, 11 patients (18%) died, and the 5-year overall survival rate was 78.8%. Survival did not correlate with such clinical parameters as age, sex, tumor sites, multifocality, and multiorgan involvement. Conversely, based on both univariate and multivariate analyses, large tumor size (>30 mm) and histologic atypia were significantly associated with a shorter survival. A proposed 3-tiered risk assessment system using these 2 parameters significantly stratified the patients into low-risk, intermediate-risk, and high-risk groups with 5-year overall survival rates of 100%, 81.8%, and 16.9%, respectively (P<0.001). Four tumors (6.4%) expressed synaptophysin, which all belonged to the high-risk group and pursued an aggressive course. The present study demonstrated the independent prognostic significance of large tumor size and atypical histology in EHE, as well as the value of risk stratification using these 2 factors. Moreover, we revealed a small EHE subset with aberrant synaptophysin expression, which may have potential prognostic and diagnostic implications.
Subject(s)
Biomarkers, Tumor/analysis , Hemangioendothelioma, Epithelioid/chemistry , Synaptophysin/analysis , Adolescent , Adult , Aged , Aged, 80 and over , Biomarkers, Tumor/genetics , Female , Hemangioendothelioma, Epithelioid/genetics , Hemangioendothelioma, Epithelioid/mortality , Hemangioendothelioma, Epithelioid/pathology , Humans , Immunohistochemistry , In Situ Hybridization, Fluorescence , Male , Middle Aged , Mitosis , Necrosis , Neoplasm Grading , Predictive Value of Tests , RNA-Seq , Retrospective Studies , Risk Assessment , Risk Factors , Time Factors , Young AdultABSTRACT
Epithelioid hemangioendothelioma (EHE) is a malignant vascular tumor that usually affects the liver, lung, bone and deep soft tissues of the extremities or trunk. To our knowledge, only 3 cases in the parotid gland have been reported to date. We report a case of a 62-year-old woman who presented with a 1-year history of a slow-growing, painless mass over the left mandibular angle. Imaging studies showed a 2cm mass over the left parotid gland with peripheral calcifications. The patient underwent a superficial parotidectomy. Sections displayed neoplastic epithelioid cells with cytoplasmic vacuoles containing erythrocytes, surrounded by a myxohyaline stroma. Immunohistochemistry was positive for CD31, CD34, ERG, and factor VIII, but negative for cytokeratin AE1/AE3, CK7, EMA, SMA, and S100. The findings were those of an EHE involving the parotid gland. This case demonstrates an EHE in a rare location and emphasizes the need to consider this tumor when diagnosing uncommon soft tissue tumors of salivary glands.
Subject(s)
Hemangioendothelioma, Epithelioid/diagnosis , Parotid Neoplasms/diagnosis , Biomarkers, Tumor/analysis , Diagnosis, Differential , Female , Hemangioendothelioma, Epithelioid/chemistry , Hemangioendothelioma, Epithelioid/pathology , Hemangioendothelioma, Epithelioid/surgery , Hemangiosarcoma/diagnosis , Humans , Melanoma/diagnosis , Middle Aged , Neoplasm Proteins/analysis , Parotid Neoplasms/chemistry , Parotid Neoplasms/pathology , Parotid Neoplasms/surgery , Soft Tissue Neoplasms/diagnosis , Tomography, X-Ray ComputedABSTRACT
Pseudomyogenic hemangioendothelioma (PMH) is a rare, mostly indolent, endothelial neoplasm of low-grade malignancy, often mimicking myoid and epithelioid tumors histologically. It is more frequent in young adult males and it usually presents with multiple cutaneous nodules, mostly localized at the extremities. It traverses several tissue planes simultaneously and can involve dermis, subcutis, skeletal muscle, and bone. Histologically, it is characterized by plump spindle cells with eosinophilic cytoplasm, often arranged in fascicles and epithelioid cells with "pseudomyogenic" morphology. Immunohistochemically, PMH is positive for Factor VIII, FLI-1, INI-1, vimentin, MDM2, CDK4, CD31, AE1/AE3, EMA, and P63. The efficacy of treatments is only partially known. Because of the frequent multifocal aspect of PMH, which contraindicates surgery, systemic treatments, such as gemcitabine, sirolimus, and everolimus are used. Based on our observation of multifocal PMH of the foot in a 17-year-old male patient, treated with gemcitabine with complete cutaneous response in a 2-year follow-up, we decided to discuss this rare tumor and underline its progression and therapeutic approaches. Thanks to a correct diagnosis, it is possible to avoid aggressive therapeutic approaches, which would be necessary for nonindolent diseases, such as sarcoma, which often needs amputation.
