Primary pulmonary epithelioid hemangioendothelioma metastatic to the pleura and mediastinal lymph node with a prominent rhabdoid cytomorphology showing CAMTA1::WWTR1 fusion and novel PRDM1 and TNFRSF14 mutations.

Cases of epithelioid hemangioendothelioma with WWTR1::CAMTA1 fusion can show rhabdoid cytomorphology. Lack of intracytoplasmic luminal spaces, marked rhabdoid cytomorphology, and variability in the expression of vascular markers makes the diagnosis of EHE challenging. Therefore, a high level of suspicion and ancillary studies (immunohistochemistry and next generation sequencing) help reach a definitive diagnosis in these cases.

NR1D1::MAML1 epithelioid and spindle cell sarcoma mimicking pseudomyogenic hemangioendothelioma in core biopsy: A case report and review of the literature.

Epithelioid and spindle cell sarcomas with NR1D1::MAML1/2 gene fusions are rare and emerging entities. Only six cases of NR1D1-rearranged mesenchymal tumors have previously been reported in the literature; they are often characterized by an epithelioid morphology, at least focal pseudogland formation, prominent cytoplasmic vacuoles, and focal to diffuse immunohistochemical expression of keratin. We herein report the first case of an NR1D1::MAML1 epithelioid and spindle cell sarcoma with dual immunohistochemical expression of ERG and FOSB, mimicking a pseudomyogenic hemangioendothelioma (PHE) on core biopsy. The sarcoma arose in the left forearm of a 64-year-old man. Initial biopsy showed a mesenchymal neoplasm composed of epithelioid and spindle cells dispersed in myxoid stroma with scattered stromal neutrophils. The morphologic features, combined with the dual immunohistochemical expression of ERG and FOSB, initially mimicked PHE, representing an important potential diagnostic pitfall. The patient subsequently underwent a radical resection, which showed a much more diffuse epithelioid appearance with nested architecture and pseudogland formation. Next-generation sequencing was performed on the resection specimen, which revealed an NR1D1::MAML1 gene fusion, confirming the final diagnosis. Given the fully malignant potential of this tumor, knowledge and recognition of this rare entity are essential to ensure proper management, prevent misdiagnosis, and further characterize the clinical course of this emerging entity. Comprehensive molecular testing can help to identify these rare tumors and exclude the possibility of epithelioid mimics, including PHE.

[MRI manifestations of 40 cases with the hepatic epithelioid hemangioendothelioma classification based on the morphology and size].

Objective: To explore the MRI characteristics of the hepatic epithelioid hemangioendothelioma (HEHE) classification according to morphology and size. Methods: The clinical, pathological, and MRI imaging data of 40 cases with HEHE confirmed pathologically from December 2009 to September 2021 were retrospectively analyzed. A paired sample t-test was used for comparison between the two groups. Results: There were 40 cases (5 solitary, 24 multifocal, 9 local fusion, and 2 diffuse fusion) and 214 lesions (163 nodules, 31 masses, and 20 fusion foci). The most common features of lesions were subcapsular growth and capsular depression. The signal intensity of lesions ≤1cm was usually uniform with whole or ring enhancement. Nodules and mass-like lesions ≥1cm on a T1-weighted image had slightly reduced signal intensity or manifested as a halo sign. Target signs on a T2-weighted image were characterized by: target or centripetal enhancement; fusion-type lesions; irregular growth and hepatic capsular retraction, with ring or target-like enhancement in the early stage of fusion and patchy irregular enhancement in the late stage; blood vessels traversing or accompanied by malformed blood vessels; focal bleeding; an increasing proportion of extrahepatic metastases and abnormal liver function with the type of classified manifestation; primarily portal vein branches traversing; and reduced overall intralesional bleeding rate (17%). Lollipop signs were presented in 19 cases, with a high expression rate in mass-type lesions (42%). The fusion lesions were expressed, but the morphological manifestation was atypical. The diffusion-weighted imaging mostly showed high signal or target-like high signal. An average apparent diffusion coefficient of lesions was (1.56±0.36) ×10(-3)mm(2)/s, which was statistically significantly different compared with that of adjacent normal liver parenchyma (t=8.28, P<0.001). Conclusion: The MRI manifestations for the HEHE classification are closely related to the morphology and size of the lesions and have certain differences and characteristics that are helpful for the diagnosis of the disease when combined with clinical and laboratory examinations.

