case report paraneoplastic pemphigus associated with...

Case ReportParaneoplastic Pemphigus Associated with Follicular DendriticCell Tumor in the Mediastinum

Aparna Mullangath Prakasan,1 Anne Jennifer Prabhu,2 Kanmani Velarasan,1

Selvamani Backianathan,1 and Thomas Samuel Ram1

1 Ida B Scudder Cancer Centre, Radiation Oncology Unit 1, Christian Medical College, Ida Scudder Road, Vellore,Tamil Nadu 632004, India2Department of Pathology, Christian Medical College, Ida Scudder Road, Vellore, Tamil Nadu 632004, India

Correspondence should be addressed toThomas Samuel Ram; [email protected]

Received 22 November 2015; Revised 20 March 2016; Accepted 28 March 2016

Academic Editor: Soner Uzun

Copyright © 2016 Aparna Mullangath Prakasan et al. This is an open access article distributed under the Creative CommonsAttribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work isproperly cited.

Paraneoplastic Pemphigus (PNP) is an autoimmune bullous disease characterized by severe stomatitis, polymorphous skineruptions, and underlying neoplasms. Diagnosis of cutaneous paraneoplastic disorders requires high index of suspicion. Wedescribe a patient with PNP associated with follicular dendritic cell (FDC) tumor in the mediastinum, a rare neoplasm originatingfrom follicular dendritic cells. Its management requires identification of underlying malignancy and treatment of the same. Ourpatient showed remission of PNP upon excision of the tumor and remained disease-free for 8 years.

1. Introduction

Follicular dendritic cell tumors are rare neoplasms (0.4%of soft tissue sarcomas) [1], also called follicular dendriticreticulum cell tumor or follicular dendritic cell sarcoma.The behavior of these tumors is more like that of a low-grade soft tissue sarcoma than a malignant lymphoma andis characterized by local recurrences in 36% and distantmetastases in 28% of cases to liver or lung [2]. They areoften misdiagnosed. Immunohistochemical markers CD21and CD35 positivity is necessary for diagnosis [3]. Completesurgical resection is the primary modality of treatment. Therole of adjuvant treatment is not clearly defined. Patientswith risk features like high grade, large tumor size (>5 cm),recurrent tumor, and incomplete resection will benefit fromadjuvant treatment.

So far only 4 cases of FDC arising from Castleman’sdisease with Paraneoplastic Pemphigus (PNP) have beenreported in literature [4–7].

2. Case Report

A 39-year-old gentleman presented with persistent oral ero-sions and skin vesicles over the left forearm for 4 months

in June 2007. There was associated voice change, foreignbody sensation in eyes, and weight loss. Clinical examinationrevealed multiple erosions over lips, hard palate, and buccalmucosa with hemorrhagic crusts over the lips. There was asingle resolving vesicle over left forearm. Nikolsky and bullasign were negative. There was no palpable lymphadenopathy.The rest of the systemic examination was unremarkable.

Perilesional lip biopsy under Direct Immunofluorescence(IF) showed fishnet pattern fluorescence for IgG in the lowerthird of epidermis and coarse granular contiguous positivityfor C3 in the basal layer of keratinocytes. It was negativefor IgA and IgM. He was started on Prednisolone andAzathioprine for one month, but his lesions did not improve.

Routine chest X-ray done showed right sided hilar mass(Figure 1). Further evaluation with CT thorax revealed 6 ×3.8 cm, densely enhancing mass in the anterior and middlemediastinum (Figure 2).

He had thoracotomy and debulking of the mass of 6 ×5 cm tumor in the right lobe of thymus, adherent to rightphrenic nerve. There were no enlarged lymph nodes. Grossspecimen showed an ill-defined tumor of size 2.5 × 3.5 ×3 cm with homogenous yellowish tan surface. Microscopyshowed circumscribed spindle cell tumor composed of

Hindawi Publishing CorporationCase Reports in Dermatological MedicineVolume 2016, Article ID 6901539, 4 pageshttp://dx.doi.org/10.1155/2016/6901539

2 Case Reports in Dermatological Medicine

Figure 1: Chest X-ray showing right sided hilar mass.

Figure 2: CT thorax showing densely enhancing anterior andmiddle mediastinal mass.

interlacing fascicles with storiform pattern in a backgroundof lymphocytes (Figure 3). Immunohistochemistry revealedcells positive for CD21 and CD35 leading to a pathologicaldiagnosis of follicular dendritic cell tumor.

Patient had 2 major criteria of PNP (a) polymorphicmucocutaneous eruption and (b) concurrent internal neopla-sia and 2 minor criteria (a) Direct IF showing intercellularand basementmembrane staining and (b) Indirect IF stainingwith rat bladder epithelium with intracellular IgG stainingpositive and diagnosed to have FDC tumor of the anteriormediastinum with Paraneoplastic Pemphigus.