Subject(s)
Antimetabolites, Antineoplastic/therapeutic use , Deoxycytidine/analogs & derivatives , Hemangioendothelioma, Epithelioid/drug therapy , Soft Tissue Neoplasms/drug therapy , Adolescent , Biomarkers, Tumor/analysis , Biopsy , Deoxycytidine/therapeutic use , Foot , Hemangioendothelioma, Epithelioid/chemistry , Hemangioendothelioma, Epithelioid/pathology , Humans , Immunohistochemistry , Magnetic Resonance Imaging , Male , Soft Tissue Neoplasms/chemistry , Soft Tissue Neoplasms/pathology , Treatment Outcome , GemcitabineSubject(s)
Biopsy, Large-Core Needle , Breast Neoplasms/pathology , Hemangioendothelioma, Epithelioid/pathology , Aged , Biomarkers, Tumor/analysis , Breast Neoplasms/chemistry , Breast Neoplasms/diagnosis , Breast Neoplasms/genetics , Calcium-Binding Proteins/genetics , Female , Hemangioendothelioma, Epithelioid/chemistry , Hemangioendothelioma, Epithelioid/diagnosis , Hemangioendothelioma, Epithelioid/genetics , Hemosiderin/analysis , Humans , Intracellular Signaling Peptides and Proteins/genetics , Neoplasm Proteins/analysis , Neoplasm Proteins/genetics , Oncogene Proteins, Fusion/analysis , Oncogene Proteins, Fusion/genetics , Trans-Activators/genetics , Transcription Factors , Transcriptional Coactivator with PDZ-Binding Motif ProteinsABSTRACT
Accurate diagnosis of cutaneous malignant vascular tumors, including angiosarcoma and epithelioid hemangioendothelioma, is critical for determination of appropriate clinical management and prognosis. Although there have been significant advances in understanding genetic aspects of cutaneous vascular biology, differential diagnosis of malignant vascular tumor involving skin and superficial soft tissue is a frequent source of difficulty. This brief overview highlights the clinicopathologic features of primary and secondary cutaneous angiosarcoma and epithelioid hemangioendothelioma and also provides a short summary of newer molecular data.
Subject(s)
Hemangioendothelioma, Epithelioid/pathology , Hemangiosarcoma/pathology , Skin Neoplasms/pathology , Biomarkers, Tumor/analysis , Diagnosis, Differential , Hemangioendothelioma, Epithelioid/chemistry , Hemangiosarcoma/chemistry , Humans , Skin Neoplasms/chemistryABSTRACT
Pseudomyogenic (epithelioid sarcoma-like) hemangioendothelioma is a distinctive vascular neoplasm of intermediate biological potential with a predilection for young adults and frequent multifocal presentation. Pseudomyogenic hemangioendothelioma is characterized by loose fascicles of plump spindled and epithelioid cells with abundant eosinophilic cytoplasm and coexpression of keratins and endothelial markers. Recently, a SERPINE1-FOSB fusion has been identified as a consistent genetic alteration in pseudomyogenic hemangioendothelioma. FOSB gene fusions have also been reported in a subset of epithelioid hemangiomas. The purpose of this study was to assess the potential diagnostic utility of FOSB immunohistochemistry for pseudomyogenic hemangioendothelioma compared with other endothelial neoplasms and histologic mimics. We evaluated whole-tissue sections from 274 cases including 50 pseudomyogenic hemangioendotheliomas, 84 other vascular tumors (24 epithelioid hemangiomas [including 6 cases with angiolymphoid hyperplasia with eosinophilia histology], 20 epithelioid angiosarcomas, 20 epithelioid hemangioendotheliomas [17 CAMTA1 positive, 2 TFE3 positive], 10 spindle-cell angiosarcomas, and 10 epithelioid angiomatous nodules), and 140 other histologic