Ultrastructural Diagnosis of Histologically Atypical Idiopathic Thrombocytopenic Purpura

The histologic and electron microscopic findings in the spleen of a 61-year-old white man with corticosteroidunresponsive idiopathic thrombocytopenic purpura (ITP) are described. Light microscopically, the spleen lacked features characteristic of ITP, such as germinal centers and foamy histiocytes. Ultrastructurally, however, platelet phagocytosis, which is diagnostic of this entity, was readily demonstrable in splenic cord macrophages.     

Unusual vascular changes in the red pulp of the spleen accompanying breast carcinoma metastasis

The prevalence of splenic metastasis from carcinomas varies between 2% and 13% in autopsy studies. Most of them are clinically inapparent. We report herein the case of a splenic metastasis revealing breast carcinoma in a 73-year old woman. Splenectomy was performed to correct hypersplenism. Macroscopically, the cut surface of the spleen was uniform and pale. On microscopical examination, the metastatic infiltration involved both red and white pulp as single cells, cords and micro-nodules. Tumor cells were positive for cytokeratin and epithelial membrane antigen (EMA). The breast origin of this splenic metastasis was supported by the increase of CA 15-3 level, and by the appearance of axillary lymphadenopathy. In addition, the red pulp sinuses were obliterated by multiple thrombi at different stages of development and the splenic cords were collagenized. These changes could result from an unusual stromal reaction.     

肝移植患者围手术期骨髓细胞学改变的意义

背景：晚期肝病及肝移植后造血系统受累相关报道较少见。 目的：通过对肝移植患者围手术期骨髓细胞学的观察,探讨移植前造血功能的改变及移植后多种并发症对骨髓造血功能的影响。 方法：选择20例实施原位肝移植患者,因与血液系统疾病相关,需行骨髓细胞学检查进行诊断及鉴别诊断,其中移植前2例,移植后18例。 结果与结论：原位肝移植患者移植前容易出现骨髓细胞学改变为脾功能亢进、大红细胞性贫血,移植后出现：移植物抗宿主病、浆细胞白血病、反应性粒细胞增高、原发性血小板减少性紫癜、嗜血细胞综合征、粒细胞缺乏症、急性造血细胞停滞、转移癌、反应性血小板增高。说明通过骨髓细胞学检查,监测肝移植围手术期各种并发症对骨髓造血功的影响,特别对移植物抗宿主病的患者,实施及时抢救有重要意义。     

Metastatic tumors to the spleen: a 25-year clinicopathologic study

OBJECTIVE: The clinicopathologic features of splenic metastases have seldom been investigated. The aim of this study was to evaluate the clinical and pathological impact of splenic metastases. CASE MATERIAL: We reviewed the clinical/autopsy records and pathologic features of 92 Chinese patients (58 men, 34 women) with secondary nonlymphoid splenic tumors recorded during a 25-year period. RESULTS: The incidence of splenic secondary tumors at autopsy was 0. 6% and at splenectomy, 1.1%. The lesions were often seen in elderly patients (mean age, 60 years). Seven (8%) of the splenic lesions were symptomatic. The symptomatic splenic lesions, as compared with asymptomatic lesions, were bigger and were found more often in women and younger patients. Two patients experienced spontaneous splenic rupture because of metastatic carcinoma. Eighty-seven (95%) of the secondary splenic tumors were carcinomas. Lung was the most common primary tumor site (21%), followed by the stomach (16%), pancreas (12%), liver (9%), and colon (9%). Rarely reported sources of primary tumor, such as esophageal carcinomas, nasopharyngeal carcinoma, and choriocarcinoma, were also found. Splenic metastases could be identified macroscopically in 74 (80%) of our patients. Grossly, splenic metastases involved the splenic capsule (n = 8) or were solitary (n = 31), multiple (n = 30), or diffuse (n = 8) lesions in the splenic parenchyma. Isolated splenic metastases were noted in 5.3% of the metastases found at autopsy. Many of the metastatic lesions in the spleen were identified shortly after primary tumors were detected (mean latent period, 6.7 months). The time from diagnosis of the primary tumor to metastasis to the spleen was more than 2 years in 14 patients. CONCLUSIONS: Splenic metastases are uncommon. A variety of clinical and pathologic patterns were noted in our series.     

