富于间质透明血管型Castleman病的病理形态、增生间质细胞组织起源和临床并发症关系探讨

目的 对透明血管型Castleman病滤泡间区内间质细胞的病理形态、免疫表型以及组织来源进行深入研究,在此基础上,对间质细胞在疾病形成以及副肿瘤天疱疮发生过程中的作用进行初步探讨.方法 选取透明血管型Castleman病23例,收集详细临床资料,分析组织病理形态,对全部病例进行免疫组织化学染色,抗体有CCL21、肌特异性肌动蛋白(MSA)、CD21、CD35、S-100蛋白和CD34.按照Danon等的标准进行分类,将滤泡间区占淋巴结面积大于50%的病例归入富于间质型,其余为普通型.结果 23例中,富于间质型14例,普通型9例.富于间质型病例伴副肿瘤天疱疮11例,普通型无一例伴副肿瘤天疱疮,两者差异有统计学意义(P<0.01).滤泡间区内间质细胞免疫组织化学染色结果:普通型9例,CCL21、MSA均为阳性,CD21、CD35、S-100蛋白、CD34均为阴性;富于间质型14例,CCL21阳性13例,MSA阳性13例,CD21、CD35、S-100蛋白、CD34均为阴性;组间差异无统计学意义(P>0.05).结论 透明血管型Castleman病在病理上存在普通型和富于间质型两种表现,两者在副肿瘤天疱疮的发生率上存在显著差异.纤维母细胞性网状细胞是透明血管型Castleman病滤泡间区内最主要的间质细胞,其特征性的免疫表型为CCL21~+/MSA~+/CD34~-/CD21~-/S-100~-.富于间质型患者易于伴发副肿瘤天疱疮,可能与纤维母细胞性网状细胞的过度增生有关,详细的机制有待进一步研究.     

Mixed tumours of the skin: a histopathological, enzyme-histochemical and immunohistochemical study

Twenty-eight cases of mixed tumour of the skin were studied and subclassified into three types: eccrine (1 case), indeterminate (7), and apocrine type (20). The indeterminate type was defined as mixed tumours having tubulo-alveolar patterns with two layers of epithelium, but without apocrine secretion or pilosebaceous differentiation. Enzyme-histochemical studies were performed on four cases (one indeterminate, three apocrine): in the indeterminate type the tubular epithelial cells showed eccrine differentiation while in the apocrine type tubules were found showing the direction of differentiation to be toward the apocrine gland, but tubules with eccrine differentiation were intermingled in all three. Immunohistochemically, no differences were observed between the indeterminate and the apocrine type: hints of eccrine features were observed in both groups. Thus, the indeterminate type could be an eccrine tumour and the apocrine type showed direction of differentiation toward both eccrine and apocrine glands. It is concluded that mixed tumours of the skin are fundamentally eccrine neoplasmas, and that the apocrine features may represent apocrine metaplasia.     

Castleman病的临床病理观察

目的 研究Castleman病临床病理学的特点,探讨其鉴别诊断和发病机制。方法 观察26例Castleman病的病理形态,用EnVision两步法对其中20例行CD45RO、CD45RA、CD20,以及κ、λ轻链免疫组织化学染色,结合其临床表现、治疗进行分析,并获得16例的随访资料。结果 临床表现为伴有贫血、血沉快、血清球蛋白异常、肝脾肿大、皮疹以及肺和肾损害,1例因并发肺损害和肾衰竭死亡。病变呈局灶性20例、多中心性6例;透明血管型19例、浆细胞型4例和混合细胞型3例。多中心性包括了4例浆细胞型和2例混合细胞型;局灶性20例中,13例仅有单发淋巴结肿大,且均为透明血管型,预后良好。另7例伴副肿瘤性天疱疮者,有血清球蛋白异常(4／7)及肺脏异常(5／7例),透明血管型6例和混合型1例,伴套区淋巴细胞和树突状网织细胞,小血管和浆细胞增生。术后皮损好转,肺损害无改变。免疫组织化学可见κ和λ两种轻链的表达。结论 Castleman病为淋巴组织增生性疾病,临床和病理上要与多种疾病鉴别,且病理的鉴别尤其重要。它的多器官受累可能与自身免疫疾病的发病机制相似。     

