Paraneoplastic pemphigus associated with Castleman tumor: a commonly reported subtype of paraneoplastic pemphigus in China

BACKGROUND: Castleman tumor, a rare lymphoproliferative disorder, is one of the associated tumors in paraneoplastic pemphigus. We analyzed the characteristics of a group of patients with Castleman tumor to clearly understand and to improve the prognosis of the disease. OBSERVATIONS: Ten cases of paraneoplastic pemphigus associated with Castleman tumor treated in the Department of Dermatology, Peking University First Hospital, Beijing, China, from May 1, 1999, to March 31, 2004, were analyzed for clinical aspects, characteristics and histologic features of the tumors, and computed tomographic findings. Literature was reviewed and data were compared with our cases. Castleman tumor was a frequently reported neoplasm in association with paraneoplastic pemphigus in China. The disease was found to be caused by an autoimmune reaction originating from the B lymphocytes in the Castleman tumor. CONCLUSIONS: Castleman tumor in association with paraneoplastic pemphigus is a commonly reported subtype of paraneoplastic pemphigus in China. Early detection and removal of the Castleman tumor are crucial for the treatment of this tumor-associated autoimmune disease.     

Cutaneous and systemic plasmacytosis in an Asian male born in the North American continent: A controversial entity potentially related to multicentric Castleman disease

Cutaneous and systemic plasmacytosis is a rare condition primarily affecting middle‐aged individuals of Japanese descent and has principally been reported in cases originating from Asia. Its relationship, if any, to Castleman disease, is controversial. The authors report a case of cutaneous and systemic plasmacytosis involving a 36‐year‐old man of Chinese ancestry born in North America. The biopsy of an involved lymph node revealed changes resembling Castleman disease. Significantly, this case to our knowledge represents the first case of cutaneous and systemic plasmacytosis presenting in a patient of Chinese ancestry born on the North American mainland. Shadel BN, Frater JL, Gapp JDG, Hurley MY. Cutaneous and systemic plasmacytosis in an Asian male born in the North American continent: A controversial entity potentially related to multicentric Castleman disease.     

Multicentric plasma cell variant of Castleman's disease with cutaneous involvement

BACKGROUND: Castleman's disease (CD) is a rare low-grade B-cell lymphoproliferative disorder that can be associated with a variety of antibody-mediated paraneoplastic syndromes. The disease is classified clinically by two forms and three histologic variants. METHODS: We describe the clinical and pathological features of a 44-year-old woman who presented with an autoimmune hemolytic anemia, thrombocytosis, polyclonal gammopathy, axillary lymphadenopathy, hepatosplenomegaly, and several erythematous and violaceous nodules and plaques without scaling involving the trunk and extremities. RESULTS: Histologic examination of the skin lesions revealed a deep dermal and subcutaneous nodular mononuclear infiltrate composed primarily of polyclonal plasmacytoid cells without atypia and an increased vascular proliferation. Additional studies including a bone marrow and lymph node biopsy, serum and urine protein electrophoresis, and computed tomography scans supported the diagnosis of multicentric plasma cell variant of CD with an associated autoimmune paraneoplastic hemolytic anemia. CONCLUSION: Cutaneous involvement in CD is part of the multicentric nature and should be considered in the differential diagnosis of a polyclonal plasma cell-rich lymphoproliferative disorder associated with paraneoplastic autoimmune disease.     

Autoantibody production from a thymoma and a follicular dendritic cell sarcoma associated with paraneoplastic pemphigus