He received postoperative radiation therapy to the resid-ual mass in the anterior mediastinum (Figure 4). He wastreated with conventional anteroposterior-posteroanterior(AP-PA) technique, using 6MV X-rays, 45Gy in 25 fractionsto midplane, and 5 fractions per week over 5 weeks. The skinand oral lesions subsided at the end of treatment. At 8-yearfollow-up, he is free of disease (Figure 5).

(a)

(b)

Figure 3:Circumscribed spindle cell tumor composed of interlacingfascicles with storiform pattern and sprinkling of lymphocytes onmicroscopy.

3. Discussion

Follicular dendritic reticulum cells are found in B cell zones,particularly in germinal centers. They are nonlymphoid,nonphagocytic cells, and main function of this cell is tocapture and present antigens and immune complexes. Mostcommonly affected sites are lymph nodes and extranodalsites including liver, oral cavity, bowel, and spleen [8].Intra-abdominal location, size >5 cm, 6 or more mitoticfigures/10HPF, atypia, and coagulative necrosis are associatedwith poor prognosis [9]. Differential diagnosis includesother histiocytic and dendritic cell neoplasms, fibroblasticreticulum cell sarcoma (expresses desmin, SMA, and cytok-eratins), inflammatory pseudotumor (expression of FDCcell markers is weak), myofibroblastic tumors (positive formuscle specific actin), lymphoepithelioma-like carcinoma,malignant melanoma, thymoma, meningioma, malignantfibrous histiocytoma, and gastrointestinal stromal tumor.

WHO classifies dendritic neoplasm into Langerhans’cell histiocytosis, Langerhans cell sarcoma, interdigitatingdendritic cell sarcoma, follicular dendritic cell sarcoma, anddendritic cell sarcoma, not otherwise specified.

According to Fonseca et al. [10] surgery is the primarymodality of treatment for FDC. Benefit of consolidativeradiotherapy in preventing local recurrence in patients withlocalized disease either completely or incompletely resected

Case Reports in Dermatological Medicine 3

Figure 4: Postoperative chest X-ray showing residual mass in theanterior mediastinum.

Figure 5: No residual lesion on chest X-ray on follow-up.

has been documented. Being so similar to lymphomas, physi-cians began using a common leukemia and non-Hodgkin’slymphoma chemotherapy regimen like CHOP and it hadshown nondurable antitumor activity in FDC [10, 11].

Criteria for diagnosis of PNP include three major cri-teria or two major and two minor criteria. Major signs ofParaneoplastic Pemphigus include (1) polymorphic muco-cutaneous eruption, (2) concurrent internal neoplasia, and(3) serum antibodies with a specific immunoprecipitationpattern. Minor signs of Paraneoplastic Pemphigus include(1) histologic evidence of acantholysis, (2) Direct IF showingintercellular and basement membrane staining, and (3) Indi-rect IF staining with rat bladder epithelium. Most constantlaboratory finding is the characteristic immunoprecipitationpattern.

A review of 163 case reports of PNP by Kaplan et al.[12] reported that 84% of cases were associated with hema-tologic malignancies like non-Hodgkin’s lymphoma [39%],

Chronic Lymphocytic Leukemia [18%], Castleman’s disease[18%], thymoma [6%], Waldenstrom macroglobulinemia[1%], Hodgkin’s lymphoma [1%], andmonoclonal gammopa-thy [1%]. The remaining 16% were associated with nonhema-tologic neoplasms such as epithelial origin carcinoma [9%],mesenchymal origin sarcoma [6%], andmelanoma [1%].Oralulcerations were the presenting feature in 45% of all cases andappear to be a key feature of PNP.

Treatment of PNP includes identification of the underly-ing neoplasm and its treatment. In Leger and Picard reviewarticle, the overall survival for series of patients with PNP for1 year, 3 years, and 5 years was found to be 49%, 41%, and 38%,respectively [13].

Differential diagnosis of anterior mediastinal mass withPNP includes lymphoproliferative disorders like thymiccarcinoid, Castleman’s disease, and nonlymphoproliferativedisorders like sarcoma and lung carcinoma. Diagnosis ofcutaneous paraneoplastic disorders requires high index ofsuspicion.

Our patient presented with PNP, an autoimmune bullousdisease characterized by severe stomatitis and polymorphousskin eruptions occurring in association with various formsof underlying neoplasia. It is characterized by the presenceof autoantibodies that react with intermediate filament-associated proteins in desmosomes and hemidesmosomes,desmoplakin, bullous pemphigoid antigen 1, and envoplakin.