Morpho-immunophenotypic diversity of Castleman's disease,hyaline-vascular type: With emphasis on a stroma-rich variant and a new pathogenetic hypothesis

A histologic review of 102 cases of Castleman's disease of the hyaline-vascular type, with a detailed paraffin immunophenotypic study of 23 of them, was undertaken to evaluate the morphologic variability of this disorder and its immuno/cyto-architectural characteristics. All cases had features in common including: abnormal follicles, with increased vascularity, poorly formed germinal centers and predominance of the mantle zone; lack of sinuses; and hypervascular interfollicular tissue containing large numbers of KP1-positive plasmacytoid monocytes. Networks of actin-positive cells [fibroblastic reticulum cells (RCs) or myoid cells] and KP1-positive dendritic cells (histiocytic RCs) were seen. There were differences in the proportion of follicles to interfollicular tissue, which covered a continuum from a follicular, through a classic, to a stroma-rich variant. The last-mentioned was qualitatively different as it showed loss of HECA-452 and MECA-79 reactivity in the blood vessels, decreased plasmacytoid monocytes and increased myoid cells and histiocytic RCs. In 5 cases there was formation of distinct nodular growths which varied from spindle cell foci to angio-histiocytic-RC proliferations, all of which may be confused with vascular or follicular dendritic RC neoplasms. From our findings, data from the literature and the working hypothesis that plasmacytoid monocytes are the precursors of both follicular dendritic RCs and sinus lining cells (Parwaresch et al.), a pathogenetic theory is proposed for this type of Castleman's disease which postulates that a developmental block in plasmacytoid monocytes results in their accumulation with poor formation of germinal centers and sinuses under stimulation. The lack of sinuses would lead to impaired egress of circulating lymphocytes which, however, would continue to enter the node through functional high endothelial venules and to accumulate in the mantle zone. The factors responsible for angiogenesis and for the cellular growths that characterize the stroma-rich variant remain to be determined, as do the relationships between the three variants.The opinions expressed in this article are the personal views of the authors and are not to be construed as representing the views of the Department of the Army or the Department of Defense.     

Follicular hyperplasia presenting with a marginal zone pattern in a reactive lymph node lesion

Histologically, the marginal zone pattern of the lymph node is characterized by lymphoid follicles with three distinct layers. The inner layer is composed of follicular center zones, the middle layer of darkly stained mantle zones, and the outer layer of marginal zones. However, the marginal zone pattern is rarely seen in reactive lymph nodes except for mesenteric lymph nodes. We describe the clinicopathologic, immunohistochemical and genotypic findings of six cases of reactive follicular hyperplasia exhibiting the marginal zone pattern. The patients comprised three males and three females (age range 24 to 63 years; medium 56 years). Follow-up data were obtained from five patients. None of them developed malignant lymphomas during the follow-up period of from 5 to 204 months (median 68 months). Histologically, the lesion was characterized by numerous lymphoid follicles and partial distortion of lymph node structure. Varying degrees of progressive transformation of the germinal center (PTGC) were noted in the four cases. The marginal zone pattern was observed in some or most of the lymphoid follicles including PTGC. The marginal zone B cells were small to medium-sized lymphocytes with round or slightly indented nuclei and a broad rim of pale cytoplasm. Some of them had a monocytoid appearance. They were CD20+, CD79a+, sIgM+/-, sIgD-, CD5-, CD10-, CD21-, CD23-, CD43-, CD45RO-, Bcl-6-, cyclin D1-, EMA- and p53-. A portion of them were Bcl-2 positive. Occasional large lymphoid cells with round or indented nuclei and moderate amounts of cytoplasm were observed in the marginal zone in four cases. These large lymphoid cells were usually CD20 positive, but Bcl-6 negative. A small number of them contained polytypic intracytoplasmic immunoglobulins. The polytypic nature of B lymphocytes was demonstrated by immunohistochemistry and polymerase chain reaction. Recognition of unusual marginal zone hyperplasia in reactive lymph node lesions is important to avoid confusion with nodal involvement in various low-grade B cell lymphomas presenting a marginal zone distribution pattern.     