mimics (20 each epithelioid sarcoma, proliferative fasciitis, nodular fasciitis, cellular benign fibrous histiocytoma, spindle-cell squamous cell carcinoma, spindle-cell rhabdomyosarcoma, and leiomyosarcoma). Immunohistochemistry for FOSB was performed following pressure cooker antigen retrieval using a rabbit monoclonal antibody. Diffuse nuclear immunoreactivity for FOSB (>50% of cells) was observed in 48 of 50 (96%) pseudomyogenic hemangioendotheliomas and 13 of 24 (54%) epithelioid hemangiomas (including all angiolymphoid hyperplasia with eosinophilia type). Both FOSB-negative pseudomyogenic hemangioendothelioma cases were decalcified bone tumors. Only 7 other tumors showed diffuse FOSB expression: 2 proliferative fasciitis, 2 nodular fasciitis, 1 epithelioid angiosarcoma, 1 spindle-cell angiosarcoma, and 1 epithelioid hemangioendothelioma. Of note, the FOSB-positive epithelioid hemangioendothelioma was negative for CAMTA1 and TFE3. Focal weak FOSB staining was observed in a subset of histologic mimics and is therefore not diagnostically meaningful. In conclusion, FOSB is a highly sensitive and diagnostically useful marker for pseudomyogenic hemangioendothelioma. Immunohistochemistry for FOSB may be helpful to distinguish pseudomyogenic hemangioendothelioma from histologic mimics including epithelioid sarcoma and other vascular neoplasms. As expected, a subset of epithelioid hemangiomas expresses FOSB, including angiolymphoid hyperplasia with eosinophilia. Although occasional cases of nodular and proliferative fasciitis are positive for FOSB, distinction between these tumor types and pseudomyogenic hemangioendothelioma is usually straightforward based on morphology and other immunophenotypic findings.
Subject(s)
Biomarkers, Tumor/analysis , Hemangioendothelioma, Epithelioid/chemistry , Proto-Oncogene Proteins c-fos/analysis , Sarcoma/chemistry , Adolescent , Adult , Aged , Biopsy , Child , Diagnosis, Differential , Female , Hemangioendothelioma, Epithelioid/pathology , Humans , Immunohistochemistry , Male , Middle Aged , Predictive Value of Tests , Sarcoma/pathology , Young AdultABSTRACT
OBJECTIVE: To investigate the clinicopathologic characteristics, differential diagnosis and prognosis of pulmonary epithelioid hemangioendotheliomas (PEHs). METHODS: The clinical symptoms and imaging findings of 6 cases of PEHs were investigated and pathologic analyses including histomorphologic and immunohistochemical studies were performed. RESULTS: Clinical symptoms of the patients were nonspecific and insidious. The typical radiological manifestation was characterized by multiple small pulmonary nodules. The pathological findings were well-demarcated hypocellular hyalinized nodules with more cellularity at the periphery of the nodule. The neoplastic cells showed mild nuclear atypia and prominent eosinophilic cytoplasm with vacuoles, attempting to form primitive vasculature. Immunohistochemically, tumor cells were positive to CD31, CD34 and ERG. Follow-up data from 8 months to 5 years showed no tumor progression, except for the development of bone metastases in one case at 6 months. CONCLUSIONS: PEHs are uncommon vascular tumors with low-intermediate malignancy. Using H&E and immunohistochemistry, the final pathological diagnosis can be made and misdiagnosed as a benign fibrotic nodule or other malignant tumors can be avoided. The most effective treatment is surgical resection, if necessary, combined with chemotherapy or radiotherapy.
