Myoid angioendothelioma of the spleen

Although vascular neoplasms of the spleen are rare, they are the most common nonhemopoietic proliferation of the organ, and include hemangiomas, lymphangiomas, hamartomas, littoral cell angiomas, hemangioendotheliomas, and angiosarcomas, as well as the recently described myoid angioendothelioma (MA). MA is an uncommon, benign tumor of the spleen, which is morphologically characterized by a composite of vascular spaces and stromal cells with myoid features. In 1999, in the only report of this unusual neoplasm, Kraus and Dehner described the features of 3 cases. We present another case of MA of the spleen occurring in a 51-year-old man that demonstrated the characteristic morphologic and immunohistochemical features of this neoplasm. In addition to the features described by Kraus and Dehner, our case also displayed the previously unreported findings of focal spindling of the stromal cells and scattered S100-positive cells in the stroma. The case was further unique in having a central stellate scar. Careful attention to histology, possibly with the aid of immunohistochemistry, should distinguish other splenic neoplasms from MA. Although MA is a morphologically distinct lesion, its histologic spectrum, biological behavior, and relationship to other vascular tumors are yet to be fully discovered. It is hoped that the recognition of further cases, and the use of newer molecular technologies, will help better define the nosological position and implications of the diagnosis of this unusual tumor.     

Microscopic sclerosing angiomatoid nodular transformation (SANT) in an accessory spleen or splenunculus

A 63-year old male underwent a distal pancreatectomy and splenectomy for a solid, slowly enlarging pancreatic nodule. Associated with the pancreatic tail but separate to the spleen several lymph nodes were also sampled. The pancreatic lesion was confirmed to be a completely excised serous cystadenoma. The spleen was normal and one of the sampled “lymph nodes” was in fact, an accessory spleen or splenunculus. The splenunculus measured 0.8 x 0.5 x 0.3 cm and grossly appeared uniformly tan in colour. Microscopic evaluation of the splenunculus revealed a 0.4 x 0.3 cm well circumscribed nodule that was clearly demarcated from the rest of the accessory splenic parenchyma. It consisted of a myriad of blood-filled slit-like vascular channels. Within the centre of the lesion a sclerotic, fibrous focus containing similar blood vessels was also noted. The cellular component of ovoid and spindle cells lining the vascular spaces were positive for CD31, CD34 (highlighting a reticular vascular network) and negative for CD8, CD21 and CD68. These features were in keeping with a microscopic sclerosing angiomatoid nodular transformation occurring within an accessory spleen or splenunculus.     

Benign vascular neoplasms of the spleen with myoid and angioendotheliomatous features

AIMS: To present the clinical light microscopic and immunophenotypic features of a distinctive vascular neoplasm of the spleen. METHODS AND RESULTS: Two of the splenic lesions arose in children, and one was found in an adult. They ranged from 19 to 40 mm diameter and histologically were quite similar. Sheets of large epithelioid cells with a spectrum of nuclear configurations ranging from oval and vesicular to twisted and hyperchromatic were noted in each case. Distinct or prominent nucleoli were present in many cells, and occasional cells had nuclear pseudoinclusions. In two cases, bands of basophilic, fibroblast-rich stroma with scattered chronic inflammatory cells were present. The mitotic rate ranged from 0/10 high-power fields (HPF) to 0.5/10 HPF in these epithelioid cells. The vascular nature of these tumours was manifested as a sieve-like array of round, erythrocyte-filled spaces, most with attenuated and cytologically bland lining cells. The polygonal, epithelioid cells exhibited the following phenotype: smooth muscle actin (SMA)+, muscle specific actin (MSA)+, vimentin+, CD31-, CD34-, CD21-, CD8-, CD68- (2/3 cases), S100-, while the lining cells were CD34+, vimentin+ and SMA-, with variable CD31 and factor VIII related antigen expression. Elongated SMA+, MSA+ cell processes were evident in one case, reminiscent of previously characterized myoid elements of the normal spleen. An uneventful follow-up was noted for all three patients. CONCLUSIONS: The histology and immunophenotype set these neoplasms apart from classic hamartomas, haemangiomas and previously characterized (haem)angioendotheliomas of the spleen, and may represent proliferations of myoid elements native to the spleen.     