New Molecular Insights, and the Role of Systemic Therapies and Collaboration for Treatment of Epithelioid Hemangioendothelioma (EHE).

OPINION STATEMENT: Epithelioid hemangioendothelioma (EHE) is an ultra-rare, translocated vascular sarcoma. EHE can have different clinical presentations from indolent to rapidly evolving cases, behaving as a high-grade sarcoma. Serosal effusion and systemic symptoms such as fever and severe pain are known as adverse prognostic factors; however, outcome prediction at disease onset remains a major challenge. In spite of its rarity, an international collaborative effort is in place with the support of patient advocates to increase the knowledge of EHE biology, develop new treatment options, and improve patient access to new active medications. Currently, systemic therapies are indicated only for patients suffering from progressive and/or symptomatic disease and in patients with a high risk of organ dysfunction. Standard systemic agents available so far for treatment of sarcomas, and in particular anthracycline-based chemotherapy, have marginal activity in EHE. On this background, EHE patients should be always considered for clinical study when available. The MEK inhibitor trametinib has been recently investigated prospectively in advanced EHE showing some activity, but the publication of the full dataset is still awaited to better interpret the results. Besides, there are data on response to antiangiogenics such as sorafenib and bevacizumab and, from retrospective studies, interferon, thalidomide, and sirolimus. Unfortunately, none of these agents is formally approved for EHE patients and access to treatments varies greatly between countries causing a huge disparity in patient care from one country to another.

A Case Presentation of Metastatic Hepatic Epithelioid Hemangioendothelioma: A Rare Vascular Tumor.

Epithelioid hemangioendothelioma (EHE) is an uncommon vascular tumor that can present in various organs, including the liver. Hepatic EHE (HEHE) may showcase with metastases at initial presentation, as patients have vague symptoms such as right upper quadrant pain leading to the risk of delayed diagnosis. There is no standard treatment. Fortunately, prognosis is good. This remains true for some patients with metastatic disease who are not being actively treated. In this report, we present a unique case of metastatic HEHE in a 65-year-old Caucasian male who has not received treatment and continues to remain in stable condition after his initial diagnosis three years ago.

Epithelioid Vascular Lesions: The Differential Diagnosis and Approach in Cytology and Small Biopsies.

Vascular neoplasms are rare tumors with a multitude of clinical presentations and behavior, which make accurate identification and subclassification challenging on limited small biopsies. Within the spectrum of these lesions, the ones with epithelioid morphology, such as epithelioid hemangioendothelioma and epithelioid angiosarcoma, are particularly challenging given the morphologic overlap with nonvascular lesions and the limited cells due to hemodilution on sampling. Herein, we review the differential diagnosis of epithelioid vascular neoplasms, with a focus on the cytomorphology, differential diagnoses, and ancillary studies that pathologists should be aware of when evaluating small biopsies and aspirates, including novel translocations, and associated monoclonal immunohistochemistry antibodies, that can help in the diagnosis of some of these tumors. Awareness of these morphologic and ancillary study findings in these rare tumors will hopefully allow pathologists to recognize and render-specific diagnoses on limited samples of these challenging lesions.

Rare case of epithelioid hemangioendothelioma in the right innominate vein-An innovative diagnostic approach.

BACKGROUND AND AIMS: Epithelioid hemangioendothelioma is a rare malignant vascular tumor with limited literature. AIMS: We reported an innovative endovascular biopsy of the right innominate vein tumor. MATERIALS AND METHODS: Endovascular suction thrombectomy was performed with multipurpose catheter and constant negative pressure under fluoroscopic guidance. RESULTS: Epithelioid hemangioendothelioma was diagnosed preoperatively and a complete margin-free tumor resection with patch repair of the right innominate vein was achieved via sternotomy. DISCUSSION: Preoperatively diagnosis is usually not available due to lesions' location. Identifying malignant vascular tumors becomes valuable to guide the surgical treatment. CONCLUSIONS: In this case report, this innovative endovascular approach led to a rare preoperative diagnosis of EHE and subsequent margin-free resection.