Subject(s)
Hemangioendothelioma, Epithelioid/pathology , Lung Neoplasms/pathology , Vascular Neoplasms/pathology , Adult , Bone Neoplasms/secondary , Diagnosis, Differential , Female , Hemangioendothelioma, Epithelioid/chemistry , Hemangioendothelioma, Epithelioid/diagnostic imaging , Hemangioendothelioma, Epithelioid/secondary , Humans , Immunohistochemistry , Lung Neoplasms/chemistry , Lung Neoplasms/diagnostic imaging , Male , Middle Aged , Prognosis , Treatment Outcome , Vascular Neoplasms/chemistry , Vascular Neoplasms/diagnostic imagingSubject(s)
Hemangioendothelioma, Epithelioid/pathology , Lip Neoplasms/pathology , Sarcoma/pathology , Skin Neoplasms/pathology , Adult , Biomarkers, Tumor/analysis , Biopsy , Chin , Hemangioendothelioma, Epithelioid/chemistry , Hemangioendothelioma, Epithelioid/surgery , Humans , Immunohistochemistry , Lip Neoplasms/chemistry , Lip Neoplasms/surgery , Male , Sarcoma/chemistry , Sarcoma/surgery , Skin Neoplasms/chemistry , Skin Neoplasms/surgeryABSTRACT
Epithelioid sarcoma-like hemangioendothelioma is a rare vascular neoplasm that usually occurs in the distal extremities of young adults. Although the overall behavior of this neoplasm is usually indolent with a low risk of distant metastasis, the risk of local recurrence is significant. Therefore, initial surgical treatment with an adequate margin is important to improve the prognosis. However, epithelioid sarcoma-like hemangioendothelioma is frequently misdiagnosed. A preoperative misdiagnosis could result in resection without a sufficient margin. Herein, we describe a 68-year-old man with epithelioid sarcoma-like hemangioendothelioma on the chest wall, which was treated by wide resection despite difficulties with the preoperative diagnosis.
Subject(s)
Hemangioendothelioma, Epithelioid/pathology , Sarcoma/pathology , Thoracic Neoplasms/pathology , Aged , Biomarkers, Tumor/analysis , Biopsy , Diagnosis, Differential , Hemangioendothelioma, Epithelioid/chemistry , Hemangioendothelioma, Epithelioid/surgery , Humans , Immunohistochemistry , Male , Margins of Excision , Positron Emission Tomography Computed Tomography , Predictive Value of Tests , Sarcoma/chemistry , Sarcoma/surgery , Thoracic Neoplasms/chemistry , Thoracic Neoplasms/surgery , Treatment OutcomeABSTRACT
Epithelioid hemangioendothelioma (EHE) is a malignant endothelial neoplasm characterized by recurrent translocations involving chromosomal regions 1p36.3 and 3q25, resulting in the formation of a WWTR1-CAMTA1 fusion gene in approximately 90% of cases; a small subset (<5%) have a YAP1-TFE3 fusion gene. The WWTR1-CAMTA1 fusion gene leads to overexpression of both genes. WWTR1 protein is expressed in many different cell types, whereas CAMTA1 expression is normally limited to the brain. A prior study using a polyclonal antibody directed against regions within the C-terminus of CAMTA1 reported widespread expression in both normal tissues and diverse tumor types. In contrast, a recent study using a different polyclonal antibody directed against the C-terminus of CAMTA1 suggested that this other antibody is a potentially useful diagnostic marker for EHE. Our study aimed to validate this finding in a large series of EHE cases and to determine whether CAMTA1 is expressed in other epithelioid mesenchymal tumors that may mimic EHE. Protein expression of CAMTA1 was evaluated in whole-tissue sections of 204 tumors using a polyclonal anti-CAMTA1 antibody: 59 EHE (48 conventional, 11 "malignant"; 4 with known TFE3 gene rearrangement); 70 other epithelioid vascular tumors; and 75 nonendothelial epithelioid mesenchymal neoplasms. In total, 51/59 cases (86%) of EHE showed diffuse nuclear staining for CAMTA1, including 44/48 cases (92%) with conventional histology and 7/11 cases (64%) with "malignant" histology. Of the 8 CAMTA1-negative tumors, 6 were positive for TFE3. With the exception of 1 case previously diagnosed as epithelioid angiosarcoma on core biopsy, all other tumor types examined were negative for CAMTA1. In conclusion, in keeping with the reported frequency of WWTR1-CAMTA1 in EHE, nuclear CAMTA1 expression is identified in the majority of EHE cases, whereas other epithelioid mesenchymal neoplasms are negative for CAMTA1. These findings support the diagnostic utility of immunohistochemistry for CAMTA1 in distinguishing EHE from histologic mimics, in particular benign epithelioid vascular tumors, epithelioid angiosarcoma, and epithelioid sarcoma, an important distinction given the differences in biological potential and clinical course.
