Endovascular papillary angioendothelioma-like tumour associated with lymphoedema

A case of endovascular papillary angioendothelioma-like tumour associated with lymphoedema is described. Microscopically, the tumour was composed of anastomosing vascular channels, some of which contained papillary projections, producing tuft-like or glomeruloid appearances. The dermis also showed moderate lymphoedema and lymphocyic infiltrate. The tumour resembled endovascular papillary angioendothelioma but also had several features that differed from typical examples: occurrence in an old patient and less prominent endothelial hobnail features and lymphocytic infiltrate. Three types of proliferating cells were observed: 1 mature flattened endothelial cells, which were strongly positive for endothelial markers (factor VIII-related antigen, CD31, CD34) and bound ulex europaeus agglutinin 1; 2 immature endothelial cells with round nuclei and vacuolated or pale cytoplasm, which were strongly positive for CD31 and muscle-specific actin (HHF35) and focally positive for other endothelial markers; and 3 stromal spindle cells in papillary or glomeruloid areas, which were positive for vimentin, HHF35, and alpha-smooth muscle actin but negative for desmin. The tumour was diploid by flow cytometry. The patient was well without disease twelve months after the excision. We postulate that this tumour was caused by circulatory disturbance, namely lymphoedema associated with syringomyelia and a Charcot's joint.     

Immunohistochemical investigation of selected endothelial markers in pulmonary epithelioid haemangioendothelioma

Epithelioid haemangioendothelioma (EH) is a very rare neoplasm. It is assumed that these tumours derive from vascular endothelial cells. The aim of the study was to identify the immunohistochemical profile of tumour cells in lung EH. The unique material consisting of eight cases of lung EH was collected and examined by immunohistochemistry with three antibodies: CD-31, CD105, both marking vascular endothelial cells, and D2-40, marking lymphatic endothelial cells. In all cases, the cytoplasm of tumour cells showed widespread expression of CD-31. Reaction with CD-105 antibody gave a positive result mainly in the cytoplasm of tumour cells located at the periphery of tumours, especially in highly cellular neoplasms containing spindle cells. Reaction with D2-40 antibody in most cases was negative. The presence of a few capillary vessels with positive endothelial cells was revealed in two cases at the periphery of the tumour. Only in one case of a highly cellular tumour did a small portion of spindle cells show a positive reaction to D2-40. The above studies confirmed the origin of EH mainly from vascular endothelial cells. Medications inhibiting vascular endothelial growth factors can be considered as a treatment option for multifocal EH that does not qualify for surgical intervention.     

Low grade fibromyxoid sarcoma: clinicopathological analysis of eleven new cases in support of a distinct entity

Low grade fibromyxoid sarcoma is a recently recognized, uncommon soft tissue neoplasm with a tendency to develop in deep soft tissue of young adults. Diagnostic criteria have not been well defined and this tumour has not been widely accepted as a distinct entity. Eleven new cases are reported here for which reproducible histological features are described and in which the immunohistochemical profile of the tumour cells is documented for the first time. Ten of the eleven patients were male and the majority were young or middle-aged adults (median age 45 years). All except one of the tumours were situated in deep soft tissue. Lower limb (four cases) and chest wall (three cases) were the commonest primary sites; one case each arose in the groin, buttock, axilla and retroperitoneum. Follow-up (median duration 6 years) was available in nine patients. Six developed local recurrence and in five cases recurrences were multiple. Pulmonary metastasis occurred in one patient. All tumours were characterized by the presence of bland spindle cells, showing a mainly whorled or focally linear arrangement, set in alternating areas with a fibrous or myxoid stroma. Tumour cells were small, spindle to stellate, with poorly defined, palely eosinophilic cytoplasm and hyperchromatic ovoid nuclei. Most tumour cells showed strong staining with antibodies to vimentin, while occasional cells stained positively for actin, desmin and cytokeratin, in keeping with focal myofibroblastic differentiation. Ultrastructural examination in one case revealed features of fibroblasts. Careful consideration of the morphological and immunohistochemical features of these tumours permits a positive diagnosis of low grade fibromyxoid sarcoma and allows its distinction from a number of other benign and malignant soft tissue neoplasms.     