CD30 and Epstein–Barr virus RNA expression in sclerosing angiomatoid nodular transformation of spleen

Sclerosing angiomatoid nodular transformation (SANT) is a splenic lesion composed of angiomatoid/vascular nodules surrounded by hyalinized/sclerotic stroma, fibroblasts, myofibroblasts, and inflammatory cells. The endothelium within the nodules has a phenotype resembling splenic sinusoids, capillaries, and small veins. Martel et al. (Am J Surg Pathol 28:1268–1279, 2004) suggested that SANT may represent the final pathway of a variety of splenic lesions including inflammatory pseudotumors (IPTs). Epstein–Barr virus (EBV) has a role in the genesis of some splenic IPTs, but its presence in SANT has not been investigated. Six cases of SANT are reported. All were stained for CD31, CD34, CD8, CD68, smooth muscle actin, muscle-specific actin, and CD30 and were tested for EBV by in situ hybridization (EBER). All cases showed angiomatoid nodules with complex expression of CD31, CD34, and CD8, with focal CD68. Expression of CD30 by endothelial cells was also seen. One case had small diffuse areas lacking nodules resembling an IPT and was positive for EBV. The inflammatory cells and the normal spleen were negative for CD30 and EBER. In conclusion, SANT shows upregulation of CD30 with respect to normal spleen. The presence of EBV in the stromal cells of a case supports the notion that a subset of SANT may be related to IPT.     

Sclerosing angiomatoid nodular transformation of the spleen

Sclerosing angiomatoid nodular transformation (SANT) is a recently recognized nonneoplastic vascular lesion of the spleen with fewer than 30 cases described. Microscopically, SANT consists of multiple well-circumscribed vascular/angiomatoid nodules showing plump endothelial cell and extravasated erythrocytes. The nodules are surrounded by a variable lymphoplasmacytic infiltrate, spindle cells, and collagenous stroma. The vascular nodules display a complex mixture of endothelial phenotypes resembling splenic sinusoids (CD34-/CD31+/CD8+), capillaries (CD34+/ CD31+/CD8-), and small veins (CD34-/CD31+/CD8-). Focal expression of CD68 can also be seen. The differential diagnosis of SANT includes splenic hamartoma, inflammatory myofibroblastic tumor, littoral cell angioma, and hemangioendothelioma. It has been postulated that SANT represents a peculiar hamartomatous transformation of splenic red pulp in response to an exaggerated nonneoplastic stromal proliferation. SANT has a benign clinical course with splenectomy being curative.     

Primitive myxoid mesenchymal tumor of infancy: report of two cases and review of the literature

Primitive myxoid mesenchymal tumor of infancy is a recently recognized soft tissue tumor with only a few cases reported. Here, we reported another two cases of the lesion, a 5-month-old boy presenting with a soft tissue mass in the neck region that recurred 2 months later and a 3-day-old girl with a congenital superficial dorsal lumbar mass that extended to the spinal canal 1 month later. They shared similar histological patterns, such as unusual diffuse myxoid background, delicate vascular network, small cystic spaces, low to moderate cellularity, and primitive mesenchymal tumor cells. Immunohistochemically, the tumor cells showed positive for vimentin, CD99, CD117 and nestin, negative for myoid, lipoblastic, histiocytic, and neural markers. In conclusion, primitive myxoid mesenchymal tumor of infancy is a distinctive entity with its own clinical pathological features. Expression of CD99, CD117 and nestin may be consistent with the primitive nature of the tumor and may serve as ancillary markers for differential diagnosis from the other infantile tumors.     