Subject(s)
Biomarkers, Tumor/analysis , Calcium-Binding Proteins/analysis , Cell Nucleus/chemistry , Hemangioendothelioma, Epithelioid/chemistry , Immunohistochemistry , Trans-Activators/analysis , Biopsy , Cell Nucleus/pathology , Diagnosis, Differential , Hemangioendothelioma, Epithelioid/pathology , Humans , Predictive Value of TestsABSTRACT
We report a case of a 76-year-old female with multiple lung nodules (Fig. 1 Rx). Pathologic evaluation of the lower left video-assisted thoracoscopic surgery (VATS) lobectomy VATS-lobectomy showed four nodules that were described as pulmonary epithelioid hemangio-endothelioma (PEH); the immunohistochemical stains showed that the neoplastic cells expressed CD31, a variable expression for factor VIII and a low expression of CD34. In the remaining parenchyma of the lobe, multiple nests of neuroendocrine cells were observed with immunohistochemical confirmation, and the diagnosis was diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH). To our knowledge, the association between PEH and DIPNECH has never been described in the literature.
Subject(s)
Hemangioendothelioma, Epithelioid/pathology , Lung Neoplasms/pathology , Multiple Pulmonary Nodules/pathology , Neuroendocrine Cells/pathology , Precancerous Conditions/pathology , Aged , Biomarkers, Tumor/analysis , Biopsy , Female , Hemangioendothelioma, Epithelioid/chemistry , Hemangioendothelioma, Epithelioid/diagnostic imaging , Hemangioendothelioma, Epithelioid/surgery , Humans , Hyperplasia , Immunohistochemistry , Lung Neoplasms/chemistry , Lung Neoplasms/diagnostic imaging , Lung Neoplasms/surgery , Multiple Pulmonary Nodules/chemistry , Multiple Pulmonary Nodules/diagnostic imaging , Multiple Pulmonary Nodules/surgery , Neuroendocrine Cells/chemistry , Pneumonectomy/methods , Precancerous Conditions/chemistry , Precancerous Conditions/diagnostic imaging , Precancerous Conditions/surgery , Predictive Value of Tests , Thoracic Surgery, Video-Assisted , Tomography, X-Ray Computed , Treatment OutcomeABSTRACT
A right atrial mass excised from the heart of a 53-year-old man was incidentally found to be an epithelioid hemangioendothelioma (EHE). EHE is a rare malignant tumor with marked variability in clinical outcomes. Cardiac involvement is unusual but does occur [Bisesi MA, Broderick LS, Smith JA. MR demonstration of right atrial involvement in multifocal epithelioid hemangioendothelioma. AJR Am J Roentgenol 1996;167(4):953-4; Di Biasi P, Scrofani R, Santoli C. Cardiac hemangioendothelioma. Ann Thorac Surg 1995;59(3):792-3], and the prognostic is usually considered relatively good after resection. However, the tumor in this case shows atypical features, which raises concerns. In addition to complete en bloc resection, a close follow-up is considered mandatory.