Expression of D2-40 in lymphatic endothelium of normal tissues and in vascular tumours

AIMS: To evaluate the expression of D2-40 in normal lymphatic endothelium and vascular tumours or tumour-like lesions of the skin and soft tissue. D2-40 is a novel monoclonal antibody to a Mr 40 000 O-linked sialoglycoprotein that reacts with a fixation-resistant epitope in lymphatic endothelium. METHODS AND RESULTS: Formalin-fixed paraffin-embedded sections from 30 normal tissue samples, including skin, soft tissue, stomach, and colon, and 84 vascular tumours or vascular tumour-like lesions were immunostained with monoclonal antibodies to D2-40 and CD31. Normal lymphatic endothelial cells in all normal tissues expressed D2-40. Its positive staining delineated flattened channels or open spaces lined by a single layer of endothelial cells whose lumena were sometimes filled with lymphocytes. Ten of 10 cases of lymphangioma, nine of 10 Kaposi's sarcomas (KSs), one of five spindle cell haemangiomas, one of one reactive angioenodotheliomatosis, one of one vascular transformation of lymph node sinuses, three of three Dabska tumours, one of 10 epithelioid haemangioendotheliomas (HEs) and seven of 15 angiosarcomas were positive for D2-40. Positively staining angiosarcomas were characterized by epithelioid or papillary endothelial cells. Twenty-two non-spindle cell haemangiomas, one retiform HE and one Kaposiform HE, and five glomus tumours were negative for D2-40. In comparison, CD31 was expressed in five of 10 lymphangiomas, nine of 10 KSs, 27 of 27 haemangiomas, three of three Dabska tumours, 10 of 10 epithelioid HEs, 15 of 15 angiosarcomas and one of one each of retiform HE, Kaposiform HE, reactive angioendotheliomatosis, and vascular transformation of node sinuses. Five glomus tumours were negative for CD31. CONCLUSIONS: The monoclonal antibody D2-40 is a highly sensitive and specific marker of lymphatic endothelium in normal tissue and a subset of vascular lesions, including KS, Dabska tumour, and lymphangioma. The findings support the concept that these tumours show at least partial lymphatic endothelial differentiation. Subsets of angiosarcomas and HEs show both vascular and lymphatic endothelial differentiation. D2-40 can be used in a panel of markers to classify vascular tumours. There is no requirement for epitope retrieval. This novel monoclonal antibody also has the potential for increasing the accuracy of detection of lymphatic invasion in primary tumours and could be widely applied for this purpose in surgical pathology.     

High-grade extraskeletal myxoid chondrosarcoma: a high-grade epithelioid malignancy

AIMS: Extraskeletal myxoid chondrosarcoma is typically a low-to-intermediate grade sarcoma that is associated with a prolonged clinical course. High-grade forms are rare and not well characterized. In this series we report the clinicopathological, immunohistochemical and ultrastructural findings in four cases of high-grade extraskeletal myxoid chondrosarcoma. METHODS AND RESULTS: The patients were three men and one woman (ages 34-73 years) with tumours located in the thigh (two cases), paraspinal soft tissue and perineum. Three patients had metastases, one at 12 weeks, one at 10 months, and one at presentation of recurrent tumour. In the latter case the original tumour was low grade and became high grade when it recurred 3.5 years later. All three patients died of disease. One patient was lost to follow-up. The most striking histological feature in all four tumours was the presence of numerous large epithelioid cells. These cells were arranged in cords within myxoid matrix and in sheets devoid of matrix. Two tumours had areas of conventional extraskeletal myxoid chondrosarcoma intermixed with the high-grade areas. One tumour showed transition to high-grade spindle cell sarcoma. One tumour had cells with rhabdoid features. Immunohistochemically, two tumours focally expressed S100 protein, and one focally expressed EMA. All were negative with cytokeratin, desmin, smooth muscle actin, HMB45, CD31 and CD34. Ultrastructural features in three cases were compatible with chondrosarcoma; one tumour had aggregates of microtubules within rough endoplasmic reticulum, a characteristic feature of this tumour. CONCLUSIONS: High-grade extraskeletal myxoid chondrosaroma is a rare and aggressive soft tissue sarcoma, and should be included in the differential diagnosis of other epithelioid malignancies.     