Ureteral obstruction from metastatic breast carcinoma.

Metastases from carcinoma of the breast may involve one or both ureters, and may be a clinically important phenomenon. Two cases are presented and the autopsy experience with 181 cases of metastatic breast carcinoma is reviewed. Ureteral involvement was demonstrated in 8.3% of the cases. Bilateral metastases were common.     

Severe thrombocytopenia secondary to asymptomatic cytomegalovirus infection in an immunocompetent host.

A healthy 33 year old man presented with a short history of purpura and easy bruising. Investigations showed profound thrombocytopenia with atypical lymphocytes in the peripheral blood. Marrow appearances were consistent with platelet consumption. Biochemical hepatitis was also noted. An infection screen showed the underlying diagnosis to be cytomegalovirus (CMV) infection. He was treated successfully with oral prednisolone. This subsequently tailed off without relapse. Careful examination of a stained blood film is needed in all cases of apparent idiopathic immune thrombocytopenic purpura.     

Splenic histiocytosis in idiopathic thrombocytopenic purpura: A relative sphingomyelinase deficiency?

The case of a patient in whom idiopathic thrombocytopenic purpura (ITP) was associated with diffuse splenic histiocytosis is described; the patient's subsequent sphingomyelinase level was at the lower limits of the normal range. The patient's splenic lecithin:sphingomyelin ratio was not significantly different from that of 11 age-matched control subjects. It is postulated that the sporadic cases of splenic histiocytosis in patients with ITP are due to a relative, acquired sphingomyelinase deficiency.     

Angiosarcoma of the spleen clinically presenting as metastatic ovarian cancer. A case report and review of the literature

Primary angiosarcomas of the spleen are rare and almost always fatal. With no more than 200 cases reported in the literature worldwide, no specific risk factors are strongly associated with the disease. The mean age of patients at presentation is 59 years and the major clinical findings include abdominal pain, splenic rupture, and splenomegaly. Grossly, this neoplasm appears as hemorrhagic and/or cystic nodules, with a low-density signal seen on computed tomographic scans. Histologically, the tumor is characterized by neoplastic proliferation with diffuse or focal areas of a vasoformative component with cavernous and arborizing channels. The vascular spaces are lined by endothelial cells with variable degree of atypia. The differential diagnosis includes a variety of benign and malignant vascular proliferations (littoral cell angioma and Kaposi's sarcoma) as well as metastatic tumors. The worst prognostic factor is splenic rupture with early metastasis. The liver is the most common site. We report a case of the 43-year-old woman with a long-standing history of recurrent ovarian carcinoma treated with surgery and multiple courses of radiation therapy and chemotherapy who clinically appeared to have a metastatic ovarian cancer to the spleen and treated with partial resection of stomach and splenectomy. However, histopathologic examination of the specimen showed the tumor to be of a primary angiosarcoma. We believe that the lengthy exposure to radiation may have played a role in the histopathogenesis of this neoplasm in this patient.     

Size of spleen rather than amount of platelet sequestration may determine long term responses to splenectomy in adult idiopathic thrombocytopenic purpura.

Fourteen adults with idiopathic thrombocytopenic purpura suffered a relapse after treatment with steroids, vinca alkaloids, or intravenous gammaglobulin. Splenic sequestration of platelets labelled with 111In-oxine was assessed, and the patients then underwent splenectomy. During follow up of four to 47 months (mean 20.7) none of the patients required further treatment, including three of 14 who showed partial relapses. Splenic sequestration patterns did not predict relapses, but an unexpected finding was that patients who relapsed had significantly smaller spleens. It is concluded that splenectomy is beneficial in most adult patients with idiopathic thrombocytopenic purpura and that radiological techniques to measure the size of the spleen may be useful in predicting which patients may relapse.     