Subject(s)
Heart Neoplasms/surgery , Hemangioendothelioma, Epithelioid/surgery , Biomarkers, Tumor/analysis , Biopsy , Echocardiography, Transesophageal , Heart Atria/pathology , Heart Atria/surgery , Heart Neoplasms/chemistry , Heart Neoplasms/pathology , Hemangioendothelioma, Epithelioid/chemistry , Hemangioendothelioma, Epithelioid/pathology , Humans , Immunohistochemistry , Incidental Findings , Male , Middle Aged , Predictive Value of Tests , Tomography, X-Ray Computed , Treatment OutcomeABSTRACT
Epithelioid hemangioendothelioma (EHAE) is a malignant vascular tumor derived from endothelial cell often misdiagnosed as Hepatic carcinoma on the basis of radiological features. Till now etiology of this rare curiosity is unknown but it is related with use of oral contraceptives pills (OCP), liver trauma, exposure to vinyl chloride and hepatitis. We herein report on a case which failed to be diagnosed by cytopathology, computed tomography (CT) and magnetic resonance imaging (MRI). Patient was a 46 yr old man presented with abdominal distension for a month. Initial liver function test (LFT) was increased whereas renal function test (RFT) and alpha-fetoprotein (AFP) were normal. His abdominal ultrasound revealed multiple hypoechoic nodules and multiple liver calcifications. Subsequently laparoscopic omental biopsy and Ultrasound guided liver biopsy was done showing the neoplastic cells scattered in fibrous stroma. The immunohistochemistry for endothelial tumor cells stained positive for Vimentin (+++), CD10 (+++), CD34 (++), CD31 (+), Factor VIII antigen (focal) (+) and low proliferative activity for ki-67. Our case is very interesting in which patient admitted with nonspecific symptoms of abdominal pain and diagnosed to be a Malignant Hepatic EHAE metastasized to the peritoneum, omentum and mesentery. The patient was on thalidomide 50 mg/day and increased to 100 mg/day. 5-Flurouracil (FU) intraperitoneal chemotherapy and other symptomatic and supportive treatment was given to the patient. Our case highlights on the importance of immunohistopathological diagnosis, compare the radiological findings of this disease and discuss the treatment strategy with review of available literature.
Subject(s)
Hemangioendothelioma, Epithelioid/secondary , Liver Neoplasms/pathology , Mesentery/pathology , Omentum/pathology , Peritoneal Neoplasms/secondary , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Biomarkers, Tumor/analysis , Biopsy , Diagnosis, Differential , Fluorouracil/therapeutic use , Hemangioendothelioma, Epithelioid/chemistry , Hemangioendothelioma, Epithelioid/therapy , Humans , Immunohistochemistry , Liver Neoplasms/chemistry , Liver Neoplasms/therapy , Male , Mesentery/chemistry , Middle Aged , Omentum/chemistry , Peritoneal Neoplasms/chemistry , Peritoneal Neoplasms/therapy , Predictive Value of Tests , Thalidomide/therapeutic use , Tomography, X-Ray Computed , Treatment OutcomeABSTRACT
Hepatic epithelioid hemangioendothelioma is a rare vascular neoplasm with an unpredictable malignant potential. Different therapeutic options are available, depending on the basis of disease extension and the patient's overall condition. A correct pathological diagnosis is necessary and is often based on scant material. Here, we report a case diagnosed on fine needle aspiration and on a small surgical biopsy. In addition, we will review the literature. The patient is a 54-year-old woman who presented with persistent pain in the right hypochondrium and suffered from weight loss. Ultrasound examination and CT scan showed several focal and confluent hepatic lesions. Thus, an ultrasound-guided fine-needle aspiration (US-FNA) was performed. A cytological diagnosis of vascular proliferation with epithelioid component was performed. Afterwards, a hepatic "small biopsy" (SB) was made. Histological and immunohistochemical data were consistent with a hepatic epithelioid hemangioendothelioma diagnosis. The patient, however, is in good general condition and is waiting for a hepatic transplantation; repeated total CT scan showed no signs of metastasis. The literature was reviewed in order to define the pathological features that were helpful in the cytological and histological diagnosis of hepatic epithelioid hemangioendothelioma, and to better understand if pathological data is prognostically useful.
Subject(s)
Hemangioendothelioma, Epithelioid/pathology , Liver Neoplasms/pathology , Biomarkers, Tumor/analysis , Biopsy , Diagnostic Errors , Endoscopic Ultrasound-Guided Fine Needle Aspiration , Female , Hemangioendothelioma, Epithelioid/chemistry , Hemangioendothelioma, Epithelioid/surgery , Humans , Immunohistochemistry , Liver Neoplasms/chemistry , Liver Neoplasms/surgery , Liver Transplantation , Middle Aged , Positron-Emission Tomography , Predictive Value of Tests , Tomography, X-Ray Computed , Waiting ListsABSTRACT
Epithelioid hemangioendothelioma (EHE) is a rare tumor of the urinary system. Only three cases of EHE of the bladder have been reported to date, and the biological properties of the tumor in this location remain poorly characterized. We report a case of primary EHE of the urinary bladder in a 58-year-old woman who was treated by transurethral resection and review the existing literature on the diagnosis and treatment of EHE of the bladder.