Intravascular myopericytoma: an interesting case of a long-standing large, painful subcutaneous tumor

Myopericytoma is a benign neoplasm consisting of cells that appear to have a distinct differentiation towards presumed perivascular myoid cells. Amongst myopericytoma, an intravascular variant appears to have been reported only rarely. A 67-year-old man presented with a 15-year history of a painful, slow growing 3 × 3.5 cm sized mass in the subcutis of his right lateral thigh. Histopathological studies showed a subcutaneous mass entirely within the lumen of a vein. The tumor was composed of spindle-shaped myoid-appearing cells in a concentric arrangement, intimately associated with thin-walled vascular channels. Tumor cells were diffusely positive for smooth muscle actin, focally positive for CD34, and negative for desmin and CD31. From these findings, we diagnosed this lesion as intravascular myopericytoma. Unlike previous reports, our case showed a relatively large painful subcutaneous mass, although this tumor has an intravascular nature.     

Rapidly-growing nodular pseudoangiomatous stromal hyperplasia of the breast: case report

Pseudoangiomatous stromal hyperplasia is a benign proliferative lesion of the mammary stroma that rarely presents as a localized mass. Pseudoangiomatous stromal hyperplasia is characterized by a dense, collagenous proliferation of the mammary stroma, associated with capillary-like spaces. Pseudoangiomatous stromal hyperplasia can be mistaken with fibroadenoma on radiological examination or with low-grade angiosarcoma on histological examination. Its main importance is its distinction from angiosarcoma. The presented case was a 40-year-old woman who was admitted with a rapidly growing breast tumor. Physical examination revealed an elastic-firm, well-defined, mobile and painless mass in her right breast. Mammograms revealed a 6.7 x 3.7 cm, lobulated, well-circumscribed mass in her right breast but no calcification. Sonographic examination showed a well-defined and homogenous mass, not including any cyst. Based on these findings, a provisional diagnosis of fibroadenoma was made. Considering the rapid growth history of the mass, tumor excision was performed. The excised tumor was well demarcated and had a smooth external surface. Histological examination revealed the tumor to be composed of markedly increased fibrous stroma and scattered epithelial components (cystic dilatation of the ducts, blunt duct adenosis). The fibrous stroma contained numerous anastomosing slit-like spaces. Isolated spindle cells appeared intermittently at the margins of the spaces resembled endothelial cells. Immunohistochemical staining showed that the spindle cells were positive for CD34 and negative for Factor VIII-related antigen. The lesion was diagnosed as nodular pseudoangiomatous stromal hyperplasia.     

Isolated diffuse hemangiomatosis of the spleen: case report and review of literature

Small localized hemangiomas are common neoplasms of the spleen. Isolated diffuse splenic hemangiomatosis, however, is very rare. This lesion can be accompanied by severe hypersplenism and other complications. We report on a case with significant splenomegaly caused by diffuse hemangiomatosis, which was an incidental finding without any clinical disorders. After splenectomy, the normal parenchyma was found to be widely replaced by multiple spongy nodules. Histologically, cavernous vessels were distributed throughout the whole organ, with endothelial cells expressing vimentin, factor VIII and CD 31, but not CD8. Splenic sinus lining cells exhibited a strongly positive reaction with CD8, which became faint and disrupted in highly dilated sinuses in the vicinity of cavernous vessels. In some areas, there seemed to be a gradual transition from cystically dilated splenic sinuses to cavernous vessels. The differential diagnosis must consider other splenic vascular tumors, such as littoral cell angioma, lymphangioma, peliosis of the spleen, and hamartoma. The pathogenesis of diffuse splenic hemangiomatosis is controversial, and a malformative or neoplastic origin is under debate. A derivation from splenic sinusoidal cells was suggested by some authors, but was rejected by others. Our findings cannot exclude a neoplastic origin from splenic sinuses but, finally, the etiology and pathogenesis of this vascular lesion remain uncertain.     