In case reports with similar presentation (FDC withPNP), first patient’s condition improved after excision oftumor [4] and second patient showed no improvement,possibly because of the occurrence of severe pulmonaryinvolvement [5], third patient expiredwith septicemia follow-ing excision of the tumor [6], and fourth patient expired after1st course of R-CHOP chemotherapy due to pseudomonasinfection [7]. Our patient is found to be disease-free at 8-yearfollow-up.

Diagnosis of cutaneous paraneoplastic disorders requireshigh index of suspicion. Incorrect treatment can lead toadverse toxic effects of drugs. Its management requires iden-tification of underlying malignancy and a multidisciplinarytreatment of the same.

Competing Interests

The authors declare that they have no competing interests.

References

[1] M. Sharpe, S. E. Easthope, G. M. Keating, and H. M. Lamb,“Polyethylene glycol-liposomal doxorubicin: a review of its usein the management of solid and haematological malignanciesand AIDS-related Kaposi’s sarcoma,” Drugs, vol. 62, no. 14, pp.2089–2126, 2002.

[2] B. Perez-Ordonez and J. Rosai, “Follicular dendritic cell tumor:review of the entity,” Seminars in Diagnostic Pathology, vol. 15,no. 2, pp. 144–154, 1998.

[3] D. A. Biddle, J. Y. Ro, G. S. Yoon, Y.-W.H. Yong, A. G. Ayala, andN. G. Ordonez, “Extranodal follicular dendritic cell sarcoma ofthe head and neck region: three new cases, with a review of theliterature,”Modern Pathology, vol. 15, no. 1, pp. 50–58, 2002.

4 Case Reports in Dermatological Medicine

[4] I.-J. Lee, S.-C. Kim, H. S. Kim et al., “Paraneoplastic pemphigusassociated with follicular dendritic cell sarcoma arising fromCastleman’s tumor,” Journal of the American Academy of Der-matology, vol. 40, no. 2, pp. 294–297, 1999.

[5] A. V. Marzano, P. Vezzoli, F. Mariotti, V. Boneschi, R. Caputo,and E. Berti, “Paraneoplastic pemphigus associated with fol-licular dendritic cell sarcoma and Castleman disease,” BritishJournal of Dermatology, vol. 153, no. 1, pp. 214–215, 2005.

[6] H. Yamada, Y. Nobeyama, K. Matsuo et al., “A case of paraneo-plastic pemphigus associatedwith triplemalignancies in combi-nation with antilaminin-332 mucous membrane pemphigoid,”British Journal of Dermatology, vol. 166, no. 1, pp. 230–231, 2012.

[7] S. Baghmar, S. Kumar, S. D. Gupta, and V. Raina, “Folliculardendritic cell sarcoma with paraneoplatic pemphigus: rare caseand a brief review of literature,” Indian Journal of Medical andPaediatric Oncology, vol. 34, no. 4, pp. 317–319, 2013.

[8] J. K. Chan, W. Y. Tsang, C. S. Ng, S. K. Tang, H. C. Yu, and A.W. Lee, “Follicular dendritic cell tumors of the oral cavity,”TheAmerican Journal of Surgical Pathology, vol. 18, no. 2, pp. 148–157, 1994.

[9] J. K. C. Chan, C. D. M. Fletcher, S. J. Nayler, and K. Cooper,“Follicular dendritic cell sarcoma: clinicopathologic analysis of17 cases suggesting a malignant potential higher than currentlyrecognized,” Cancer, vol. 79, no. 2, pp. 294–313, 1997.

[10] R. Fonseca, M. Yamakawa, S. Nakamura et al., “Follicular den-dritic cell sarcoma and interdigitating reticulum cell sarcoma: areview,” American Journal of Hematology, vol. 59, no. 2, pp. 161–167, 1998.

[11] J. K. Chan, C. D. Fletcher, S. J. Nayler, and K. Cooper, “Folliculardendritic cell sarcoma. Clinicopathologic analysis of 17 casessuggesting a malignant potential higher than currently recog-nized,” Cancer, vol. 79, no. 2, pp. 294–313, 1997.

[12] I. Kaplan, E. Hodak, L. Ackerman, D. Mimouni, G. J. Anhalt,and S. Calderon, “Neoplasms associated with paraneoplasticpemphigus: a reviewwith emphasis on non-hematologicmalig-nancy and oral mucosal manifestations,”Oral Oncology, vol. 40,no. 6, pp. 553–562, 2004.

[13] S. Leger and D. Picard, “Prognostic factors of paraneoplasticpemphigus,” Archives of Dermatology, vol. 148, no. 10, pp. 1165–1172, 2012.

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