Two years progression-free survival under vinorelbine metronomic therapy of a patient with metastatic epithelioid hemangioendothelioma.

Epithelioid hemangioendothelioma (EHE) is a very rare vascular tumor, originating from endothelial cells. The etiology of EHE is unknown, yet at the molecular level, different angiogenic stimulators may act as promoters of endothelial cell proliferation. The tumor affects more commonly the lung, the liver and the bones but it can affect any other organ. Due to its heterogeneous presentation and its rarity it is often misdiagnosed. No treatment is proved to be efficient in metastatic EHE and the median survival of patients with metastatic pleural disease is generally poor, less than one year. we report a case of a 57-year-old female with multiple metastatic EHE including pleural, diagnosed by medical thoracoscopy, with a progression-free survival of 24 months with oral vinorelbine as maintenance therapy after combination of cisplatin-vinorelbine. We believe that this therapy might be of value to test in this patient population as it has never been tested before.

A case of pseudomyogenic hemangioendothelioma misdiagnosed as low-grade malignant fibrous histiocytoma and review of literature. / è¯¯è¯Šä¸ºä½Žåº¦æ¶æ€§çº¤ç»´ç»„ç»‡ç»†èƒžç˜¤çš„å‡è‚Œæºæ€§è¡€ç®¡å† çš®ç˜¤1ä¾‹å¹¶æ–‡çŒ®å¤ä¹ .

Pseudomyogenic hemangioendothelioma (PHE) is a rare angiogenic tumor. Histologically, the morphological characteristics of neoplastic vessels and endothelial differentiation are not obvious, and it is easy to be confused with epithelioid sarcoma, epithelioid hemangioendothelioma and myogenic tumor. PHE usually occurs in arms and legs in young people and has a significant male predominance. The tumor has a predilection for the distal extremities and its typical manifestation is multiple center invasion of a single limb, which can involve all layers of skin and subcutaneous tissues,and is often accompanied by abvious pain. Histologically, PHE is characterized by infiltrative growth of tumor. Most tumor lesions are composed of sheets and loose fascicles of plump spindle or epithelioid cells within a background of variably prominent inflammatory infiltration, which was commonly composed of neutrophils. Some cells may resemble rhabdomyoblasts, and nuclear atypia and mitosis were rare. The tumor cells generally expressed positive cytokeratin (CK), ETS-related gene (ERG), Friend leukemia virus integration 1 (FLI1) and integrase interactor 1(INI1). In some cases, the tumor cells expressed CD31. A case of a young woman was reported in this paper, who presented with a subcutaneous mass with severe pain and was chronologically misdiagnosed with herpes zoster, low-grade malignant fibrous histiocytoma and epithelioid hemangioendothelioma. In this study, the clinical and pathological features, differential diagnosis and the latest progress in therapy of PHE were analyzed based on relevant literature.

Loss of expression of YAP1 C-terminus as an ancillary marker for epithelioid hemangioendothelioma variant with YAP1-TFE3 fusion and other YAP1-related vascular neoplasms.