脾脏窦岸细胞血管瘤临床病理观察

目的研究脾脏窦岸细胞血管瘤（LCA）的临床病理及免疫表型特征,探讨脾脏窦岸细胞血管瘤的本质。方法对17例脾脏LCA进行了回顾性研究,包括临床表现、影像学和病理形态学等,并进行了多种抗原标记的免疫表型检测,以正常脾脏、淤血性脾肿大、脾海绵状血管瘤病例作为对照。结果（1）17例脾脏LCA有相似的临床及影像学表现,即脾脏肿大伴单发或多发占位性病变。5例伴肝囊肿,1例伴卵巢浆液性囊腺瘤。（2）大体病理改变为脾脏体积不同程度增大,切面见单个或多个暗褐色结节,结节的直径为0．2～6．0cm不等。（3）镜下改变主要为病变由相互吻合的窦状腔隙组成,腔隙常形成乳头状突起或呈囊性扩张,其中可见两类细胞,一类是衬在腔隙内表面的体积较小的细胞,形似窦岸细胞;另一类是脱落于窦状腔隙内的大细胞,两类细胞均无明显异型性。（4）免疫表型检测：17例标本中的小细胞均呈CD31、多克隆第八因子相关抗原阳性,CD34阴性,1例呈CD8阳性,1例呈CD21阳性,均不表达组织细胞分化抗原;大细胞均表达各种组织细胞抗原,包括CD68（KP1和PG-M1）、CD163和溶菌酶等,各例中均有少数大细胞表达CD31抗原,但均不表达CD34,且相关抗原的表达模式与对照组的三类脾脏良性病变有所不同;大、小细胞均不表达S-100蛋白。结论脾脏窦岸细胞血管瘤是一种良性病变,可能是由于某种原因导致局部血流动力学的改变,致脾脏窦岸细胞增生,脾血窦扩张并相互吻合而形成的局部血管瘤样病变伴组织细胞反应。特征性的形态学改变以及CD31和组织细胞相关抗原的检测有助于该疾病的病理诊断。     

Splenic lymphangioma with papillary endothelial proliferation: a case report and review of the literature

A 76-year-old man complained of difficulty breathing. A solitary mass was found in the spleen by ultrasonography and the tumor was excised. Grossly, the tumor was 3.9 x 2.9 cm in size, solid and brownish in color. A stellate scar-like fibrosis was observed in the center of the tumor. Histologically, the tumor consisted of the proliferation of irregular and small lymph vessel-like spaces, with sclerotic change in the center. The lymph vessel-like spaces showed papillary projections of the lining cells. The lumen contained amorphous proteinaceous fluid. Immunohistochemically, the lining cells of lymph vessel-like spaces were positive for endothelial markers (CD31, CD34, factor VIII-related antigen), and bound Ulex europaeus agglutinin-1. The tumor was diagnosed as splenic lymphangioma, but its appearance was rather unusual for a typical splenic lymphangioma because of the presence of papillary endothelial proliferation and scar-like fibrosis. Splenic lymphangioma with papillary endothelial proliferation is uncommon, and there have been only four cases reported.     

Gastrointestinal stromal tumor colliding with angiosarcoma

The collision of gastric tumors is rare, and those involving gastrointestinal stromal tumor and angiosarcoma have not been previously reported. This article reports a gastric tumor involving collision of gastrointestinal stromal tumor and angiosarcoma. The patient was an 81-year-old man who presented with dyspepsia and large gastric mass. The mass showed a proliferation of spindle cells expanding the muscularis propria. Most of the tumor consisted of spindle cells with low-grade cytology that were positive for CD117 (c-kit), indicating gastrointestinal stromal tumor. Occasional prominent foci showed dissecting and anastomosing channels of ectatic vascular spaces lined by cytologically malignant cells that were positive focally for CD117 and diffusely positive for multiple vascular markers, indicating angiosarcoma.     