Intraglomerular metastasis: a necropsy study.

Intraglomerular metastasis is a rare phenomenon. Four cases are reported here. The primary malignancies in these four cases were squamous cell carcinoma of the lung, adenocarcinoma of pancreas, haematological malignancy with a malignant intrapulmonary teratoma, and undifferentiated pleural mesothelioma. There was no significant renal functional impairment in any case except for mild proteinuria in one. Histopathology showed tumour cells in the mesangium, in the glomerular tufts replacing the endothelial cells, as well as in an extracapillary location replacing the parietal cells. In one case, tumour cells formed crescent-like structures. Such tumour deposits were better appreciated with special stains. The presence of intraglomerular metastasis indicates dissemination of the malignancy and hence a poor prognosis even though there is no significant impairment of renal function.     

Diffuse sclerosing papillary carcinoma of the thyroid gland: immunohistochemical analysis of the local host immune response

Surgical specimens from four patients with diffuse sclerosing papillary carcinoma of thyroid were examined by electronmicroscopy. In addition, immunohistochemical examination using a panel of monoclonal and polyclonal antibodies was carried out in order to investigate the expression of HLA-DR antigen, the presence of Langerhans' cells and the phenotypic characteristics of the inflammatory infiltrate. The ultrastructural study showed that the intraglandular dissemination, typical of this tumour, was due to massive lymphatic invasion. Many Langerhans' cells were observed among tumour cells and in the lymphoid infiltrates in proximity to tumour foci. HLA-DR expression was seen on macrophages, Langerhans' cells, endothelial cells, lymphoid cells, many tumour cells and in some non-neoplastic follicles close to tumour clusters and lymphoid infiltrates. The immunohistochemical analysis of the inflammatory infiltrates showed a high proportion of B- and T-cells, and moderate numbers of plasma cells. Our results suggest that the tumour-specific immune response can give rise to an autoimmune reaction involving non-neoplastic follicles. It is suggested that this could be one of the mechanisms responsible for immunofacilitation of tumour growth.     

Diverse differentiation in malignant peripheral nerve sheath tumours associated with neurofibromatosis-1: an immunohistochemical and ultrastructural study

AIMS: The diverse histological features in malignant peripheral nerve sheath tumours (MPNSTs) associated with NF-1 were investigated by immunohistochemical and electron microscopic analysis. Our study is focused on the differentiation of the tumour cells in the heterogeneous components. METHODS AND RESULTS: Twenty-three cases were classified as conventional type, epithelioid type, anaplastic type, and heterogeneous type, and divided into three groups by the presence of S100 protein (S100)-positive cells in each tumour; Group A was defined as having >50% S100+ cells, Group B as having <50%, and Group C as cases with no positive cells. To investigate the differentiation of the tumour cells, the morphology and immunoreactivity for neural or mesenchymal markers among the three groups were compared. For the identification of Schwannian, perineurial, and endoneurial differentiation, markers for S100, EMA and CD34 were used, respectively. In three tumours of the Group A type, there were no cases showing differentiation towards perineurial or endoneurial cells, or formation of heterogeneous components. In nine tumours of the Group B type, one tumour expressed EMA and CD34, suggesting probable perineurial and/or endoneurial differentiation. One tumour showed rhabdomyoblastic differentiation. Three tumours showed cartilaginous or osteogenic differentiation, and one of the three also showed a focal vascular differentiation. The surrounding areas of the heterogeneous components were composed of mixed S100+ cells and S100- cells. S100- cells in the areas were positive for CD34 in one case. In 11 tumours of Group C type, one tumour expressed EMA and CD34 suggesting perineurial and/or endoneurial cell differentiation. Three tumours showed rhabdomyoblastic differentiation. The tumour cells around the heterogeneous components in the three cases were negative for EMA and CD34. CONCLUSION: Our results suggest that tumour cells differentiating to Schwann cells are not the only component of MPNSTs. Furthermore, tumour cells other than Schwann cells are largely related to the formation of the heterogeneous components in MPNSTs associated with NF-1.     