Progressive transformation of germinal center presenting with histological features of hyaline-vascular type of Castleman's disease

We report three cases showing progressive transformation of the germinal center (PTGC) with histological features reminiscent of the hyaline-vascular (HV) variant of Castleman's disease (CD). Each case contained a few small HV germinal centers as well as PTGC and hyperplastic germinal centers with or without follicular lysis. Moreover, some of the PTGC were penetrated by hyalinized small vessels. Our three cases also showed some of the characteristic histological findings of HV type of CD: (i) reactive lymphoid follicles with small hyaline-vascular germinal centers surrounded by small lymphocytes in a concentrated fashion; (ii) a few small foci of plasmacytoid monocytes; (iii) perivascular fibrosis; (iv) interfollicular vascularity; (v) tight/concentric pattern of the follicular dendritic cell network; and (vi) absence of CD57+ T-cells in the HV follicles. The PTGC with coexistent HV type of CD may represent a certain form of reactive follicular hyperplasia. The possibility of PTGC should be considered and excluded before diagnosing CD.     

Clinical implications and value of immunohistochemical staining in the evaluation of lymph node infarction after fine-needle aspiration

We report on a series of 3 patients who underwent fine-needle aspiration (FNA) for clinically apparent lymphadenopathy. In all 3 cases, a diagnosis of malignancy was rendered based on cytologic findings (two metastatic squamous-cell carcinomas and one melanoma). However, initial follow-up surgical pathology reported only "extensive coagulative necrosis, no viable tumor seen." Subsequent immunohistochemical stains (cytokeratins (AE1/AE3), HMB45, S100, and Melan A) demonstrated the presence of metastatic tumor in the area of infarction in each case, thus establishing the presence of metastatic tumor and correct interpretation of the initial FNA. We conclude, based on our own experience and a few previously reported cases, that total infarction of the lymph nodes following FNA can occur, and immunohistochemistry can be helpful in clinical management.     

Expression of ICAM-1, VCAM-1 and ELAM-1 in angiofollicular lymph node hyperplasia (Castleman''s disease): evidence for dysplasia of follicular dendritic reticulum cells

The inducible adhesion molecules mediate important functions in the lymphoid tissues. We have investigated the expression of intercellular adhesion molecule 1 (ICAM-1), endothelial leucocyte adhesion molecule 1 (ELAM-1), vascular cell adhesion molecule 1 (VCAM-1), and platelet endothelial cell adhesion molecule (PECAM/CD31), using immunocytochemistry on cryostat sections of five lymph nodes from patients with Castleman's disease of the hyaline-vascular type. All five cases were characterized by marked hyperplasia of follicular dendritic reticulum cells, which were extensively present even in the mantle zone. Hyperplastic follicular dendritic reticulum cells showed marked expression of VCAM-1, and weak expression of ICAM-1. In two cases, several dysplastic giant cells with aberrant, polyploid nuclei showed aberrant expression of ELAM-1, an endothelium-restricted molecule. Dysplastic giant cells were positive with DRC-1 (an antibody to dendritic reticulum cells), VCAM-1 and occasionally ICAM-1, were negative for the endothelial cell markers factor VIII-related antigen and CD31 and were non-proliferating (Kl-67-). Cells positive for ICAM-1 or VCAM-1 were rare in the interfollicular areas. In all cases vascular hyperplasia was prominent, but endothelial cells were poorly activated in terms of expression of inducible adhesion molecules and of HLA-DR antigens. The possibility that dysplastic follicular dendritic reticulum cells have a pathogenetic role in Castleman's disease is discussed.     