A case of cord capillary hemangioma of the spleen: A recently proven true neoplasm

Cord capillary hemangioma (CCH) of the spleen is an extremely rare lesion. Once classified under splenic hamartoma, CCH is now differentiated from hamartoma, as its clonality has recently been proven. Herein, we present the case of an incidentally found CCH, measuring 6 × 5.5 × 5 cm, in a 45‐year‐old man. He underwent splenectomy and has been recurrence‐free for 8 years. Macroscopically, the cut surface of the mass showed a central stellate scar with peripheral interspersed reddish areas of variable sizes and intervening fibrous bands. Microscopically, the mass was well demarcated from the splenic tissue. The macroscopic reddish areas were found to correspond to nodules of various sizes, which were predominantly composed of CD34‐expressing capillaries without the presence of CD8‐expressing sinuses. The relative proportion of these two types of vessels distinguishes CCH from sclerosing angiomatoid nodular transformation (SANT), as SANT shows the apparent presence of CD8‐expressing sinuses. In longstanding cases of SANT, sinuses might become ambiguous and the differences between CCH and SANT might become subtle. Nonetheless, immunohistochemistry should be performed when these conditions are suspected, since accurate distinction is usually achieved as a result.     

骨髓基质细胞的造血支持作用等生物学特性的研究

目的研究人骨髓基质细胞体外长期培养的生物学特性和造血支持功能。方法①采用静置贴壁细胞培养法,体外长期培养胎儿、儿童和成人的骨髓基质细胞。②采用免疫细胞化学染色法和流式细胞仪检测法,分析细胞的表型。③将不同发育阶段的骨髓基质细胞体外培养,并扩增脐血造血干细胞。结果①建立了成纤维肌样细胞系,可传至10代,维持6个月,同时还培养出内皮细胞和巨噬细胞。②儿童骨髓基质肌样细胞的染色特征为波形纤维蛋白(viementin)呈阳性,第VIII因子呈阴性;儿童骨髓基质细胞的表型为CD33     

Low-grade B-cell lymphomas of the splenic marginal zone: a clinicopathological and immunohistochemical study of 14 cases

We have studied 14 cases of low-grade, splenic marginal zone, B-cell non-Hodgkin's lymphoma. The clinical presentation in all cases was with splenomegaly and, in 10 cases, circulating neoplastic lymphoid cells in the peripheral blood with involvement of bone marrow. In all cases the splenic white pulp was hyperplastic with expansion of marginal zones and varying degrees of infiltration of germinal centres by neoplastic cells. The cells were a mixture of medium sized lymphocytes with moderate amounts of cytoplasm and finely dispersed nuclear chromatin, together with occasional blast cells with small nucleoli. Satellite red pulp aggregates of tumour cells centred on small epithelioid cell clusters were seen in all cases. These appear to be a characteristic and diagnostically important feature of splenic marginal zone lymphoma. The tumour cells expressed CD20, CD45RA, bcl-2 and the antigens detected by MB2. All cases expressed IgM with light chain restriction. In addition, IgD was expressed in four cases. The follicular dendritic cell network was disrupted in those follicles which were infiltrated by tumour cells. A network of stromal myoid cells, at the periphery of the marginal zone, identified by expression of α-smooth muscle actin, was preserved. Alpha-smooth muscle actin positive dendritic cells were also seen within and around satellite tumour nodules in the red pulp.     

Myoid gonadal stromal tumor: a distinct testicular tumor with peritubular myoid cell differentiation

We report a distinct, primary testicular tumor with peritubular myoid cell differentiation. A 25-year-old man developed a well-circumscribed testicular tumor composed of cytologically bland spindled cells, which were strongly and diffusely positive for desmin, smooth muscle actin, muscle-specific actin, and smooth muscle myosin. In addition, S-100 was diffusely positive, and cytokeratin (CK5/6 and AE1/3) was focally positive. Calretinin, inhibin, and CD34 were all negative. This pattern of immunoreactivity was very similar to the normal adjacent peritubular myoid cells. Follow-up after radical orchiectomy showed benign behavior. We found reports of 6 similar intratesticular tumors demonstrating peritubular myoid cell-like differentiation and having favorable outcome. We believe that the myoid gonadal stromal tumor is a rare, yet distinct, testicular tumor separate from leiomyoma and deserves recognition.     