Cutaneous perineurioma: a poorly recognized tumour often misdiagnosed as epithelioid histiocytoma

AIMS: Eleven cases of cutaneous perineurioma were studied to further characterize the histological features of this entity. METHODS AND RESULTS: The histological and immunocytochemical features of 11 cases of cutaneous perineurioma were studied and detailed by two pathologists. Clinical data were obtained from the referring clinician. Seven patients were female and four were male with ages ranging from 19 to 67 years (median 41 years). Six lesions arose on the leg. Macroscopically lesions ranged from 4 mm to 14 mm in maximum diameter (median 7 mm). Diagnostic histological features included a nonencapsulated but sharply demarcated tumour with a dumbbell architecture. The tumour cells were spindle-shaped with delicate inconspicuous cytoplasm and arranged in sheets, whorls or with a vague fascicular pattern. Epithelioid cells with moderate amounts of eosinophilic cytoplasm were frequently admixed with the spindle cells. One tumour had trabeculae of cells embedded within a dense collagenous stroma as described in sclerosing perineurioma. One case displayed a prominent myxoid stroma. Three further cases contained small foci of fibrosis or myxoid change suggesting a morphological spectrum exists in cutaneous perineurioma. Mitoses were exceptionally rare and necrosis and significant cytonuclear pleomorphism was not found. All tumours were epithelial membrane antigen (EMA) positive. Six cases showed focal positivity for factor XIIIa. Follow-up ranged from 5 months to 6 years (median 1 years). No tumour recurred or metastasized. CONCLUSIONS: The histological appearance of this tumour is broader than hitherto realized. Several cases in this series were misdiagnosed histologically and cutaneous perineuriomas may be more common than currently appreciated.     

Rejection nephropathy before and after therapeutic administration of cyclosporin A

During 1983 to 1986 41 patients were treated with Cyclosporin A (CyA) following kidney allotransplantation (TPL). 31 received the first (29 extra- and 2 intrafamilial) graft; in 10 there was second TPL, in 9 cases under high-risk conditions, where the first graft had been destroyed by (hyper)acute rejection or by rapidly progressive rejection with early vascular lesion. 21 needle biopsies and 5 excised grafts which had been collected 5 days to 18 months after TPL were examined by light microscopy and in addition 6 of the former also underwent electron and immunofluorescence microscopic study. The glomeruli showed discrete, inconstant segmental lesions but the ultrastructure also revealed severe general endothelial swelling. The tubular system had nonspecific degenerative changes of varying extent. In 11 patients focal cytoplasmic microvacuoles appeared in proximal tubular epithelia; there were also inconstant hyaline droplets, microcalcifications, and intratubular crystals. Electron microscopy revealed multiple round dense intramitochondrial inclusions in proximal tubules. The ultrastructure of the microvacuoles resembled that of "osmotic nephropathy". The rejection infiltrate and interstitial fibrosis of various degree did not essentially differ from those of conventionally treated grafts. In 7 patients cortical arterioles and small arteries exhibited a stenosing lesion (toxic?). In 3 cases metachromatic "mucoid" thickening of intima was prominent. Ultrastructure studies showed swollen endothelial cells with numerous globular dense bodies and a severe defect in the leiomyofibrils of muscle cells of the media. Hyperplasia of juxtaglomerular apparatus was apparent in 7 patients. Immunofluorescent microscopy of two biopsies from subsequently excised grafts visualized IgM, C3, and fibrinogen in small arteries and some glomerular capillary loops. Three early nephrectomies were caused by infarct-like necrosis. The discussion deals with differences between CyA- and conventionally treated grafts, diagnostic features, interpretation of findings, and measures following biopsy. In our patients with continual CyA-treatment no case of clinically and morphologically typical obliterative arterio-arteriolopathy (OA) and rapidly progressive irreversible rejection has as yet been noted.     