The indirect platelet suspension immunofluorescence test in the detection of platelet antibodies in idiopathic thrombocytopenic purpura.

Among the various techniques developed for the detection of platelet antibodies, the platelet suspension immunofluorescence test has been reported to be simple, sensitive and reproducible, and therefore more clinically useful than other techniques available. An initial evaluation of the test was carried out for the detection of platelet autoantibodies in ten cases of idiopathic thrombocytopenic purpura. The indirect PSIFT was found to be positive in 60%. The technical aspects of the test and the problems encountered are discussed.     

Splenic pathology in immune thrombocytopenia.

Splenic pathology was analysed in 73 patients with immune thrombocytopenic purpura who underwent splenectomy for bleeding that had been resistant to adrenocorticosteroids. The mean splenic weight was 100 g. The only notable macroscopic feature was the prominence of Malpighian corpuscles in 15 cases. Microscopic examination showed formation of germinal centres in the lymphoid tissue of the white pulp in 40 cases, prominence of the histiocytes in the red pulp in 18 cases, and infiltration with neutrophils in the same area in 49 cases. Myeloid metaplasia throughout the splenic tissue was minimal in 58 cases, moderate in 15, and extreme in two. No distinguishing features were found in the spleen from patients who had not received previous immunosuppressive treatment (n = 3), those treated with prednisone (1 mg/kg/day) for a median of 14 days (n = 62), or those who had received the same dose of prednisone and additional azathioprine or cyclophosphamide (2 mg/kg/day) for a median of four weeks (n = 8). No correlation could be shown between histological features and the age of the patient or titre of antiplatelet antibodies. Similarly, no distinguishing features were found in patients with associated systemic lupus erythematosus (n = 8), hyperthyroidism (n = 6), immune haemolysis (n = 3), or recent viral illness (n = 3).     

The pathology of the spleen in steroid-treated immune thrombocytopenic purpura

The spleen is a central organ in the pathophysiology of immune thrombocytopenic purpura (ITP). Splenic lymphoid tissue synthesizes anti-platelet IgG, and splenic cordal macrophages destroy platelets coated with anti-platelet antibodies. The morphologic features of the spleen in this disease reflect this splenic function: hypertrophied lymphoid follicles with secondary germinal centers in the white pulp, with perivascular plasma cells in the red pulp and evidence of increased platelet phagocytosis in cords of the Billroth. Foamy macrophages and evidence of a variable degree of extramedullary hematopoiesis also have been noted. The authors have studied 17 spleens removed for therapeutic purposes in patients with proven ITP previously treated with varying amounts of corticosteroids. In all cases there was little or no morphologic evidence of follicular hyperplasia or plasmacytosis. However, platelet sequestration and phagocytosis were demonstrated easily in all cases, both in histologic sections and in touch imprints. The authors' findings indicate that morphologic evidence of lymphoid activation characteristic in spleens from patients with ITP usually is ablated by prior corticosteroid therapy but that the characteristic platelet sequestration and phagocytosis persists.     

The splenic red pulp; a histomorphometrical study in splenectomy specimens embedded in methylmethacrylate