Epithelioid hemangioendothelioma (EHE) with YAP1-TFE3 fusion is a recently characterized distinctive variant of EHE that accounts for a small subset (<5%) of cases. It is composed of nests of epithelioid cells with voluminous pale cytoplasm and often shows focally vasoformative architecture. TFE3 immunohistochemistry (IHC) can be used to support the diagnosis; however, studies have questioned its specificity. Yes-associated protein 1 (YAP1), part of the Hippo signaling pathway, is expressed in normal endothelial cells, but becomes disrupted in EHE variant with YAP1-TFE3, such that only a small N-terminal region of YAP1 is expressed in the fusion protein. A recent study also reported YAP1 rearrangements in a subset of retiform and composite hemangioendotheliomas (RHE and CHE). In this study, we evaluated the diagnostic utility of an antibody directed against the C-terminus of YAP1 (YAP1-CT) for EHE with YAP1-TFE3, RHE, and CHE. In total, 78 tumors were included in the study: EHE variant with YAP1-TFE3 (n = 13), conventional (CAMTA1-positive) EHE (n = 20), pseudomyogenic hemangioendothelioma (n = 10), epithelioid hemangioma (n = 19), epithelioid angiosarcoma (n = 10), RHE (n = 4), and CHE (n = 2). IHC was performed using a rabbit monoclonal anti-YAP1 C-terminus antibody. EHE variant showed complete loss of YAP1-CT expression in 10 of 13 (77%) cases. All cases of RHE and CHE, with previously confirmed YAP1 rearrangements, also showed loss of YAP1-CT expression. Loss of YAP1-CT was seen in one conventional EHE (1/20; 5%). All other epithelioid vascular tumors showed retained YAP1-CT expression. Loss of expression of YAP1-CT appears to be associated with good sensitivity and specificity for EHE variant with YAP1-TFE3 fusion and may provide additional support along with TFE3 and CAMTA1 IHC in challenging cases. This marker may also be useful in the diagnosis of RHE and CHE.

Primary pleural epithelioid hemangioendothelioma: case report and review of the literature.

Epithelioid hemangioendothelioma (EHE) is an extremely rare vascular sarcoma with an unpredictable clinical behavior. Pleural EHEs have been associated with poor response to treatment and reduced survival. To date, no standard treatment for EHE is available. Here we report the case of a 53-year-old man who underwent radical surgery for a symptomatic primary pleural EHE. Clinical presentation was characterized by chronic pain in the left hemithorax with transitory flare, anemia, weight loss and progressive worsening of clinical conditions. After surgery, he resumed active life and normal daily activities and, at 8 months, 18F-FDG PET and computed tomography scan showed no radiological evidence of recurrent disease. Clinical signs of this rare disease, histological features, imaging findings and functional imaging are discussed. We also report a summary of other cases with resected pleural EHE and we briefly review the role of chemotherapeutic, immunomodulatory and antiangiogenic drugs for advanced disease.

Portal hypertension as an uncommon presentation of hepatic epithelioid hemangioendothelioma: a case report.

Hepatic epithelioid hemangioendothelioma (HEHE) is a vascular tumor with a low incidence rate. We report a case of a 26-year-old man who was referred to our hospital with a misdiagnosis of liver cirrhosis. On physical examination, ascites was noted. Chest and abdominal computer tomography scans showed coalescent lesions involving the peripheral liver with heterogeneous contrast enhancement and portal vein dilation due to portal hypertension. Extrahepatic metastasis was not observed. The biopsy with immunohistochemical stains suggested HEHE (Factor VIII, CD31, and CD34). This report describes an uncommon case of HEHE with non-cirrhotic portal hypertension.

[Epithelioid hemangioendothelioma with TFE3 translocation in soft tissue:a clinicopathological study].