Immunohistochemical and enzyme-histochemical study on the accessory olfactory bulb of the dog

The accessory olfactory bulb (AOB) is a primary center of the vomeronasal system. In the dog, the position and morphology of the AOB remained vague for a long time. Recently, the morphological characteristics of the dog AOB were demonstrated by means of lectin-histochemical, histological, and immunohistochemical staining, although the distribution of each kind of neuron, especially granule cells, remains controversial in the dog AOB. In the present study, we examined the distribution of neuronal elements in the dog AOB by means of immunohistochemical and enzyme-histochemical staining. Horizontal paraffin or frozen sections of the dog AOB were immunostained with antisera against protein gene product 9.5 (PGP 9.5), brain nitric oxide synthase (NOS), glutamic acid decarboxylase (GAD), tyrosine hydroxylase (TH), substance P (SP), and vasoactive intestinal polypeptide (VIP) by avidin-biotin peroxidase complex method. In addition, frozen sections were stained enzyme-histochemically for NADPH-diaphorase. In the dog AOB, vomeronasal nerve fibers, glomeruli, and mitral/ tufted cells were PGP 9.5-immunopositive. Mitral/ tufted cells were observed in the glomerular layer (GL) and the neuronal cell layer (NCL). In the NCL, a small number of NOS-, GAD-, and SP-immunopositive and NADPH-diaphorase positive granule cells were observed. In the GL, GAD-, TH-, and VIP-immunopositive periglomerular cells were observed. In the GL and the NCL, TH-, and VIP-immunopositive short axon cells were also observed. In addition to these neurons, TH- and SP-immunopositive afferent fibers were observed in the GL and the NCL. We could distinctly demonstrate the distribution of neuronal elements in the dog AOB. Since only a small number of granule cells were present in the dog AOB, the dog AOB did not display such a well-developed GCL as observed in the other mammals. Anat. Rec. 252:393–402, 1998. © 1998 Wiley-Liss, Inc.     

Interdigitating cell sarcoma: A morphologic and immunologic study of lymph node lesions in four cases

lnterdigitating cell sarcoma is an extremely rare tumor. Its presentation and histologic appearance has varied among the reported cases. In this study, the authors investigated four cases of the hematolymphoid malignancy arising within lymph nodes, which were considered to be of interdigitating cell origin. All patients presented in the 6th to 8th decade of life with peripheral lymphadenopathy, and had a relatively indolent clinical course, without bone marrow or skin involvement. Carcinomas were observed as a second neoplasm in two of four patients. Distinctive morphologic features are proliferation of histiocyte-like cells with nuclear pleomorphism and occasionally multinucleated, paracortical distribution sparing of B-cell regions, fibrosis, sinus infiltration, and a prominent eosinophi/plasma cell infiltrates. The combination of light microscopic, fine structural, and immu-nohistochemical features suggested that these tumors derive from interdigitating cells: these tumor cells expressed CD68 (KP1), S-100 protein and HLA-DR, but lack CD21 (1F8), desmosomes and Birbeck granules. The diagnosis of interdigitating cell sarcoma should be considered on any pleo-morphic tumor with the features described in this report.     

Angiomyoid proliferative lesion: an unusual stroma-rich variant of Castleman's disease of hyaline-vascular type

The stroma-rich variant of Castleman's disease of hyaline-vascular type (CDHV) is a newly identified entity that shows overgrowth of a variety of stromal cells. Six CDHV patients showed proliferation of vasculature and actin-positive myoid cells in the expanded interfollicular (IF) area. There were three women and three men, and the median age was 29.5 years. Of the six lesions, four were located in the retroperitoneum, one in the neck, and one in the mediastinum. All patients were asymptomatic. Microscopically, the degree of widening of the IF area varied from slight overgrowth of the IF area (approximately 55% of the lymph node area) to vague nodularity and finally to the formation of prominent nodules. In the nodular lesions, lymph follicles were compressed and attenuated. In the IF area, there were numerous vessels and proliferation of spindle cells that possessed blunt nuclei. The long, slender, dendritic cytoplasms of the spindle cells were stained by alpha smooth muscle actin. The spindle cells were negative for desmin, CD34, factor VIII-related antigen, S-100, CD21, and CD68. No patient has had recurrence after simple excision. We maintain that these angiomyoid proliferative lesions in CDHV are of a hyperplastic nature. This condition encompasses proliferation of small vessels and myoid cells. Its characteristics include an asymptomatic, solitary nodule that predominantly develops in the retroperitoneum.     

