Brief Communication Acta Haematol 2014;132:73–74 DOI: 10.1159/000357109
Received: September 10, 2013 Accepted: October 28, 2013 Published online: January 30, 2014
Paraneoplastic Pemphigus Occurs Most Commonly in Indolent B Cell Lymphoma Keiko Morikawa a Takahiro Tsuji a Hiroshi Yamasaki a Sho Egashira b Atsushi Kaguchi b Masato Kido b Hiroyuki Tsuda a
Paraneoplastic pemphigus (PNP) was first described by Anhalt et al. in 1990 [1]. It is a rare autoimmune mucocutaneous disease characterized by severe stomatitis, polymorphous skin eruptions and underlying neoplasms, most commonly lymphoma. Firstly, we report a typical case of PNP with follicular lymphoma (FL). Then, we show the pathological characteristics of lymphoma associated with this disorder. A 65-year-old Japanese woman was referred to our hospital for evaluation of erosions on the conjunctiva and oral mucosa. She also had red papulae that had arisen on the back and extremities, and erythema palmare similar to erythema multiforme exudativum. Computed tomography revealed a para-aortic mass of around 8 cm in diameter. In the complete laboratory profiles of the serum, lactate dehydrogenase and soluble interleukin 2 receptor were elevated. Biopsy of the abdominal mass was performed and the diagnosis of FL was obtained. The clinical stage was IIIA. Biopsy specimens obtained from the inferior limb skin showed lichen planus-like features. Indirect immunofluorescence testing with a rat bladder section showed the presence of autoantibodies in the patient’s serum. Immunoblot analysis using normal human epidermal extracts detected IgG autoantibodies to the 190-kDa periplakin. Serum autoantibodies reacting with © 2014 S. Karger AG, Basel 0001–5792/14/1321–0073$39.50/0 E-Mail [email protected] www.karger.com/aha
desmoglein 3 were detected by enzyme-linked immunosorbent assay. From these results, the diagnosis of PNP was made. The patient was treated with an R-CHOP regimen (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone). Since severe infection developed, we changed the treatment to rituximab monotherapy and then to R-CVP (rituximab, cyclophosphamide, vincristine and prednisolone). After treatment, the paraaortic mass had shrunk and the patient’s conjunctivitis, oral mucosal ulceration and truncal rash had improved. However, 5 months after the diagnosis of PNP, she developed dyspnea with an almost normal chest roentgenogram. A pulmonary function test revealed severe obstructive and restrictive airway disorder. It was proved that she had developed bronchiolitis obliterans, which is a common complication of PNP. Because there is no effective treatment for bronchiolitis obliterans at present [2], she was transferred to another hospital for palliative therapy. According to a recent study that examined 163 patients with PNP, the percentages of underlying disease were as follows: chronic lymphocytic leukemia (CLL; 18.4%), nonHodgkin’s lymphoma (NHL; 38.6%), Castleman’s disease (18.4%) and benign thymoma (5.5%) [3]. However, to the best of our knowledge, there have been no reports showing the detailed pathology of NHL. Therefore, in order to clarKeiko Morikawa Higashi-ku Koto 1-1-60 Kumamoto 862-8505 (Japan) E-Mail keiko_milfoil @ yahoo.co.jp
Downloaded by: Universitätsbibliothek Giessen 134.176.129.147 - 5/12/2015 4:26:48 PM
Departments of a Hematology and Oncology and b Dermatology, Kumamoto City Hospital, Kumamoto, Japan
Diffuse large B cell lymphoma
7% 7%
CLL 43%
FL Other indolent B cell lymphomas Other B cell lymphomas
27%
T cell lymphomas
Fig. 1. Associated lymphoma of the 56 patients with PNP.