Objective: To investigate the clinicopathological and molecular features, diagnosis and differential diagnosis of TFE3-rearranged epithelioid hemangioendothelioma (EHE). Methods Two cases of TFE3-rearranged EHE arising from soft tissues, diagnosed by the Pathology Department of the First Affiliated Hospital of Nanjing Medical University from 2013 to 2020 were observed. EnVision method was used for immunophenotyping, fluorescence in situ hybridization (FISH) was used to test TFE3 gene rearrangements and WWTR1-CAMTA1 fusion gene,and next-generation sequencing (NGS) was used to delineate the fusion transcripts. Results: Details of these two cases were as follows: case 1, male, 51 years old, with tumor in the right temporal region; case 2, female, 42 years old, with tumor in the right neck. The tumors showed progressive painless enlargement. Grossly, the tumor of case 1 was multinodular with unclear boundary and grayish red cut surface, while the tumor of case 2, originating from a vein, appeared as a firm, tan mass within vessel wall. Microscopically, both tumors showed moderate cellularity and were consisted of plump, epithelioid, or histiocytoid cells with eosinophilic cytoplasm and mild-to-moderate nuclear pleomorphism. Most of the tumor cells were arranged in solid or alveolar growth patterns, while some tumor cells showed intraluminal papillary growth pattern in case 1 and anastomosing vascular channels and extramedullary hematopoiesis in case 2. Immunohistochemically, the tumor cells showed diffuse positivity for CD31, CD34, ERG, and TFE3. FISH revealed TFE3 break-apart signals in two cases, but WWTR1-CAMTA1 gene fusion was not detected. NGS identified YAP1 (exon1)-TFE3 (exon6) fusion gene in case 2. Clinical follow-up information was available in both cases for a follow-up period of 15 and 59 months respectively. Patient 1 had a relapse 22 months after surgery, and was currently alive with the tumor. Patient 2 remained disease-free. Conclusions: TFE3-rearranged EHE is a rare molecular subtype of EHE, with accompanying characteristic morphologic features. However the morphologic spectrum remains under-recognized, and more experience is needed. Immunohistochemical and molecular examinations are helpful for the diagnosis and differential diagnosis of the disease.

Hepatic hemangioendothelioma: CT, MR, and FDG-PET-CT in 67 patients-a bi-institutional comprehensive cancer center review.

OBJECTIVE: To evaluate the imaging features of hepatic epithelioid hemangioendothelioma (HEH) on multiphasic CT, MR, and FDG-PET-CT. METHODS: Bi-institutional review identified 67 adults (mean age, 47 years; 23 M/44 F) with pathologically proven HEH and pretreatment multiphasic CT (n = 67) and/or MR (n = 30) and/or FDG-PET-CT (n = 13). RESULTS: HEHs were multifocal in 88% (59/67). Mean size of the dominant mass was 4.1 cm (range, 1.4-19 cm). The tumors were located in the peripheral, subcapsular regions of the liver in 96% (64/67). Capsular retraction was present in 81% (54/67 cases) and tumors were coalescent in 61% (41/67). HEH demonstrated peripheral ring enhancement on arterial phase imaging in 33% (21/64) and target appearance on the portal venous phase in 69% (46/67). Persistent peripheral enhancement on the delayed phase was seen in 49% (31/63). On MR, multilayered target appearance was seen on the T2-weighted sequences in 67% (20/30) and on the diffusion-weighted sequences in 61% (11/18). Target appearance on hepatobiliary phase of MRI was seen in 57% (4/7). On pre-therapy FDG-PET-CT, increased FDG uptake above the background liver parenchyma was seen in 62% (8/13). CONCLUSION: HEHs typically manifest as multifocal, coalescent hepatic nodules in peripheral subcapsular location, with associated capsular retraction. Peripheral arterial ring enhancement and target appearance on portal venous phase are commonly seen on CT. Similarly, multilayered target appearance correlating with its histopathological composition is typically seen on multiple sequences of MR including T2-weighted, diffusion-weighted, and dynamic contrast-enhanced multiphasic MR. KEY POINTS: • Hepatic epithelioid hemangioendotheliomas manifest on CT and MR as multifocal, coalescent hepatic nodules in peripheral subcapsular location, with associated capsular retraction. • Enhancement pattern on contrast-enhanced CT and MR can vary but peripheral ring enhancement on arterial phase and target appearance on portal venous phase are commonly seen. • Retrospective two-center study showed that cross-sectional imaging may help in the diagnosis.

Epithelioid hemangioendothelioma of the lung: CT findings and clinical course of 35 cases.

