Fibrin-associate diffuse large B-Cell lymphoma arising in a left atrial myxoma: A case report and literature review✰,✰✰.

We report a 60-year-old male with fibrin-associated diffuse large B-cell lymphoma (fa-DLBCL) in left atrial myxoma. Echocardiography showed a mass (63 mm × 33 mm) in the left atrium. Histological inspection indicated fa-DLBCL on the surface of atrial myxoma incidentally, together with extensive fibrinous like exudation on myxoma surface. Malignant cells were localized in solid sheets and nests at the peripheral area of the fibrinous exudation which were positive for B-lineage markers (CD20+, CD79a+, PAX-5+) and in situ hybridization of EBV-encoded RNA (EBER). PCR amplification showed clonal rearrangement of immunoglobulin heavy chain (IgH) genes. The patient was still alive with no recurrence in the 35-month follow-up after surgery. We also did a detailed clinicopathological analysis and literature review, which indicated that fa-DLBCL was a heterogeneous entity.

Detection of GNAS mutations in intramuscular / cellular myxomas as diagnostic tool in the classification of myxoid soft tissue tumors.

BACKGROUND: Intramuscular / cellular myxomas and low-grade myxofibrosarcomas are two different tumor entities with a significant histological overlap, especially if dealing with small biopsies. Despite the morphological similarities, they differ considerably in their biological behaviour. Intramuscular / cellular myxoma rarely shows signs of recurrence and never metastasizes, in contrast to myxofibrosarcoma that tends to recur more aggressively and to metastasize haematologically. Therefore, it is of great importance to distinguish these lesions - evaluation of GNAS mutation status could be of tremendous help. METHODS: We reviewed 13 cases with intramuscular / cellular myxomas. The 13 cases included 5 men and 8 women, aged from 33 to 71 years (mean age 55.5 years). Immunohistochemistry was performed as well as next generation sequencing. Ten cases were located in the lower extremities and three cases were located in the upper extremities. Two lesions were initially misdiagnosed as a low-grade myxofibrosarcoma. RESULTS: Performing next generation sequencing 12 out of 13 specimens showed a GNAS mutation. CONCLUSIONS: Our findings demonstrate that GNAS mutations are more common in intramuscular / cellular myxomas, than had been reported in literature in the past. Next generation sequencing for determining GNAS mutation status on small biopsies or diagnostically challenging cases facilitates the diagnosis of intramuscular / cellular myxoma and separates this tumor entity from its mimics.

An optimized procedure for on-tissue localized protein digestion and quantification using hydrogel discs and isobaric mass tags: analysis of cardiac myxoma.

An optimized workflow for multiplexed and spatially localized on-tissue quantitative protein analysis is here presented. The method is based on the use of an enzyme delivery platform, a polymeric hydrogel disc, allowing for a localized digestion directly onto the tissue surface coupled with an isobaric mass tag strategy for peptide labeling and relative quantification. The digestion occurs within such hydrogels, followed by peptide solvent extraction and identification by liquid chromatography coupled to high-resolution tandem mass spectrometry (LC-MS/MS). Since this is a histology-directed on-tissue analysis, multiple hydrogels were placed onto morphologically and spatially different regions of interest (ROIs) within the tissue surface, e.g., cardiac myxoma tumor vascularized region and the adjacent hypocellular area. After a microwave digestion step (2 min), enzymatically cleaved peptides were labeled using TMT reagents with isobaric mass tags, enabling analysis of multiple samples per experiment. Thus, N = 8 hydrogel-digested samples from cardiac myxoma serial tissue sections (N = 4 from the vascularized ROIs and N = 4 from the adjacent hypocellular areas) were processed and then combined before a single LC-MS/MS analysis. Regulated proteins from both cardiac myxoma regions were assayed in a single experiment. Graphical abstract The workflow for histology-guided on-tissue localized protein digestion followed by isobaric mass tagging and LC-MS/MS analysis for proteins quantification is here summarized.

Expression of the Insulin-like Growth Factor-1 Receptor in Odontogenic Myxoma.

UNLABELLED: Odontogenic myxoma (OM) is a rare mesenchymal tumour arising in the jaws. The origin and pathogenesis of OM is poorly understood. The aim of this study was to characterize OM by immunolocalization of certain antigens in the tumour that are relevant for cellular differentiation, migration and maintenance. MATERIALS AND METHODS: Five OMs were immunohistochemically investigated for expression of nestin, CD133, podoplanin, and insulin-like growth factor 1 receptor (IGF-1R). RESULTS: OM failed to react with antibodies applied in this study, with the exception of IGF-1R in tumour cells. DISCUSSION: OM is a poorly characterized benign, invasive tumour of the jaws. The absence of stem cell marker in OM does not exclude possible temporary expression of these antigens during certain phases of tumour development. The identification of IGF-1R in OM is shared with numerous tumours and indicates the ability of these tumour cells to respond to growth factors.