Granulocytic sarcoma presenting with lymph node infarction at disease onset

A completely infarcted lymph node is an unusual event. However, lymph node infarction should alert the pathologist to the considerable likelihood of malignant lymphoma. We report two unusual cases of acute myeloid leukemia presenting with granulocytic sarcoma at disease onset with a lymph node lesion exhibiting extensive lymph node infarction. The infarcted tissue contained numerous eosinophilic cell ghosts. There were some islands of degenerated, pyknotic medium-sized nuclei resembling lymphoblasts present in the necrotic area. By immunohistochemistry, these medium sized cells were CD3-, CD20-, CD34+, CD43+, CD45RO-, CD68-, CD79a- and myeloperoxidase+ in both cases. Differentiation of granulocytic sarcoma from malignant lymphomas is important for adequate therapy. The present cases indicate that granulocytic sarcoma should be added to the list of differential diagnoses for lymph node infarction.     

Primary marginal zone B-cell lymphoma of the lymph node resembling plasmacytoma arising from a plasma cell variant of Castleman's disease. A clinicopathological and immunohistochemical study of seven patients

Nodal marginal zone B-cell lymphomas (NMZBL) occasionally represent prominent plasma cell differentiation. Recently, we presented a patient with NMZBL who exhibited histological features that resembled plasmacytoma arising from a localized plasma cell variant of Castleman's disease. To further clarify the clinicopathological, immunohistochemical, and genotypical findings, we studied seven such patients. Clinically, these patients were characterized by localized disease and an indolent clinical course with a slowly growing bulky mass in the affected lymph node. Only one patient exhibited paraproteinemia. Histologically, the lesions were characterized by numerous evenly distributed germinal centers in extensive sheets of plasma cells. Various numbers of centrocyte-like (CCL) cells arranged in a marginal zone distribution pattern occupied the peripheral region of the lymph node. The majority of the lymphoid follicles had atrophic or regressive germinal centers. A few lymphoid follicles were colonized by CCL cells. Immunohistochemistry showed that all of the lesions contained a monoclonal plasma cell population. In three tumors, a number of the CCL cells had a similar light chain restriction pattern to that observed in plasma cells. Two of the four patients evaluated exhibited clonal bands for the IgH gene by polymerase chain reaction assay. Moreover, the presence of surface IgM+, IgD- and CD27+ CCL- cells suggests that these tumors are derived from memory B-lymphocytes.     

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.     

Immunoglobulin and T-cell receptor gene rearrangement in Castleman's disease: molecular genetic analysis

AIMS: Castleman's disease (CD) is a rare heterogeneous disorder that is associated with an increased risk of developing lymphoma. Whether CD is primarily hyperplastic or neoplastic in origin is not yet clear. The aim of this study was to investigate CD further by determining the clonality status of its lymphocyte populations. METHODS AND RESULTS: We reviewed 20 patients with CD, 15 with the hyaline-vascular type and five with the plasma cell type. Immunoglobulin (JH) and T-cell receptor (TCR) gene rearrangements were examined using polymerase chain reaction and Southern blotting techniques. B-lymphocyte clonality was also assessed by flow cytometry (FC) and by immunohistochemistry (IHC). The age range of the patients was 15-66 years: nine female and 11 male. Monoclonal rearrangement of the immunoglobulin (JH) gene was detected in only one case. No cases were positive for monoclonal rearrangement of the TCR gene. All of the cases except one were negative for immunoglobulin light chain restriction by both FC and IHC. CONCLUSIONS: The lymphoid cells in CD are most commonly polyclonal in origin, which supports a non-neoplastic origin. However, rare cases may show lymphocyte monoclonality, which could represent the development of a neoplastic population. The latter cases should be followed closely.     