OBJECTIVES: To evaluate computed tomography findings and assess the clinical course of patients with pulmonary epithelioid hemangioendothelioma. METHODS: Patients diagnosed with pulmonary epithelioid hemangioendothelioma at our institution between 2000 and 2019 were retrospectively analyzed. Patients with pleural involvement were excluded. Computed tomography findings of the lung at diagnosis were classified into three patterns: multiple small nodules pattern (˂15 mm), multiple nodules with large lesions pattern (≥15 mm) and single lesion pattern. Additionally, the clinical course of patients was evaluated. RESULTS: Thirty-five patients (15 men and 20 women; median age, 44 years) with pulmonary epithelioid hemangioendothelioma were identified. The multiple small nodules pattern, multiple nodules with large lesions pattern and single lesion pattern were observed in 25 (71.4%), 8 (22.9%) and 2 (5.7%) patients, respectively. In 22 (62.9%) patients, extra-pulmonary epithelioid hemangioendothelioma lesions were found. Most patients were followed without initial treatment, while two patients with single lesion pattern underwent surgical resection. The median follow-up period was 63 months. Five-year overall survival rate of all patients was 96.3%. Latest clinical information revealed that 20 (20/25, 80%) patients with multiple small nodules pattern were alive without symptoms. In patients with multiple nodules with large lesion pattern, four (4/8, 50%) patients were alive without symptoms, three (3/8, 37.5%) patients were alive with symptoms and one (1/8, 12.5%) died. No recurrence was observed in patients with single lesion pattern. CONCLUSIONS: Multiple small nodules pattern was the most common findings of pulmonary epithelioid hemangioendothelioma. Patients with pulmonary epithelioid hemangioendothelioma have good prognosis.

Aberrant keratin expression is common in primary hepatic malignant vascular tumors: A potential diagnostic pitfall.

Malignant vascular neoplasms such as epithelioid hemangioendothelioma (EHE) and angiosarcoma (AS) can arise within the liver. The aim of this study was to study the expression of keratins CK7, AE1/AE3 and OSCAR in primary hepatic EHE and AS. 9 cases of hepatic EHE and 13 cases of hepatic AS were stained with ERG, CK7, keratin AE1/AE3 and keratin OSCAR. Their expression was graded as 1+ (1-25% of tumor cells positive), 2+ (26-50%), 3+ (51-75%) or 4+ (>75%). ERG was positive in all 9 (100%) EHEs and all 13 (100%) ASs. CK7 was positive in 5/9 (56%) EHEs (2, 1+; 1, 2+; 1, 3+; 1, 4+) and 1/13 (8%) AS (2+). Keratin OSCAR was positive in 6/9 (67%) EHEs (5, 1+; 1, 2+) and 4/13 (31%) ASs (2, 1+; 1, 2+; 1, 4+). Keratin AE1/AE3 was positive in 6/9 (67%) EHEs (3, 1+; 3; 2+) and 4/13 (31%) ASs (2, 1+; 1, 2+; 1, 4+). Overall, 6/ 9 (67%) EHEs were positive for at least one keratin marker, of which 5 were positive for all 3 keratins (AE1/AE3, OSCAR and CK7) while 1 was positive only for 2 keratins (OSCAR and AE1/AE3). 4/13 (31%) of ASs were positive for both keratins OSCAR and AE1/AE3, of which 1 case was also positive for CK7. Aberrant keratin expression is common in primary hepatic EHEs (67%) and ASs (31%). Awareness of this diagnostic pitfall is important for avoiding misdiagnosis of these primary hepatic malignant vascular tumors as carcinomas.

Maxillary epithelioid hemangioendothelioma: an especially rare malignant tumor mimicking periodontal disease.

BACKGROUND: Epithelioid hemangioendothelioma (EHE) is an especially rare, low-grade malignant vascular tumor that, according to WHO classification, is described as locally aggressive tumor with possible metastasis and makes up 1% of all vascular tumors. EHE is characterized by the accumulation of round, eosinophil-infiltrated endothelium cells; with vacuolation of their cytoplasm; frequent angiocentric inflammation; and myxohyaline stroma. This tumor is usually found in the liver, lungs, and bones and is especially rare in the mouth. CASE PRESENTATION: We present an 18-year-old Caucasian female whose oral cavity lesion had been misdiagnosed as marginal periodontitis. The patient was treated improperly for 2 years until she was referred to a maxillofacial surgeon. The patient complained only about gingival recession in the palatal area of her upper-right-side 13th, 14th, and 15th teeth. The lesion's clinical appearance was of locally ulcerated painless lesion that affect the underlying bone as seen in X-rays in the palatal side of the right canine and the first and second premolars. Patient underwent surgery for her present defect and reconstruction using allogenic bone transplant. The diagnosis of EHE was based on the bony destruction as seen in x-rays and in the accumulation of tumor cells that were 100% positive to CD31; CD34 and ERG to endothelial markers. During the 31-month follow-up period, the patient exhibited no clinical and radiographic complications. CONCLUSIONS: With this clinical case, we demonstrate that this rare tumor must be included in differential diagnoses of periodontal pathologies to perform histomorphological examination in a timely manner, which could lead to correct diagnosis and adequate treatment.