Coronary Embolization from a Left Atrial Myxoma Containing Malignant Lymphoma Cells.

Systemic embolization from a primary cardiac tumor is a relatively frequent presentation. However, an acute myocardial infarction due to coronary embolization is rarely seen. We offer an unusual case of a 50-year-old man who presented with severe angina and was diagnosed with an inferolateral ST-segment-elevation myocardial infarction. Aside from otherwise healthy coronary arteries, his coronary angiogram revealed an acute occlusion of the first obtuse marginal branch, which was treated with balloon angioplasty. Because no residual plaque or dissection was found after the angioplasty, an embolic source was suspected. An echocardiogram then revealed a large mobile left atrial myxoma prolapsing into the left ventricle, so the patient underwent minimally invasive resection. Detailed pathologic examination of the myxoma revealed a concomitant high-grade B-cell lymphoma.

Prognostic prediction of troponins in cardiac myxoma: case study with literature review.

OBJECTIVE: It was supposed that troponins in cardiac myxoma patients might be in a same fashion as in the conditions without myocardial injury. In order to verify this hypothesis, troponins in cardiac myxoma patients were discussed by presenting a comprehensive retrieval of the literature with incorporating the information of a recent patient. METHODS: Postoperative detections of troponin I, creatine kinase isoenzyme MB (CK-MB) and N-terminal pro-B-type natriuretic peptide revealed elevated troponin I and CK-MB and normal N-terminal pro-B-type natriuretic peptide. Postoperative troponin I and CK-MB shared a same trend, reaching a peak value at postoperative hour 2, gradually decreased on postoperative day 1, and reached a plateau on postoperative days 7 and 13. A significant correlation could be noted between the postoperative values of the two indicators (Y = 0.0714X + 0.6425, r2 = 0.9111, r=0.9545, P=0.0116). No significant linear correlation between troponin I and N-terminal pro-B-type natriuretic peptide were found. Literature review of troponins in cardiac myxoma patients revealed the uncomplicated patients had a normal or only slightly elevated troponin before open heart surgery. However, the complicated patients (with cerebral or cardiac events) showed a normal preoperative troponin in 3 (23.1%) and an elevated troponin in 10 (76.9%) patients (χ2 = 7.54, P = 0.0169, Fisher's exact test). The overall quantitative result of troponin I was 2.45 ± 2.53 µg/L, and that of troponin T was 3.10 ± 4.29 mg/L, respectively. CONCLUSION: Troponins are not necessarily elevated in patients with a cardiac myxoma without coronary syndrome. By contrast, patients with a cardiac myxoma with an elevated troponin may herald the presence of an associated coronary event. An old cerebral infarct does not necessarily cause an elevation of troponin or B-type natriuretic peptide, or new neurological events, but might lead to a delayed awakening.

Renal myxoma: an unexpected differential diagnosis.

Myxomas are rare mesenchymal tumors that can appear in many anatomical locations, although they are mainly seen in heart and skin. To date, only twelve cases of pure renal myxomas have been reported in the literature. We describe a case of a young Cuban woman with an asymptomatic irregular cyst lesion in her left kidney which was eventually diagnosed as renal myxoma. We also provide radiological and pathological studies.

Significance of 18 F-FDG PET and immunohistochemical GLUT-1 expression for cardiac myxoma.

Cardiac tumours are relatively rare and are difficult to diagnose merely with imaging techniques. We demonstrated an unusual case of left atrial myxoma, displaying the successful detection by positron emission tomography using 2-deoxy-2-[18 F] fluoro-D-glucose (18 F-FDG PET), correlated closely to more intense and enhanced immunoreactivity with glucose transporter-1 (GLUT-1) in a substantial number of cardiac myxoma cells. Further prospective studies are needed to validate the significance of 18 F-FDG PET findings for cardiac myxoma and the association with immunohistochemical GLUT-1 expression in its tumour cells, after collecting and investigating a larger number of surgical cases examined with both of them. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/2991481941253449.

Plexiform angiomyxoid myofibroblastic tumor (PAMT) of the stomach. A case report focusing on its characteristic growth pattern.

Plexiform angiomyxoid myofibroblastic tumor (PAMT) is a rare mesenchymal tumor of the stomach. We report herein a case with CT findings, which illustrate the characteristic growth pattern of PAMT. A 27-year-old female patient visited our hospital because of epigastric pain and anemia. The CT scan showed a heterogeneous tumor in the gastric antrum, which was drastically enhanced with contrast medium, and consisted of a number of highly stained small nodules around the tumor rim. The resected tumor, 4.6 cm in size, was c-kit negative and SMA-positive by immunohistochemistry, and composed of bland spindle cells which were separated by abundant myxomatous stroma. The tumor showed plexiform growth in the entire stomach wall, with multiple nodules protruding outward within the serosa. The CT findings in this case reflect the characteristic PAMT growth pattern, and are distinct enough to differentiate it from gastrointestinal stromal tumor (GIST).