脾脏硬化性血管瘤样结节性转化病理形态观察

目的探讨脾脏硬化性血管瘤样结节性转化的临床病理表现及诊断、鉴别诊断。方法对4例脾脏硬化性血管瘤样结节性转化进行常规HE及免疫组织化学（EnVision法）观察并结合文献讨论。结果脾脏硬化性血管瘤样结节性转化的最大特征是在纤维硬化间质中形成多个血管瘤样结节。结节为单个或多个融合,周围为增生纤维组织包绕。结节中央可见裂隙样或不规则形或略为扩张的血管腔构成,内衬肿胀的内皮细胞。血管腔隙之间为梭形细胞和卵圆形细胞。免疫组织化学显示结节内为CD34阳性表达的小血管及少量CD8阳性表达的窦性腔隙,CD31阳性表达的内皮细胞数量多,并构成复杂的网状结构,局灶性内衬细胞CD68亦为阳性,平滑肌肌动蛋白阳性细胞成簇分布在血管腔隙之间,结节间梭形细胞局灶性肌动蛋白阳性,但结蛋白、CD21、CD35阴性。结论脾脏硬化性血管瘤样结节性转化是一种少见的良性病变,有其特征的临床病理表现,应注意与脾脏其他类型肿瘤及瘤样病变鉴别。     

Two splenic lesions in need of clarification: hamartoma and inflammatory pseudotumor

This short review is dedicated to a precise pathologic characterization of 2 uncommon and poorly defined lesions of the spleen and to their distinction from histologically similar processes. Splenic hamartoma represents an abnormally formed red pulp and is characterized by the presence of sinus-like structures lined by CD8(+) endothelia. The great variety of its morphologic appearances may result from the preponderant growth of one or another of the several components of the red pulp, ie, CD34(+) capillaries, myoid cells and macrophages. Therefore, it is proposed that "cord capillary hemangioma," myoid angio-endothelioma, and histiocyte-rich tumors are part of the spectrum of splenic hamartoma. Inflammatory pseudotumor (IPT) of the spleen is a reactive lesion, probably of multiple etiologies, characterized by a mixture of inflammatory cells and a minor, disorganized component of spindle cells. The latter include fibroblasts, SMA(+) myofibroblasts, and CD68(+) spindled histiocytes, establishing a close similarity with the IPT of the lymph node. This benign process needs to be distinguished from 2 others that have a predominant spindle cell component arranged in parallel bundles: the IPT-like follicular dendritic cell tumor, which is consistently associated with Epstein-Barr Virus; and the inflammatory myofibroblastic tumor, also often Epstein-Barr Virus-related and similar to those of the soft tissues, lung and other organs. These 2 lesions are neoplastic and therefore have a potentially worse prognosis than IPT.     

Splenic marginal zone lymphoma in a European harvest mouse (Micromys minutus)

A splenic marginal zone lymphoma was diagnosed in a female European harvest mouse (Micromys minutus) that presented clinically with poor body condition and abdominal swelling. On palpation, a mass in the cranial abdomen was identified. The owner elected euthanasia. Necropsy revealed a markedly enlarged spleen, which was uniformly pale red. Histological examination of the spleen revealed monomorphic sheets expanding from the marginal zone composed of large polygonal to oval cells containing abundant finely granular eosinophilic cytoplasm. No abnormalities were noted in any other organs. Immunohistochemical evaluation of the tumor cells demonstrated positive staining for CD45R and IgM and negative staining for CD4, CD8 and IgD. The diagnosis of splenic marginal zone lymphoma was based on the anatomical location, the lack of involvement of other organs and the histological and immunohistochemical findings.