Superficial cervico-vaginal myofibroblastoma: a report of five cases

AIMS: To describe the pathological and immunohistochemical features of five cases of superficial cervico-vaginal myofibroblastoma (SCVM), a recently described mesenchymal tumour affecting middle-aged and elderly females. METHODS: The histological features of five cases of SCVM arising in four patients were reviewed including one case which recurred locally 9 years after initial excision biopsy. All cases were immunostained using the streptavidin-biotin technique using antisera to vimentin, smooth muscle actin, desmin, S100 protein, cytokeratin, h-caldesmon, calponin, CD99, CD117 (c-kit), bcl-2, oestrogen receptor and progesterone receptor. RESULTS: The patients were aged from 40 to 71 years (mean 55.2 years). The tumours were situated within the vagina (four cases) and cervix (one case) and ranged from 16 to 45 mm in greatest dimension. One patient had two separate vaginal SCVM. The tumours were characterised by uniform spindle and stellate-shaped cells separated by a collagenous or myxoid stroma. No mitotic activity was identified. Characteristically the tumours were well circumscribed and separated from the surface epithelium by a rim of normal stroma. The initial and recurrent tumours in one patient were similar except for increased stromal collagen in the recurrence. All tumours were immunoreactive for vimentin, desmin, CD34, CD99, bcl-2, calponin and hormone receptors while two tumours showed focal smooth muscle actin expression. There was no expression of S100 protein, h-caldesmon, CD117 or cytokeratin. CONCLUSIONS: SCVM appears to be a relatively distinct lesion although there is some histological and immunophenotypical overlap with other mesenchymal tumours, particularly fibroepithelial polyp, leiomyoma and solitary fibrous tumour. As local recurrence developed 9 years after intial treatment in one patient, long-term clinical follow-up would seem appropriate.     

The histogenesis of angiosarcoma of the face and scalp: an immunohistochemical and ultrastructural study

Thirteen cases of angiosarcoma of the face and scalp have been examined using immunohistochemistry and electron microscopy. Endothelial cell markers have been employed in an immunoperoxidase technique on tissue that has either been routinely processed, periodate-lysine paraformaldehyde fixed (PLP) and cold processed, or fixed in methacarn. A consistent pattern of endothelial cell labeling was only achieved in the PLP fixed tissue. In this fixative the angiosarcomas were factor VIII related antigen negative, Ulex europaeus lectin positive, laminin positive, unlabelled by the monoclonal antibody PAL-E, and positively labelled by the monoclonal antibody EN4. Ultrastructural examination of four cases showed evidence of vascular lumina in all tumours. Weibel-Palade bodies were seen in only one case but three tumours showed some evidence of tight junction formation and marginal folding. Thus, our cell marker studies can be interpreted as consistent with a lymphatic derivation for this type of angiosarcoma but in contra-distinction the ultrastructural studies showed tumour channels with features suggestive of blood vessel differentiation.     

Capsular intravascular endothelial hyperplasia: a peculiar form of vasoproliferative lesion associated with thyroid carcinoma

AIMS: Florid vasoproliferative processes are uncommon in the thyroid gland. We report three cases of an unusual vasoproliferation involving the capsular blood vessels of thyroid carcinoma. METHODS AND RESULTS: The histological diagnoses of the three cases were made on conventional histological sections. Two cases were minimally invasive follicular carcinomas and one case was an encapsulated variant of papillary carcinoma. Some blood vessels in the tumour fibrous capsule were filled with spindly cellular proliferations forming irregular vascular clefts and papillae. Immunohistochemical studies for CD31, CD34 and muscle-specific actin confirmed that the spindly cells were mostly endothelial cells variably supported by pericytes. CONCLUSION: This peculiar intravascular endothelial hyperplasia by itself should not be mistaken for vascular invasion by tumour, but evidence of malignancy must be diligently sought by extensive sampling because the lesion has thus far been consistently associated with malignant thyroid neoplasms.     

Immunohistochemical study of the inflammatory infiltrate associated with equine squamous cell carcinoma.