Subject(s)
Hemangioendothelioma, Epithelioid , Urinary Bladder Neoplasms , Biomarkers, Tumor/analysis , Biopsy , Cystectomy , Female , Hemangioendothelioma, Epithelioid/chemistry , Hemangioendothelioma, Epithelioid/pathology , Hemangioendothelioma, Epithelioid/surgery , Humans , Immunohistochemistry , Middle Aged , Tomography, X-Ray Computed , Treatment Outcome , Urinary Bladder Neoplasms/chemistry , Urinary Bladder Neoplasms/pathology , Urinary Bladder Neoplasms/surgeryABSTRACT
AIM: To investigate the indications and outcomes of liver transplantation for hepatic epithelioid hemangioendothelioma (HEHE). METHODS: Between 1989 and August 2013, in the Department of General, Transplant, and Liver Surgery, Medical University of Warsaw, 1306 orthotopic liver transplantations (OLTx) were performed, including 72 retransplantations. Unresectable HEHE was an indication for OLTx in 10 patients (0.8% of primary OLTx), the mean age of the patients was 40.5 ± 13.3 years (range 23-65 years), and the male-to-female ratio was 2:8. Kaplan-Meier survival analysis in HEHE, hepatocellular carcinoma (HCC), and other OLTx recipients groups was performed. The differences in mortality were compared using the χ(2) test. A P-value < 0.05 indicated statistical significance. RESULTS: No concomitant liver disease was found in any patient. There was no neoadjuvant chemotherapy or radiotherapy. Liver function test results were normal in most of the patients. The levels of alpha-fetoprotein, carcinoembryonic antigen, and carbohydrate antigen 19-9 were normal. In immunohistochemical staining, the neoplastic cells were positive for factor VIII-related antigen, CD31, and CD34, which are endothelial cell markers, and negative for cytokeratin 19, cytokeratin 7, and HepPar-1. Nine patients were alive without tumor recurrence. One patient died 2 mo after OLTx due to septic complications. No morbidity was observed. Maximum follow-up was 11.4 years, with a minimum of 1 mo. The cumulative survival rate at the end of follow-up in HEHE patients was 87.5% compared with 54.3% in the HCC group and 76.3% in the other OLTx recipients group (χ(2) test = 1.784, df = 2, P = 0.409). CONCLUSION: Unresectable HEHE, without extrahepatic metastases is an excellent indication for liver transplantation. Long-term survival is very good and much better than in HCC patients and the entire group of OLTx patients.
Subject(s)
Hemangioendothelioma, Epithelioid/surgery , Liver Neoplasms/surgery , Liver Transplantation , Adult , Aged , Biomarkers, Tumor/analysis , Chi-Square Distribution , Female , Hemangioendothelioma, Epithelioid/chemistry , Hemangioendothelioma, Epithelioid/mortality , Hemangioendothelioma, Epithelioid/pathology , Humans , Immunohistochemistry , Kaplan-Meier Estimate , Liver Function Tests , Liver Neoplasms/chemistry , Liver Neoplasms/mortality , Liver Neoplasms/pathology , Liver Transplantation/adverse effects , Liver Transplantation/mortality , Male , Middle Aged , Poland , Predictive Value of Tests , Reoperation , Retrospective Studies , Risk Factors , Time Factors , Treatment Outcome , Young AdultABSTRACT
Epithelioid hemangioendothelioma (EH) is a rare tumor arising from the vascular endothelial cells of soft tissue or visceral organs. The most common visceral site is the liver, where it is often involved in a multifocal manner known as hepatic EH (HEH). Surgical resection with curative intent represents the gold standard therapy. When surgery is not feasible, or in cases of metastatic disease, no standard medical treatment is currently indicated. In small series, drugs with anti-angiogenic activity (such as bevacizumab, sorafenib, thalidomide, and lenalidomide) have been proposed with promising results. We describe a 73-year-old man with multifocal non-resectable HEH treated with lenalidomide. Disease status was evaluated by abdominal ultrasound and magnetic resonance every four months. The patient was treated for a total of 39 mo with prolonged disease stabilization and, at the time of writing, is still under treatment with a good tolerance profile. During a short period of treatment discontinuation, the disease showed slight progression that immediately resolved after the reintroduction of lenalidomide. Lenalidomide may represent a valid treatment option for HEH due to its anti-angiogenic and antineoplastic activities. This preliminary result merits further study in a large series.