BACKGROUND: Paraneoplastic pemphigus (PNP) is an autoimmune mucocutaneous disease. We previously reported that B cells in a Castleman tumour associated with PNP produced autoantibodies. However, it is uncertain whether the production of autoantibodies from the associated tumour is a common mechanism in PNP. OBJECTIVES: To investigate autoantibody production in a thymoma and a follicular dendritic cell sarcoma that were excised from two patients with PNP. METHODS: Tumour cells were cultured, and their surface markers were identified. Indirect immunofluorescence, immunoblotting and enzyme-linked immunosorbent assay (ELISA) using culture media from the tumours were used to detect PNP autoantibodies. RESULTS: B cells with markers (CD22+, surface membrane IgG+ and surface membrane IgM+) of mature B lymphocytes constituted a proportion of cultured tumour cells in both tumours. Western blot showed that the medium from both the thymoma and the follicular dendritic cell sarcoma cells recognized 190-kDa periplakin and 210-kDa envoplakin bands of human epithelial proteins as well as recombinant linker regions of periplakin, envoplakin, desmoplakin and bullous pemphigoid antigen 1. ELISA was positive for antidesmoglein 3 antibody. CONCLUSIONS: The presence and localization in tumours of B-lymphocyte clones against proteins of the plakin family and desmoglein 3 in skin may not be confined to PNP with Castleman disease, but is possibly a common mechanism in PNP associated with various tumours.     

Unusual case of multicentric mixed-type Castleman's disease presenting with exfoliative dermatitis

Castleman's disease is a rare disorder that results in the underregulated growth of lymphoid tissue. It may present as benign involvement of one lymph node group or as multicentric disease with systemic symptoms. We here present a patient with Castleman's disease of mixed-type and multicentric involvement.     

伴发副肿瘤性天疱疮的Castleman瘤——附10例报告

目的了解Castleman瘤伴发副肿瘤性天疱疮的临床特点。方法分析总结我科诊治的10 例Castleman瘤伴发副肿瘤性天疱疮的临床特点和治疗方法。结果 Castleman瘤为我国最常见伴发副肿瘤性天疱疮的肿瘤,其临床表现、皮损和肿瘤的病理学特点、CT及免疫学特点都较独特。肿瘤切除手术中给予静脉滴注丙种球蛋白,对降低术后呼吸道症状的出现,使患者早日康复是有益的。结论由于肿瘤直接产生抗体致病,因此早期诊断、早期切除肿瘤,是成功治疗本病的关键。     

CD56-Positive cutaneous lymphoma with multicentric Castleman's disease-like systemic manifestations.

We report a 55-year-old Japanese male with CD56+ cutaneous lymphoma. The patient had multiple cervical lymphadenopathy, a red nodule on his neck, and parotid gland nodularity. Histologic features of the biopsied cervical lymph node showed follicular hyperplasia with numerous plasma cells. A biopsied skin specimen of the nodule on his neck demonstrated dense infiltration of atypical large lymphocytes into the dermis. Immunohistochemical study of this specimen revealed CD3+, CD4+, and CD56+ expression in the majority of neoplastic cells. Polymerase chain reaction assays for the detection of Epstein-Barr virus sequences were positive for lymph node and skin DNA. Laboratory examinations showed polyclonal gammopathy, pancytopenia, and high serum interleukin-6 levels. These clinical and histological findings resembled those of multicentric Castleman's disease.     

Characterization of the dermal infiltrate in human immunodeficiency virus-infected patients with psoriasis

We investigated the dermal inflammatory cell infiltrates of psoriatic lesions from nine human immunodeficiency virus-infected patients and nine age-, sex-, and site-matched control specimens. The study was retrospective and observer blinded. T lymphocytes were quantitated using UCHL-1, a pan-T-cell monoclonal antibody, and plasma cell number was estimated in hematoxylin-eosin-stained sections. Differences in both variables reached statistical significance. There were fewer T cells and the number of plasma cells was significantly higher in specimens from the human immunodeficiency virus-positive individuals in comparison with control specimens. As plasma cells are readily identified on hematoxylin-eosin-stained sections, their presence in skin biopsy specimens from psoriatic leisons should arouse suspicion of human immunodeficiency virus infection. The depletion of helper/inducer T lymphocytes by the human immunodeficiency virus may promote the presence of plasma cells in cutaneous inflammatory infiltrates.     