ify this, we searched for references to lymphoma-associated PNP describing the lymphoma pathology. We searched Medline (‘PubMed’) using the keyword combinations ‘paraneoplastic pemphigus’ and ‘lymphoma’ or ‘chronic lymphocytic leukemia’ for articles published since 2000, omitting cases in which the pathology or characteristics of lymphoma cells were not described. As a result, there were 56 cases of NHL-associated PNP. These consisted of 24 CLL cases (43%), 15 FL cases (27%), 3 diffuse large B cell lymphoma cases (5%) and 14 lymphomas with another pathology (25%), which included 4 indolent B cell lympho-
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Acta Haematol 2014;132:73–74 DOI: 10.1159/000357109
mas (7%), 4 B cell lymphomas with pathology unspecified and 6 T cell lymphomas (11%; fig. 1). Thus, it was revealed that 89% of the underlying lymphoma of PNP was with the B cell phenotype. It was particularly noteworthy that indolent B cell lymphomas such as CLL and FL accounted for 86% of B cell lymphomas and 77% of all lymphomas. This is the first report describing the detailed pathology of lymphoma associated with PNP. The pathophysiology of PNP is mostly unknown. Considering the characteristics of growth of indolent lymphomas, it is assumed that lymphoma is long present before the onset of pemphigus. Immunological perturbation by lymphoma might lie in the background of pemphigus.
References 1 Anhalt GJ, Kim SC, Stanley JR, Korman NJ, Jabs DA, Kory M, Izumi H, Ratrie H 3rd, Mutasim D, Ariss-Abdo L, Labib RS: Paraneoplastic pemphigus: an autoimmune mucocutaneous disease associated with neoplasia. N Engl J Med 1990;323:1729–1735. 2 Saito S, Sanui M, Fujii T, Endo A, Saito K, Iwai K, Uchino S, Takinawi M: Bronchiolitis obliterans presenting as prolonged ventilator dependence in a patient with paraneoplastic pemphigus. Anaesth Intensive Care 2012;40:726–728. 3 Kaplan I, Hodak E, Ackerman L, Mimouni D, Anhalt GJ, Calderon S: Neoplasms associated with paraneoplastic pemphigus: a review with emphasis on non-hematologic malignancy and oral mucosal manifestations. Oral Oncol 2004;144:1102–1104.
Morikawa /Tsuji /Yamasaki /Egashira / Kaguchi /Kido /Tsuda
Downloaded by: Universitätsbibliothek Giessen 134.176.129.147 - 5/12/2015 4:26:48 PM
11%
5%
Received: September 10, 2013 Accepted: October 28, 2013 Published online: January 30, 2014
Paraneoplastic Pemphigus Occurs Most Commonly in Indolent B Cell Lymphoma Keiko Morikawa a Takahiro Tsuji a Hiroshi Yamasaki a Sho Egashira b Atsushi Kaguchi b Masato Kido b Hiroyuki Tsuda a
Paraneoplastic pemphigus (PNP) was first described by Anhalt et al. in 1990 [1]. It is a rare autoimmune mucocutaneous disease characterized by severe stomatitis, polymorphous skin eruptions and underlying neoplasms, most commonly lymphoma. Firstly, we report a typical case of PNP with follicular lymphoma (FL). Then, we show the pathological characteristics of lymphoma associated with this disorder. A 65-year-old Japanese woman was referred to our hospital for evaluation of erosions on the conjunctiva and oral mucosa. She also had red papulae that had arisen on the back and extremities, and erythema palmare similar to erythema multiforme exudativum. Computed tomography revealed a para-aortic mass of around 8 cm in diameter. In the complete laboratory profiles of the serum, lactate dehydrogenase and soluble interleukin 2 receptor were elevated. Biopsy of the abdominal mass was performed and the diagnosis of FL was obtained. The clinical stage was IIIA. Biopsy specimens obtained from the inferior limb skin showed lichen planus-like features. Indirect immunofluorescence testing with a rat bladder section showed the presence of autoantibodies in the patient’s serum. Immunoblot analysis using normal human epidermal extracts detected IgG autoantibodies to the 190-kDa periplakin. Serum autoantibodies reacting with © 2014 S. Karger AG, Basel 0001–5792/14/1321–0073$39.50/0 E-Mail [email protected] www.karger.com/aha