Subject(s)
Angiogenesis Inhibitors/therapeutic use , Hemangioendothelioma, Epithelioid/blood supply , Hemangioendothelioma, Epithelioid/drug therapy , Liver Neoplasms/blood supply , Liver Neoplasms/drug therapy , Thalidomide/analogs & derivatives , Aged , Antigens, CD34/analysis , Biomarkers, Tumor/analysis , Biopsy , Hemangioendothelioma, Epithelioid/chemistry , Hemangioendothelioma, Epithelioid/pathology , Humans , Immunohistochemistry , Lenalidomide , Liver Neoplasms/chemistry , Liver Neoplasms/pathology , Magnetic Resonance Imaging , Male , Thalidomide/therapeutic use , Time Factors , Treatment OutcomeABSTRACT
Although benign hemangiomas are among the most common diagnoses amid connective tissue tumors, sarcomas showing endothelial differentiation (ie, angiosarcoma and epithelioid hemangioendothelioma) represent under 1% of all sarcoma diagnoses, and thus it is likely that fewer than 500 people in the United States are affected each year. Differential diagnosis of malignant vascular tumors can be often quite challenging, either at the low end of the spectrum, distinguishing an epithelioid hemangioendothelioma from an epithelioid hemangioma, or at the high-grade end of the spectrum, between an angiosarcoma and a malignant epithelioid hemangioendothelioma. Within this differential diagnosis both clinico-radiological features (ie, size and multifocality) and immunohistochemical markers (ie, expression of endothelial markers) are often similar and cannot distinguish between benign and malignant vascular lesions. Molecular ancillary tests have long been needed for a more objective diagnosis and classification of malignant vascular tumors, particularly within the epithelioid phenotype. As significant advances have been recently made in understanding the genetic signatures of vascular tumors, this review will take the opportunity to provide a detailed update on these findings. Specifically, this article will focus on the following aspects: (1) pathological and molecular features of epithelioid hemangioendothelioma, including the more common WWTR1-CAMTA1 fusion, as well as the recently described YAP1-TFE3 fusion, identified in a morphological variant of epithelioid hemangioendothelioma; (2) discuss the heterogeneity of angiosarcoma clinical, morphological and genetic spectrum, with particular emphasis of MYC and FLT4 gene amplification in radiation-induced angiosarcoma; and (3) provide a practical guide in the differential diagnosis of epithelioid vascular tumors using molecular testing.
Subject(s)
Hemangioendothelioma, Epithelioid , Hemangiosarcoma , Biomarkers, Tumor/analysis , Biomarkers, Tumor/genetics , Diagnosis, Differential , Genetic Predisposition to Disease , Hemangioendothelioma, Epithelioid/chemistry , Hemangioendothelioma, Epithelioid/genetics , Hemangioendothelioma, Epithelioid/pathology , Hemangiosarcoma/chemistry , Hemangiosarcoma/genetics , Hemangiosarcoma/pathology , Humans , Phenotype , Predictive Value of Tests , PrognosisABSTRACT
We present a case of a 58-year-old female with a rare vascular tumor of intermediate malignancy. The initial manifestation was a pseudoaneurysm caused by the rupture of the right pulmonary artery after tumor invasion. The diagnosis of epithelioid hemangioendothelioma was confirmed by the morphologic and immunocytochemical features after surgery. The patient recovered smoothly and there has been no evidence of local recurrence or metastasis during the 2 years of follow-up.