Two HHV8-related illnesses in a HIV-negative patient: Kaposi's sarcoma and multicentric Castleman's disease. Response to treatment with Rituximab and CHOP

Human herpes virus 8 (HHV8) was discovered in 1994 in the biopsy of a Kaposi's sarcoma in a patient with AIDS. Since then it has been identified in all variants of Kaposi's sarcoma and in another two rare disorders: multicentric Castleman's disease and primary body-cavity based lymphomas. The case discusses a 68 year old, HIV-negative male patient, presenting Kaposi's sarcoma for one year and being monitored by dermatology, who presented for weakness, anorexia and fever. On examination, he was found to have adenitis of the lymph nodes in his neck, underarm and groin. A biopsy on one of the swellings led to findings characteristic of multicentric plasma cell variant Castleman's disease. Blood tests for HHV8 and HIV were carried out, resulting positive and negative respectively (IgG anti-HHV8 positive, title 1/640, indirect immunofluorescence). PCR amplification showed HHV8 in peripheral blood. Patient received 8 cycles of CHOP and rituximab, leading to complete disappearance of the adenitis and general symptoms, with no worsening of his Kaposi's sarcoma. Patient remained in complete remission for 10 months after treatment. This paper discusses the case of a HIV-, HHV8+ patient, diagnosed with classic Kaposi's sarcoma, who developed multicentric plasma cell variant Castleman's disease. The coincidence of two or more HHV8-related illnesses in a HIV-negative patient has rarely been described in medical literature. Treatment with rituximab combined with CHOP chemotherapy was effective in this case, and no worsening of the patient's KS was observed.     

7例副肿瘤性天疱疮临床分析

目的明确副肿瘤性天疱疮的I临床特点、治疗方法及预后。方法回顾分析我院2008年到2013年间收治的副肿瘤性天疱疮患者7例,分析其临床表现、伴随的肿瘤及组织病理学特点和实验室检查、治疗方法及预后。结果所有患者均有严重的黏膜损害,以口腔黏膜损害为突出表现,皮损以多形红斑、扁平苔藓样皮损和大疱最常见,最常见的特征性组织病理学为界面皮炎和凋亡的角质形成细胞。7例患者均为内脏单发肿瘤,其中以Castleman病最常见（n=6）,胸腺瘤（n=1）。其中3例死亡,1例手术后死于肺部感染,1例因自行停药而死亡,1例手术前死于败血症和严重复杂的多部位感染。手术后存活4例,最长已达5年以上,出现阻塞性细支气管炎仍未完全缓解;1例于手术后2年痊愈停药;另2例仍在1：7服泼尼松治疗。结论Castleman病是该组患者最常见的伴发肿瘤,及早发现并切除肿瘤是关键措施,手术前后的正确处理可提高其生存率。     

Secondary syphilis in persons infected with and not infected with HIV-1: a comparative immunohistologic study.

To better understand the cutaneous immune response to Treponema pallidum, we performed an immunohistologic study of skin biopsies from a total of 11 patients with secondary syphilis; biopsies from five persons infected with HIV-1 were included in the analysis to assess at the tissue level the impact of concomitant HIV-1 infection on disease expression. In all of the biopsies, staining for HLA-DR, a marker for cellular activation, was observed among infiltrating leukocytes, dermal vascular endothelial cells, and keratinocytes. Infiltrating mononuclear cells stained positively for CD4 or CD8, with CD4+ cells always being in the majority. Surprisingly, most of the CD4+ cells had histiocytic, rather than lymphocytic, morphologic characteristics. Immunostaining for CD14 confirmed that these cells were monocytic in origin, whereas immunostaining for CD3 revealed that the lymphocytes were predominantly CD8+ cytotoxic T cells. B cells were not detected despite the presence of variable numbers of plasma cells in all specimens. By immunofluorescence, all of the specimens demonstrated perivascular deposition of immunoglobulins, complement, or fibrinogen; linear staining at the dermal-epidermal junction also was observed in most of the specimens. No differences in immunocytochemical or immunofluorescence staining patterns were observed between the specimens from patients who were HIV positive and patients who were HIV negative. In addition to providing a more precise definition of the infiltrating cells in syphilitic lesions, our results, taken as a whole, indicate that cellular immune processes are largely responsible for the development of cutaneous manifestations during syphilitic infection and that coinfection with HIV-1 has little discernible effect on the cutaneous response to T. pallidum.     

Castleman tumor, lichen ruber and pemphigus vulgaris: paraneoplastic association of immunological diseases?