The anatomy and pathology of the splenic red pulp was studied in three-dimensional reconstructions of methylmethacrylate embedded blocks of tissue obtained after splenectomy, as well as by morphometrical analysis of a large number of specimens. The sinuses of the spleen form a plexus of anastomosing vessels with remarkable buds. Capillaries end as sheathed capillaries in the cord tissue, the 'filtering' area, but a large proportion of the red pulp cords appear to be 'non-filtering'. These might form part of the lymphatic compartment, which is separate from the white pulp and its extension along the capillaries. This area has not yet been described in man. The change in the volume and structure of the various components of the red pulp were studied in 60 controls and in cases of traumatic rupture, idiopathic thrombocytopenic purpura, aplastic anaemia, autoimmune haemolytic anaemia, congenital spherocytosis, splenic congestion, and Hodgkin's disease. Significant differences were found in the volume of filtering and non-filtering areas, the size of the sinus compartment, and the degree of vascularization; these differences were only partially expected, for instance in disorders with excessive erythrocyte sequestration. A decrease of the 'non-filtering' area in Hodgkin's disease might indicate an unknown aspect of this disease. In agreement with our previous paper on the amount of white pulp, spleens removed because of traumatic rupture and those incidentally removed during abdominal surgery may not be combined as a single control group, because of significant and probably functional differences in the composition also of the red pulp.     

Solitary splenic metastasis of an adenocarcinoma of the lung

Splenic metastasis of solid tumors is a rare event, most often diagnosed at the time of autopsy. Whereas in cases of widely disseminated cancer, splenic involvement may be fairly common, solitary splenic metastasis in the absence of other metastases is exceedingly rare. The authors report a case of a 63-year-old woman in whom the sole detectable distant metastasis of a lung carcinoma was a splenic mass. The splenic lesion was detected before the resection of the primary lung lesion during a complete metastatic work-up. At that time, however, it was considered unlikely that the mass in the spleen represented a metastasis because of the lack of metastatic disease elsewhere.     

脾脏转移癌的临床病理特点

目的探讨脾脏转移癌的临床病理特点及其转移规律。方法总结16例脾脏转移癌病例,复习临床、外检、尸检记录资料,对其性别、年龄、临床症状、原发部位、组织学类型、脾脏的大体特点、脾脏内肿瘤的生长方式进行了分析。结果16例脾脏转移癌中,男性12例,女性4例;男性显著多于女性;年龄范围从48岁到90岁,其中位年龄为66．5岁;临床症状主要表现为左上腹不适,疼痛,消瘦乏力,食欲不振等,有些病例可扪及脾肿大,CT可发现脾内占位。肺是脾脏转移癌的最主要的原发部位,占总例数的43．8％（7／16）;男性最常见的原发部位是肺,占50．0％（6／12）,而女性最多见的是卵巢（2／4）。组织学类型中,肺未分化癌是最多见的类型,占25．0％（4／16）,其中小细胞未分化癌3例,大细胞未分化癌1例;其他依次为：肺细支气管肺泡癌2例;结肠腺癌2例;卵巢浆液性乳头状囊腺癌2例;前列腺腺癌2例。男性最多见的类型是肺未分化癌,而女性为卵巢浆液性乳头状囊腺癌。脾脏转移癌的生长方式分为单结节性、弥漫性和多结节性3种类型,多数肿瘤表现为单结节性的生长方式,少数高转移潜能的肿瘤（5／16）表现为弥漫性和多结节的生长方式,包括肺小细胞未分化癌（3／3）,肺腺癌（1／1）和前列腺腺癌（1／2）。结论脾脏转移癌少见,掌握其临床病理形态特点对于病理诊断和临床处理有指导意义。     

Isolated splenic metastasis from carcinoma of the breast: A Case Report

Breast carcinoma with visceral metastasis to the lungs, liver, and bone is common. However, isolated splenic metastases from breast carcinoma are rare. This has been rarely described in the medical literature. This case report presents a 48‐year‐old woman with newly diagnosed breast cancer and an isolated splenic metastasis diagnosed by ultrasound‐guided fine‐needle aspiration (FNA). Radiologic staging revealed no involvement of other organs, such as lungs, liver, or bone. The pathogenesis of rare single splenic metastasis and the diagnostic role of FNA on the spleen lesion are discussed. This case is being reported due to its rare metastatic initial presentation and the role of FNA in achieving the diagnosis. Diagn. Cytopathol. 2013;41:914–916. © 2012 Wiley Periodicals, Inc.     