Selected case from the Arkadi M. Rywlin International Pathology Slide Club: aggressive angiomyxoma, left labial region in a postmenopausal woman.

Club members unanimously agreed with the diagnosis of an unencapsulated 8×2.5×3.6 cm aggressive angiomyxoma, which was invading the voluntary muscles of the pelvic floor beneath the left labium of a female aged 65. The tumor consisted of histologically bland, round, stellate to fusiform cells set in a myxocollagenous matrix with occasional mast cells, a few extravasated red cells, and prominent blood vessels varying from thin-walled capillaries 7 µm in diameter to larger thick-walled vessels >250 µm in diameter. The tumor cells stained positively for estrogen and progesterone receptors, vimentin, and desmin. A stain for the nuclear transcription factor HMGA2, which is emerging as a useful and relatively specific marker for aggressive angiomyxoma, was not performed. The tumor had not recurred 4 years after the surgical excision. One member commented that virtually all lesions diagnosed as aggressive angiomyxomas in superficial locations turn out to be either fibroepithelial stromal polyps or superficial angiomyxomas. None of the club had seen a metastasizing aggressive angiomyxoma nor had they any experience with gonadotropin hormone-releasing and luteinizing hormone-releasing agonists therapy, which have been reported to cause tumor regression.

[Case report. Aggressive angiomyxoma of vagina. A rare tumor diagnosed]. / Angiomixoma agresivo de vagina: un tumor poco diagnosticado.

The case of a female patient of 35 years of age, with a pedunculated tumor dependent of the vagina, of approximately 25 x 12 x 8 cm, who had a wide resection. The report was consistent with myxoid aggressive angiomyxoma. This is a myxoid mesenchymal neoplasm of slow growth, which mainly appears in deep soft tissues of the pelvic, genital or perineal areas of adult women. It is usually diagnosed after surgical resection by histopathologic examination. Routine evaluation includes: complete physical examination, imaging and pathology report of diagnostic confirmation.

Cardiac myxoma with glandular differentiation: an immunohistochemical and ultrastructural study.

A case of cardiac myxoma with glandular differentiation is reported. The patient did not have elements of the Carney triad or syndrome. The tumor was mainly composed of characteristic stellate cells in a focally collagenized, myxoid stroma, along with aggregates of glandular-forming epithelial cells, with mucin-containing intra- and intercellular lumina. Ultrastructurally, these gland spaces displayed short, straight microvilli and junctional complexes. The epithelial cells were positive for cytokeratin 7 and negative for cytokeratin 20. Calretinin was positive in the stellate cells and negative in the epithelial component. The potential origin from pluripotent mesenchymal cells or from seeded stem cells is hypothesized for glandular differentiation in myxomas. Further studies are required to unravel the relationship between stellate cells and the diverse heterologous components reported in these tumors.

[Angiomyxoma: always myxoid, sometimes aggressive]. / Anjiomiksom: Her Zaman Miksoid, Bazen Agresif.

Angiomyxoma is a distinct soft tissue tumor characterized by the presence of prominent myxoid matrix and numerous thin-walled blood vessels. This tumor has a predilection for the trunk, head and neck, extremities, and genitalia. It is a benign tumor and total excision is curative. Recurrence is rare except for aggressive angiomyxomas. A 12-year-old girl with a 10-year history of a subcutaneous mass on the left gluteus measuring 4.5x4x3 cm had been referred. The tumor was encapsulated and was located in the reticular dermis and subcutaneous tissue, composed of stellate cells with mucinous stroma. Thin-walled blood vessels were prominent. Immunohistochemically, tumor cells were immunoreactive for vimentin. No immunoreactivity was present for estrogen receptor, CD34, smooth muscle actin, S-100 protein and desmin. The purpose of this report is to present a classical example of an isolated superficial angiomyxoma and discuss the differential diagnosis, because of its relatively infrequent occurence.

Detection of herplex simplex virus-1 and -2 in cardiac myxomas.