Pseudomyogenic hemangioendothelioma of bone treated with denosumab: a case report.

BACKGROUND: Pseudomyogenic hemangioendothelioma (PMHE) is a rare endothelial neoplasm that involves the bones in only 14% of all cases. The optimal treatment strategy has not been established. We herein report a case of primary PMHE in which denosumab treatment showed activity in both imaging studies and the clinical outcome. CASE PRESENTATION: A 20-year-old woman presented with worsening pain in her left ankle. Imaging studies showed multifocal fluorodeoxyglucose (FDG)-avid [maximum standardized uptake value (SUVmax), 15.95] osteolytic lesions in the bones of her left lower extremity. While waiting for the definitive pathologic diagnosis of PMHE, denosumab, a human immunoglobulin G2 monoclonal antibody against RANKL, was initiated to treat progressive bone absorption after curettage of one of the lesions. Denosumab induced osteosclerosis around the lesions and pain relief and was discontinued 4 years after its initiation. Although all of the multifocal lesions remained, they all became less FDG-avid (SUVmax, 2.6), and the patient developed no signs of new lesions or distant metastasis. CONCLUSION: Denosumab plays a certain role in prevention of bone destruction by PMHE through suppression of osteoclast-like giant cells and would be an excellent treatment for bone absorption by PMHE of bone.

Three cases of histologically proven hepatic epithelioid hemangioendothelioma evaluated using a second-generation microbubble contrast medium in ultrasonography: case reports.

BACKGROUND: Hepatic epithelioid hemangioendothelioma (HEH) is rare; it is reported in < 1 person in 1,000,000 individuals. For accurate diagnosis, information regarding multiple graphic modalities in HEH is required. However, there is very little information concerning Sonazoid® contrast enhanced ultrasonography (CEUS) in HEH. CASE PRESENTATION: The present report describes the histologically proven three HEH cases evaluated using Sonazoid® CEUS. Case 1 was a 33-year-old female patient with no relevant past medical history, who experienced right upper quadrant pain. Conventional abdominal US revealed multiple low echoic liver nodules with vague borderlines. In CEUS, the vascularity of the nodules was similar to that seen in the neighboring normal liver. Later in the portal venous and late phases (PVLP) and post vascular phase, washout of Sonazoid® was detected in the nodules. Case 2 was a 93-year-old female patient with a previous medical history including operations for breast cancer and ovary cancer in her 50's. Conventional abdominal US revealed multiple low echoic nodules, some of which contained cystic lesions. In the early vascular phase of CEUS, nodules excluding the central anechoic regions were enhanced from peripheral sites. Although the enhancement inside the nodules persisted in both the PVLP and post vascular phase, anechoic areas in the center of some nodules were not enhanced at all. Case 3 was a 39-year-old male patient presented with right upper-quadrant pain, without any relevant past medical history. Conventional abdominal US revealed multiple low echoic liver nodules. In the early vascular phase of CEUS, nodules were gradually enhanced from the peripheral sites as ringed enhancement. Sonazoid®was washed out from the nodules in the PVLP and post vascular phase. CONCLUSIONS: The most important feature was peripheral enhancement in the early vascular phase. In case 2, the enhancement of the parenchyma of liver nodules persisted even in the PVLP; indicating the lower degree of malignant potential than others. Actually, the tumors did not extend without any treatment in case 2. Since case 2 is the first case report of HEH with cystic lesions, in patients with liver nodules including cystic lesions, HEH is a potential diagnosis.