The distribution of T (CD3), B (CD79) lymphocytes, immunoglobulin (IgG, IgM and IgA)-producing plasma cells, macrophages (lysozyme, Mac387) and MHC Class II antigen was analysed in the inflammatory infiltrate associated with 19 equine squamous cell carcinomas (SCCs) and six cases of precancerous lesions (actinic keratosis). The SCCs came from the penis (11 cases), conjunctiva (four), skin (two), nasal cavity (one) and oral cavity (one). Seven cases were well-differentiated and 12 moderately differentiated. Nine cases showed no invasion of peritumoral deep tissues (locally invasive), whereas the remaining 10 cases were highly invasive. An abundant inflammatory infiltrate was associated with the majority of the SCCs and with lesions of actinic keratosis. This infiltrate was composed mainly of CD3(+)T lymphocytes, CD79(+)B cells and numerous IgG(+)plasma cells; IgM- and IgA-producing plasma cells were scarce and variable, respectively. Macrophages were usually numerous. Macrophages, lymphocytes, intra-epithelial dendritic cells and fibroblasts expressed MHC Class II antigen. No significant correlation was found between the nature of the inflammatory infiltrate and the SCC histological grade or degree of invasion, suggesting that the local anti-tumour immune response failed to prevent tumour invasion or metastasis. MHC Class II was expressed by a variable number of neoplastic epithelial cells in four SCCs, all of which were only locally invasive. In addition, in areas where SCC cells expressed Class II antigen, numerous CD3(+)T lymphocytes were present and some of them were associated with degenerate tumour cells. These findings suggest that the expression of MHC Class II by neoplastic cells induces an improved local anti-tumour immune response.     

Dedifferentiated leiomyosarcoma of the intestinal tract: histological,ultrastructural and immunohistochemical examinations

Summary Six cases of dedifferentiated leiomyosarcoma of the small and large bowel are presented with histological, ultrastructural and immunohistochemical examination. One case arose in the jejunum, two in the ileum, and the other three in the large intestine. The tumours were submucosal in four cases with large areas of ulceration; two were polypoid. Four tumours showed typical leiomyosarcomatous appearance with dedifferentiated components and two were typical leiomyosarcomas at the primary site with differentiated components only in metastatic foci. By immunohistochemistry, typical leiomyosarcomatous areas showed a positive reaction for muscle-specific actin (MSA), MB1, MB2 and myosin. In contrast, desmin-positive cells were scattered throughout the tumour or were not present. Tumour cells in dedifferentiated components were positive for alpha-1-antitrypsin and alpha-1-antichymotrypsin in all cases but one; neuron specific enolase, MB1, MB2 and myosin were positive with variety. MSA was faintly positive in only a few tumour cells of two cases and desmin was not detected in any of the cases studied. Ultrastructurally, tumour cells in typical leiomyosarcomatous areas demonstrated evident smooth muscle features, although in dedifferentiated areas they lacked such features except in one case. Our results indicate that dedifferentiated elements may derive from ordinary leiomyosarcoma and loose muscle features due to dedifferentiation.     

Cardiac myxoma: an immunoperoxidase study of histogenesis

Eleven surgically excised left atrial myxomas have been stained for factor VIII related antigen (VIII-RA) and actin by the peroxidase-antiperoxidase technique. Most tumour cells were negative for VIII-RA. However a population was identified forming cords and vascular channels which possessed a core or lining of tumour cells with an endothelial morphology which were positive. Tumour cells lining vessel-like invaginations of the surface also showed focal positive staining. The staining pattern for actin precisely mirrored that for VIII-RA. These findings support the established theory that cardiac myxomas arise from primitive endocardial or subendocardial mesenchymal cells with the potential to differentiate towards endothelial cells. They are incompatible with the theory that these tumours originate from cardiac endothelium.     

Histopathological and immunophenotypic features of testicular tumour of the adrenogenital syndrome