The etiology of sporadic cardiac myxomas remains elusive. The tendency for these lesions to recur following resection, their immunopathological characteristics, along with their histological and molecular profile, may implicate the presence of an infective agent in this type of tumor. In this study, we investigated the presence of herpes simplex virus (HSV) DNA in a cohort of cardiac myxomas in a tertiary referral centre. Twenty-nine formalin-fixed paraffin-embedded (FFPE) sporadic cardiac myxomas were obtained, 17 of which were shown to be informative. These were compared to 19 macroscopically and microscopically normal heart tissue specimens. The detection of HSV-1 and -2 genomic sequences was achieved with the use of a combined nested PCR-Restriction Fragment Length Polymorphism methodology. The presence of HSV-1 and/or -2 DNA was demonstrated in 6 of 17 (35%) informative sporadic cardiac myxomas, whereas no HSV DNA was detected in normal heart tissues (P < 0.01). The existence of HSV-1/2 DNA in sporadic cardiac myxomas, along with its absence from normal heart tissues, reinforces the possibility that HSV infection might be involved in the development of these lesions. Our findings raise the point of anti-HSV medication postsurgically with a potential benefit in reducing the rate of recurrences.

Aggressive angiomyxoma of the vaginal wall at the initial stage: a case report.

Aggressive angiomyxoma (AA) is a rare mesenchimal tumor usually located in the pelvic and perineal region. Less than 30 cases of aggressive angiomyxoma with vaginal location have been reported in the literature up to this date. The authors report the case of a 50-year-old female patient diagnosed with vaginal AA whose characteristics at its initial stage were macroscopically indistinguishable from those of a polypoid lesion. Therefore this case suggests that this type of tumor should be considered as part of the differential diagnosis of vaginal polypoid lesions.

[Superficial angiomyxoma of the parotid region and review of the literature]. / Angiomixoma superficial de la región parotídea y revisión de la literatura.

Superficial angiomyxoma (SA) is a rare benign cutaneous neoplasm first described by Allen et al in 1988. To the best of our knowledge, we report the first case of superficial angiomyxoma located in the parotid region. We also stress the importance of distinguishing this entity from other lesions that may be involved in this location such as cutaneous neoplasms, parotid tumours or cysts. We emphasise the need to rule out the Carney complex, which has been associated with these tumours.

Survivin expression in cardiac myxoma.

BACKGROUND: Cardiac myxoma, the most common primary tumor of the heart, has variable clinical presentations and an immunohistochemical profile. Survivin, an antiapoptosis protein, may play an important role in the causes of cardiac myxoma. This investigation will report the expression pattern of survivin in cardiac myxomas. METHODS: This study included 40 patients with cardiac myxoma, who were treated with surgical excision of the lesion. Detailed clinical parameters were reported and the expression of survivin was studied by immunohistochemical staining. RESULTS: The patient population was comprised of 24 (60%) women and 16 (40%) men. The mean age of the patients was 42 years, with an age range of 30 to 63 years. All study cases were sporadic myxomas rather than familial myxoma. Patients were asymptomatic (20%), or had dyspnea (40%), stroke (15%), chest pain (12%), and fever (12%) on presentation. All lesions were located in the left atrium. The location of the myxoma and clinical events did not differ in terms of pathological changes, such as vascular proliferation, inflammation, cellularity, hyaline, calcification and thrombosis. Cardiac myxoma was characterized by a survivin dependent pathway with 100% immunohistochemical staining in the cytoplasm and the distribution in scoring system of survivin expression were 1 case (2.5%) in score 1; 12 cases (30%) in score 2; 12 cases (30%) in score 3 and 15 (37.5%) in score 4. CONCLUSION: Cardiac myxomas demonstrate strong expression of survivin in the cytoplasm. This implies survivin may play an important role in the apoptosis pathway in cardiac myxomas.

Clinical and pathologic profile of angiomyxomas of the orbit.

PURPOSE: To describe clinical, imaging, and histopathologic features of angiomyxomas of the orbit, which are extremely rare tumors in the orbit. METHODS: A retrospective review of clinical case records and imaging findings of histopathologically diagnosed cases of angiomyxoma over a period of 8 years (2001-2008). The histopathologic features were studied by routine hematoxylin-eosin staining, special stain (Alcian blue), and immunohistochemistry. RESULTS: Four cases (2 male and 2 female) with a mean age of 35 years (range, 28-40 years) were diagnosed as angiomyxoma. Two of these were angiomyxomas, and 2 were aggressive angiomyxomas. All patients presented with gradual progressive proptosis. The mean duration of symptoms was 10.5 months (range, 5-24 months). There was associated reduction in the visual acuity in 2 cases. The superior orbit was involved in all 4 patients. CT scan showed a heterogeneously enhancing irregular mass confined to the superior orbit. Surgical removal of the mass was performed in all 4 cases. On follow-up, there was recurrence at 6 months in 1 case, which was histopathologically diagnosed as an angiomyxoma. CONCLUSIONS: Angiomyxoma is an extremely rare, locally aggressive orbital tumor, occurring in the third to fourth decade of life. Complete excision is the treatment of choice. These tumors are likely to have a recurrence due to their infiltrative growth and require long-term follow-up.