Castleman并发Hodgkin病1例报道及文献复习

目的：探讨以Ｃａｓｔｌｅｍａｎ病组织学特征为主要表现的Ｈｏｄｇｋｉｎ病的病理学特点及两者之间的关系。方法：对１例以Ｃａｓｔｌｅｍａｎ病组织学特征为主要表现的Ｈｏｄｇｋｉｎ病进行了光镜、免疫组织化学及原位分子杂交的观察。结果：淋巴结组织内淋巴滤泡明显增生,淋巴滤光性发中心大小正常或较小,部分滤泡中中心网状细胞增生,小淋巴包 套状排列似洋苞皮样结构,滤泡间及副皮质区见有明显增生的血管,部分血管壁增厚并     

Histopathological study of lymph node lesions in the acute phase of Kawasaki disease

Aims: To review the histopathological features of cervical LNs, and to clarify the changes in extracervical LNs, in acute Kawasaki disease (KD). Methods and results: The samples were obtained from 33 patients with acute‐phase KD. We divided the LNs into those in the neck (n = 23) and those located elsewhere (n = 26), and investigated them histologically. Changes occur not only in the cervical region, but also in LNs throughout the body. Most lymphadenopathy is non‐specific, caused by sinus expansion and paracortical zone enlargement, but there are also necrotic lesions of various sizes that can be surmised to result from ischaemic changes in some LNs. Necrotic foci start to develop immediately below the capsule, and are accompanied by fibrin thrombi in the small vessels and perivascular nuclear debris. Especially in the case of cervical LNs with necrosis, a high degree of non‐purulent inflammation develops in the LN capsule and surrounding connective tissue. Conclusions: In addition to lymphadenopathy with necrosis, KD should be suspected if there is non‐purulent inflammation of the LN capsule and/or surrounding connective tissue featuring mainly monocytes/macrophages.     

Kikuchi‐fujimoto disease in fine‐needle aspiration smears: A clinico‐cytologic study of 76 cases of KFD and 684 cases of reactive hyperplasia of the lymph node

Kikuchi‐Fujimoto disease (KFD) is cytologically characterized by a polymorphous lymphoid cell population, abundant karyorrhectic debris and histiocytes, many of which are crescentic (Kikuchi histiocytes). As per reviewed literature, KFD may be confused with tuberculosis, lymphoma, and reactive hyperplasia of lymph nodes (RHLN). Since RHLN was found to be a major challenging factor during routine cytodiagnosis of KFD in our material, we tried to find out the differentiating clinico‐cytologic features between 76 KFD and 684 RHLN cases seen in Kuwait. 63.2% of KFD were in 3rd and 4th decades of life as compared to 40.2% of RHLN (P = 0.0002). Male to female ratio was 1: 2.45 for KFD and 1:1.09 for RHLN (P = 0.0022). Kuwaiti:non‐Kuwaiti ratio was 1:2.04 for KFD and 1.31:1 for RHLN (P < 0.0001). Capillary networks was present in 71.1% of KFD smears and 52.6% of RHLN (P = 0.0023). Tingible body macrophages and dendritic reticulum cells were detected in 17.1% and 22.4%, respectively, in KFD as opposed to 50.1% and 58.8%, respectively, in RHLN (P < 0.0001). Kikuchi histiocyte count ranged from 2 to 36% in KFD and was ≥10% in 31 (40.8%). Rare Kikuchi histiocytes were detected in 16 (2.3%) of RHLN cases but in none of them the count exceeded 1%, whereas their count was >1% in all KFD cases (P < 0.0001). Thus, KFD cases differed significantly from RHLN in respect of age and sex distribution, Kuwaiti:non‐Kuwaiti ratio, and cytomorphologic features such as capillary networks, Kikuchi histiocyte count, dendritic reticulum cells, and tingible body macrophages. Diagn. Cytopathol. 2013;41:288–295. © 2011 Wiley Periodicals, Inc.