In a 45-year-old patient with an unusual clinical course of wide-spread cutaneous and oral lichen planus as well as pemphigus vulgaris of the oral cavity, both refractory to standard therapy, a Castleman tumour was suspected. Computer tomography disclosed a solid retroperitoneal tumour in the pelvis. After its surgical removal both dermatoses regressed substantially within a matter of weeks. In 1954 and again in 1956, Castleman described a thymoma-like lymph node hyperplasia, for which various synonyms are used. Castleman tumours are classified into the common hyalin-vascular type (80-90%), the rarer plasma cell type (10-20%) and the intermediate type. It is usually a benign lymphoma of variable location, but mostly intrathoracic. There is a remarkable association of Castleman tumours with skin diseases (lichen planus, pemphigus vulgaris, Kaposi sarcoma), neurological diseases (POEMS syndrome, myasthenia gravis, arteritis temporalis, Guillain-Barré syndrome), and internal diseases (nephrotic syndrome, amyloidosis, plasmacytoma, rheumatoid arthritis, thrombotic thrombocytopenic purpura). The coincidence of Castleman tumours with various immune phenomena and immunological diseases is higher than could be expected by chance, presenting a challenging pathophysiological model of antibodies and variable immunodeficiencies.     

Cutaneous and systemic plasmacytosis showing histopathologic features as mixed-type Castleman disease: a case report

Cutaneous and systemic plasmacytosis (CSP) is a rare disorder characterized by disseminated reddish brown plaques and polyclonal hypergammaglobulinemia. The lesions of CSP are histologically characterized by an infiltration of mature polyclonal plasma cells, which display similar pathological features to the plasma cell-type Castleman disease (CD). The relationship between CSP and CD is controversial. Herein, we described a 43-year-old man from China with disseminated reddish brown plaques and nodules on the cheek and temple. The serum level of immunoglobulin G and immunoglobulin A were higher than normal. In addition to mature plasma cell perivascular infiltrate in the dermis, the biopsy of the lesions showed small to medium-sized germinal follicles with hyalinized vessels and a concentrically arranged mantle zone. The patient had clinical features of CSP, but the biopsy revealed changes resembling mixed-type CD. To the best of our knowledge, this is the first case of CSP with the pathological features of mixed-type CD reported from China.     

A case of paraneoplastic pemphigus associated with Castleman’s disease presenting as erosive lichen planus

Paraneoplastic pemphigus (PNP) is a debilitating chronic blistering mucocutaneous disease associated with an underlying neoplasm and a poor prognosis. We present a patient who had been diagnosed and treated for recalcitrant erosive mucocutaneous lichen planus for 3 years with little success. Further investigations established the diagnosis of PNP with underlying Castleman’s disease. This case highlights the importance of repeated investigations to exclude PNP in patients with recalcitrant mucosal erosions, especially if atypical features are present.     

Castleman病继发副肿瘤性天疱疮和系统性红斑狼疮一例

【摘要】 患者男,47岁。反复口腔溃疡1年余,全身水疱9个月余。体检：口腔内见多处溃疡面,唇黏膜见片状糜烂面、黄色或黑褐色痂皮和嘴角浸渍发白,张口困难;鼻孔黏膜交界处、眼睑缘和阴茎冠状沟见黄褐色痂和脱痂后的淡红斑;躯干、四肢见散在红斑和水疱,大疱疱壁紧贴皮肤、部分破裂,基底潮红,类似多形红斑样改变,部分疱壁浑浊,见白色药痂黏着或黑色痂皮,尼氏征阴性;10指（趾）甲周见皱缩的水肿性暗红斑。水疱组织病理和皮损直接免疫荧光检查符合天疱疮诊断。纵隔肿瘤组织病理和免疫组化符合Castleman病（透明血管型）伴滤泡树突细胞增生。实验室检查：血清补体C3下降以及抗核抗体、抗核小体抗体、dsDNA抗体均阳性。诊断：Castleman病、副肿瘤性天疱疮、系统性红斑狼疮。用小剂量泼尼松和硫唑嘌呤治疗2个月后皮疹完全消退,免疫抑制药物缓慢减量,治疗6个月后,患者自行停用免疫抑制药物改为中药治疗,皮疹发展为中毒性表皮坏死松解症,最后死亡。该病在肿瘤切除后免疫抑制药物需维持一段较长时间,否则可导致皮疹反复或加重。     