Structure of the spleen in idiopathic thrombocytopenic purpura.

The structure of the spleens of 12 patients with idiopathic thrombocytopenic purpura (ITP) who underwent splenectomy was studied. The white pulp was characterized by the presence of large numbers of lymphatic nodules containing highly reactive germinal centers. The marginal zone contained large numbers of vessels surrounded by plasma cells. These findings imply active antibody production and are consistent with the concept that the spleen is a major source of antiplatelet antibody production in ITP. Large numbers of platelets in various stages of degradation were seen in cords, particularly in the marginal zone. They appeared both extracellularly and with the cytoplasm of macrophages. It appeared that platelet destruction was initiated by focal cytoplasmic degradation and resulted in formation of cellular debris. These findings indicate that the spleen plays a fundamental role in the pathogenesis of ITP, involving synthesis of antiplatelet antibody, localization of platelets in a milieu rich in this antibody, and subsequently, phagocytosing of immune-damaged platelets.     

Idiopathic thrombocytopenic purpura with normal platelet survival time

Platelet survival has been measured in 16 patients with idiopathic thrombocytopenic purpura. Of this group, three patients had a normal result and surface counting did not show high splenic uptake. The clinical features of these patients are described. These patients have remained well for several years without treatment.     

Thrombocytopenia in brucellosis: case report and literature review

BACKGROUND: Brucellosis, constituting a major health problem in many parts of the world--particularly in the Mediterranean and the Middle East--is a multisystem disease with a broad spectrum of clinical manifestations. Hematological abnormalities ranging from a fulminant state of disseminated intravascular coagulopathy to subtle hemostatic alterations have been reported in brucella infection. Immunemediated thrombocytopenia is also a clinically important mechanism that can be encountered during brucellosis. CASE: A young lady with fever was referred to a university hospital because of thrombocytopenia. The provisional diagnosis was idiopathic thrombocytopenic purpura, as the bone marrow examination showed an increased number of megakaryocytes and the absence of fever after hospitalization. The patient responded well to corticosteroid treatment. However, she was finally diagnosed with brucellosis with positive bone marrow and blood cultures for B. abortus and agglutination test of 1:320. The patient was discharged from the hospital 10 days later in good health on rifampicin and doxycycline therapy. The follow-up of the patient revealed normal hematological findings together with a progressive reduction in the titer of the agglutination test for brucella. CONCLUSION: Brucella infection may cause severe thrombocytopenia, mimicking a primary hematological disease that is reversible after appropriate antimicrobial therapy. In cases of brucellosis-induced immune thrombocytopenic purpura, a short-term standard dose of corticosteroid treatment might be an alternative and additional treatment as an urgent approach for thrombocytopenia while initiating antibrucellosis treatment.     

Germ cell tumour as a diagnostic pitfall of metastatic carcinoma.

AIM: Testicular germ cell tumours may present as metastases in cervical lymph nodes, yet the primary tumours remain clinically occult. The aim of the study is to alert pathologists and clinicians to this uncommon but important presentation and highlight the clues and the diagnostic adjuncts to its correct diagnosis. METHODS: The clinical, cytological, histological, and immunohistochemical features of two patients with germ cell tumour initially presenting as cervical lymphadenopathy were described and analysed. RESULTS: Both patients were young adult males, who were found to have metastatic undifferentiated carcinoma on fine needle aspiration of the enlarged cervical lymph nodes. The tumour cells in both cases were positive for placental alkaline phosphatase (PLAP) and negative for epithelial membrane antigen (EMA). CONCLUSIONS: Clinicians and pathologists should be aware of the possibility of germ cell tumour when encountering a young adult male with metastatic poorly differentiated carcinoma. Positivity for PLAP and negativity for EMA are helpful adjuncts in arriving at the correct diagnosis.