Wang Z, Yang S, Shi H, Du H, Xue L, Wang L, Dong Y & Han A
(2011) Histopathology 58, 1013–1018
Histopathological and immunophenotypic features of testicular tumour of the adrenogenital syndrome Aims: Testicular tumour of the adrenogenital syndrome (TTAGS) is a rare neoplasm histologically resembling Leydig cell tumour (LCT). We report six cases of TTAGS and analyse histopathological and immunophenotypical features that distinguish TTAGS from LCT. Methods and results: Six cases of congenital adrenal hyperplasia with bilateral TTAGS were examined histologically and immunohistochemically and compared to seven cases of testicular LCT. TTAGS was characterized histologically by sheets of polygonal cells separated by dense fibrous tissue with focal lymphocyte infiltration. All cases of TTAGS lacked cytological atypia except for one, which displayed scattered large pleomorphic, nuclei with one or two prominent nucleoli and sporadic mitotic figures. Immunohistochemically, all cases of TTAGS showed diffuse and strong positivity for CD56 and negative reactivity for androgen receptor. Reactivity for synaptophysin varied from focal (five cases) or diffuse (one case). In contrast, LCT displayed focal weak to moderate or negative reactivity for CD56 and focal weak or negative reactivity for synaptophysin, but positive reactivity for androgen receptor in six of seven cases. Conclusions: In addition to clinical information, biochemical profile and histopathological findings, our results suggest that immunohistochemistry using a panel of antibodies including CD56, synaptophysin and androgen receptor is helpful in differentiating TTAGS from LCT.     

伴菊形团形成的胶质神经元肿瘤5例临床病理分析

目的探讨伴菊形团形成的胶质神经元肿瘤(rosette-forming glioneuronal tumour,RGNT)的临床病理学特征。方法收集南京医科大学第一附属医院病理科2014年11月~2018年7月诊治的5例RGNT,行HE、免疫组化染色以及分子检测,并复习相关文献。结果5例均可见大小一致的神经细胞菊形团和(或)假菊形团结构,神经细胞核圆形,核仁不明显,胞质少,胞突纤细。例1、2、3可见胶质区呈毛细胞型星形细胞瘤样形态,其中例2、3见透明玻璃变的血管壁;例4部分胶质区可见少突胶质细胞瘤样形态;例4可见复杂的肾小球样血管,但细胞无明显异型性,胞核级别低,核分裂未见,无坏死。免疫表型:5例Syn在菊形团神经毡处均阳性,菊形团神经细胞Olig-2、S-100和ATRX均阳性,2例部分神经细胞NeuN阳性;5例胶质区GFAP、Olig-2和ATRX均阳性,4例S-100蛋白阳性;5例IDH1均阴性;Ki-67增殖指数<2%,其中例4球样血管增生区Ki-67增殖指数约10%。4例行PIK3CA分子检测,其中1例9号外显子(p.E545K)突变。结论RGNT是一种生长缓慢、罕见的肿瘤,有独特的组织形态,偶有恶变,目前以手术完整切除为主要治疗方法,但同时警惕潜在恶变危险,术后密切随访。     

Secretion of interleukin-6 and vascular endothelial growth factor by spindle cell sarcoma complicating Castleman's disease (so-called 'vascular neoplasia')

So-called 'vascular neoplasia' (VN) is a rare tumour of unknown origin that complicates hyaline vascular type Castleman's disease (CD). This paper reports a case of VN complicating CD of hyaline vascular type, in which neoplastic cells were shown to secrete interleukin-6 (IL-6) and vascular endothelial growth factor (VEGF). In this case, VN first occurred in the retroperitoneum of a 60-year-old male. The lesion showed typical morphology, with three distinct areas: (1) a lymph node-like area with regressively transformed lymph follicles showing hyaline vascular changes and with a hypervascular interfollicular region filled with slit-like vascular channels; (2) an area composed of spindle cell sarcoma; and (3) an area showing angiolipomatous hamartoma. A proportion of the cells in the spindle cell area showed severe pleomorphism. Subcutaneous recurrence after 8 months was composed purely of pleomorphic spindle cells. A karyotypic analysis of the recurrent tumour showed 47, XXY with some instability. Supernatant from primary culture contained high levels of IL-6 and VEGF, suggesting high secretion of these cytokines from neoplastic cells. Immunohistochemically, p53 overexpression was identified only in the pleomorphic spindle cells of the primary lesion and metastatic tumour. No features suggestive of vascular origin were shown on immunohistochemical or electron microscopic analysis of the neoplastic cells. Human herpesvirus type 8 was not detected by immunohistochemistry or PCR analysis. High levels of IL-6 and/or VEGF have been reported to play a role in CD. This is the first case report that clarifies the site of such cytokine production, showing the possibility of CD as a paraneoplastic phenomenon.