Lyme disease is a spirochetosis. A review of the disease and evidence for its cause

Fourteen patients with Lyme disease showed typical clinical features of erythema chronicum migrans. Eighteen biopsy specimens in all were obtained from the cutaneous lesions of these patients. The predominant histologic finding was a superficial and deep perivascular and interstitial infiltrate composed mostly of lymphocytes, or lymphocytes and either plasma cells and eosinophils or both. The plasma cells were found most frequently in biopsy specimens taken from the peripheries of the lesions, whereas eosinophils were found mostly in the centers of lesions. With the Warthin-Starry silver stain, spirochetes were found mostly at the borders of the lesions an in biopsy specimens containing plasma cells. Spirochetes were subsequently cultured from a typical skin lesion of erythema chronicum migrans. These findings corroborate previous indirect evidence that a spirochete might be the cause of Lyme disease.     

Paraneoplastic pemphigus with fatal pulmonary involvement in a woman with a mesenteric Castleman tumour

A 42-year-old woman presented with oral and labial erosions, conjunctivitis, facial rash and lichenoid erythematous papules on the trunk. Paraneoplastic pemphigus (PNP) was suspected, and a search for a neoplasm revealed an intra-abdominal Castleman tumour sized 7 x 5 x 6 cm. After removal of the Castleman tumour, the skin and mucosal inflammation gradually subsided over the next 12 months. However, due to irreversible pulmonary involvement the patient died of intractable respiratory distress 2 years after the onset of the disease. Systemic corticosteroids, azathioprine, cyclophosphamide, high-dose intravenous immunoglobulins and thalidomide were ineffective. The diagnosis of PNP was confirmed by keratinocyte antigen immunoprecipitation with the patient's serum.     

Solitary reticulohistiocytic granuloma--a report of three cases and a review of literature

Case 1 was a 20-year-old male with a nodule on the scrotum. Case 2 was a 14-year-old female with a dome-shaped, reddish-brown nodule on the nose. Case 3 was a 30-year-old male with a dome-shaped, reddish-brown nodule on the forearm. All of the excised specimens showed typical features of solitary reticulohistiocytic granuloma. There were histiocytes and multi-nucleated giant cells in the dermal tumorous nests. They were stained positively with PAS reaction and anti-lysozyme antibody, but were stained negatively with S-100 protein antibody. To clarify the nosology of the reticulohistiocytic granuloma, we reviewed the literatures of multicentric reticulohistiocytosis and adult xanthogranuloma. Multicentric reticulohistiocytosis was considered to be a systemic disease and different from solitary reticulohistiocytic granuloma. However, adult xanthogranuloma showed clinical similarities to solitary reticulohistiocytic granuloma instead of the differences in the histopathologic features.     

Linear IgA disease in a patient with Castleman's disease

Linear IgA disease (LAD) is a well recognized subepidermal blistering disorder characterized by linear deposits of IgA at the basement membrane zone. The aetiology is unknown but there is a recognized association with lymphoproliferative malignancies. We report a case of LAD occurring in a patient with multicentric Castleman's disease (angiofollicular lymph node hyperplasia), an association not previously recorded in the literature.     

Disseminated neuroendocrine cancers of the skin--a cutaneous merkeliomatosis. Report of 2 cases

Two nearly identical cases with about 100 multicentric disseminated neuroendocrine carcinomas of the skin are presented. In the Merkel cell tumors a for epithelial cells specific antigen (MAM-6) was found by immunohistochemical methods. Only in one patient generalized metastases arose after a four year course of the disease. The other patient committed suicide after a three year course of the disease. At autopsy no metastases were seen. We assume these diseases to be a systemic proliferation of malignant neuroendocrine differentiated epithelial cells, for which the term "cutaneous Merkeliomatosis" is proposed.