desmoglein 3 were detected by enzyme-linked immunosorbent assay. From these results, the diagnosis of PNP was made. The patient was treated with an R-CHOP regimen (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone). Since severe infection developed, we changed the treatment to rituximab monotherapy and then to R-CVP (rituximab, cyclophosphamide, vincristine and prednisolone). After treatment, the paraaortic mass had shrunk and the patient’s conjunctivitis, oral mucosal ulceration and truncal rash had improved. However, 5 months after the diagnosis of PNP, she developed dyspnea with an almost normal chest roentgenogram. A pulmonary function test revealed severe obstructive and restrictive airway disorder. It was proved that she had developed bronchiolitis obliterans, which is a common complication of PNP. Because there is no effective treatment for bronchiolitis obliterans at present [2], she was transferred to another hospital for palliative therapy. According to a recent study that examined 163 patients with PNP, the percentages of underlying disease were as follows: chronic lymphocytic leukemia (CLL; 18.4%), nonHodgkin’s lymphoma (NHL; 38.6%), Castleman’s disease (18.4%) and benign thymoma (5.5%) [3]. However, to the best of our knowledge, there have been no reports showing the detailed pathology of NHL. Therefore, in order to clarKeiko Morikawa Higashi-ku Koto 1-1-60 Kumamoto 862-8505 (Japan) E-Mail keiko_milfoil @ yahoo.co.jp
Downloaded by: Universitätsbibliothek Giessen 134.176.129.147 - 5/12/2015 4:26:48 PM
Departments of a Hematology and Oncology and b Dermatology, Kumamoto City Hospital, Kumamoto, Japan
Diffuse large B cell lymphoma
7% 7%
CLL 43%
FL Other indolent B cell lymphomas Other B cell lymphomas
27%
T cell lymphomas
Fig. 1. Associated lymphoma of the 56 patients with PNP.
ify this, we searched for references to lymphoma-associated PNP describing the lymphoma pathology. We searched Medline (‘PubMed’) using the keyword combinations ‘paraneoplastic pemphigus’ and ‘lymphoma’ or ‘chronic lymphocytic leukemia’ for articles published since 2000, omitting cases in which the pathology or characteristics of lymphoma cells were not described. As a result, there were 56 cases of NHL-associated PNP. These consisted of 24 CLL cases (43%), 15 FL cases (27%), 3 diffuse large B cell lymphoma cases (5%) and 14 lymphomas with another pathology (25%), which included 4 indolent B cell lympho-
74
Acta Haematol 2014;132:73–74 DOI: 10.1159/000357109
mas (7%), 4 B cell lymphomas with pathology unspecified and 6 T cell lymphomas (11%; fig. 1). Thus, it was revealed that 89% of the underlying lymphoma of PNP was with the B cell phenotype. It was particularly noteworthy that indolent B cell lymphomas such as CLL and FL accounted for 86% of B cell lymphomas and 77% of all lymphomas. This is the first report describing the detailed pathology of lymphoma associated with PNP. The pathophysiology of PNP is mostly unknown. Considering the characteristics of growth of indolent lymphomas, it is assumed that lymphoma is long present before the onset of pemphigus. Immunological perturbation by lymphoma might lie in the background of pemphigus.
References 1 Anhalt GJ, Kim SC, Stanley JR, Korman NJ, Jabs DA, Kory M, Izumi H, Ratrie H 3rd, Mutasim D, Ariss-Abdo L, Labib RS: Paraneoplastic pemphigus: an autoimmune mucocutaneous disease associated with neoplasia. N Engl J Med 1990;323:1729–1735. 2 Saito S, Sanui M, Fujii T, Endo A, Saito K, Iwai K, Uchino S, Takinawi M: Bronchiolitis obliterans presenting as prolonged ventilator dependence in a patient with paraneoplastic pemphigus. Anaesth Intensive Care 2012;40:726–728. 3 Kaplan I, Hodak E, Ackerman L, Mimouni D, Anhalt GJ, Calderon S: Neoplasms associated with paraneoplastic pemphigus: a review with emphasis on non-hematologic malignancy and oral mucosal manifestations. Oral Oncol 2004;144:1102–1104.
Morikawa /Tsuji /Yamasaki /Egashira / Kaguchi /Kido /Tsuda
Downloaded by: Universitätsbibliothek Giessen 134.176.129.147 - 5/12/2015 4:26:48 PM
11%
5%
