UHOD Number: 1 Volume: 21 Year: 2011 57

Metastatic Thymoma with Good’s Syndrome Mimicking Bronchiectasis

Nurdan KOKTURK1, Asiye KANBAY1, Cuneyt KURUL2, Nalan AKYUREK3, Leyla MEMIS3, Sedat DEMIRCAN2, Haluk TURKTAS1

1 Gazi University Faculty of Medicine, Department of Pulmonary Medicine2 Gazi University Faculty of Medicine, Department of Thoracic Surgery

3 Gazi University Faculty of Medicine, Department of Pathology, Ankara, TURKEY

ABSTRACT

Thymomas are mysterious tumors commonly have unpredictable behaviors and may be associated with several paraneo-plastic conditions including Good’s syndrome. We reported a patient with a history of thymoma who presented with cen-trilobuler parenchymal lung nodules and recurrent sinopulmonary infections. The nodules were found to be thymoma metas-tasis which persisted in the lungs for 3 years. The diagnosis of Good’s syndrome was established in consistence with recur-rent infections and progressive hypogammaglobulinemia.

Keywords: Thymoma metastasis, Good’s syndrome, Amyloidosis

ÖZET

Bronflektaziyi Taklit Eden metastatik Timoma ve Good’s Sendromu

Timoma, Good’s Sendromu gibi humoral ve/veya hücresel immun yetmezli¤e neden olan paraneoplastiksendromlarla birlikte seyreden zor tan›nabilen tümördür. Good’s Sendromu hipogammaglobulinemi ve s›ktekrarlayan sinopulmoner enfeksiyonlar ile karakterizedir. Bu olgu sunusu, akci¤ere metastaz yapm›fl ve tedavi-siz kalm›fl olmas›na ra¤men en az 3 y›ll›k sa¤kal›m› tamamlam›fl olan ve s›k tekrarlayan enfeksiyonlar› hatal› birflekilde yaln›zca bronflektaziye ba¤lanm›fl bulunan timoma ve GS tan›s› konmufl bir hastay› tan›mlamaktad›r.

Anahtar Kelimeler: Timoma metastaz›, Good’s Sendromu, Amiloidoz

ULUSLARARASı HEMATOLOJI-ONKOLOJI DERGISI CASE REPORT International Journal of Hematology and Oncology

doi: 10.4999/uhod.08062

INTRODUCTIONThymomas are mysterious tumors that are present-ed with various paraneoplastic syndromes. Herein,a patient with thymoma, 40% have one or more pa-raneoplastic autoimmune condition, myastheniagravis being the most common. Other uncommonsyndromes are pure red cell aplasia, hypogammag-lobulinemia, limbic encephalitis, myocarditis,thyroiditis, etc. Herein, we present a patient with ahistory of thymoma who experienced recurrent si-nopulmonary infections and developed progressivehypogammaglobulinemia. He was found to havepulmonary metastases of thymoma and was eventu-ally diagnosed with Good’s Syndrome.

CASE REPORTA 47-year old male patient was admitted to our ins-titution in October 2003 with a history of frequentepisodes of coughing, sputum production, high fe-ver, sinusitis and dyspnea. He had experienced se-ven attacks of respiratory infections last year. Hehad been diagnosed with myasthenia gravis in1998. One year later of initial diagnosis, a medias-tinal mass consistent with thymoma had been dis-covered and thymectomy had been performed. Thehistological diagnosis had been predominantly cor-tical type of thymomas. The tumor had been stagedas Stage III according to the Masaoka classificati-on. He had received 50 Gy radiotherapy followingsurgery. He had experienced myasthenic crisis atthe end of the radiation therapy. Since then he hadbeen experiencing frequent exacerbations of upperand lower respiratory infections with high amountof sputum production. One year after thymectomy,thoracic computerized tomography (CT) showedoccasional ectatic bronchi and micronodules in lo-wer lobes of both lungs (Figure 1 a,b). The respira-tory infections were attributed to bronchiectasis. Atthat time, total immunoglobulin levels were foundto be normal except slightly lower level of IgA. Inthe present admission, a thoracic CT revealed mul-tiple centrilobuler parenchymal micronodules parti-cularly dominating at lower lobes of both lungs (Fi-gure 1 c, d). Physical examination was unremarkab-le except for low grade fever (380C) and bilateralcoarse crackles heard in the lung bases with auscul-tation. Laboratory data revealed haemoglobin levelof 14.9 g/dl, white blood cell count of 16400/mm3,

erythrocyte sedimentation rate of 36 mm/hour, al-bumin level of 2.9 g/dl, and total protein level of4.5 g/dl. Urine analysis revealed proteinuria (6g/day). Duodenal biopsy displayed AA type amylo-idosis. Sputum cultures yielded Haemophilus influ-enza and Pseudomonas aeruginosa several times.No acid fast resistant bacilli were grown in anysamples. Paranasal sinus CT revealed maxillary si-nusitis. Immotile cilia syndrome was ruled out byexamination of nasal mucosal biopsy on electronmicroscopy. Serum alpha-1 antitrypsin level andthe sweat chloride test by iontophoresis were nor-mal. Bronchoalveolar lavage and transbronchial bi-opsy were non-diagnostic. The patient underwentopen lung biopsy. The parenchymal nodules seenon CT were found to be thymoma metastasis (Figu-re 2). The histological type of tumor was identicalwith primary lesion. With the probability of thymo-ma associated Good’s Syndrome, serum immunog-lobulin levels were measured and showed low levelof Ig G [438 mg/dl (normal range: 690-1618)] andslightly low level of IgA [62.6 mg/dl (normal ran-ge: 68-375)]. Flow cytometric analysis demonstra-ted reduced level of CD20(+) cells (8% of totallymphocytes) with a normal CD4/CD8 ratio(2.4/1). These findings were consistent with Good’ssyndrome. Fifteen days after surgery, his clinicalcondition deteriorated. He had myasthenic crisis in-duced by a pulmonary infection. After two-monthsof hospitalization in pulmonary intensive care unit,the patient died due to sepsis.

DISCUSSIONThymomas are rare tumors that represent 0.2-1.5 %of all malignancies.1 Although most of the thymo-mas are limited within a capsule and do not infiltra-te adjacent tissues, they are potentially invasive andshould be treated as a malignant disease due to unp-redictable tumor behaviour.1,2 Tumor stage is thesingle factor that has a proven impact on survival.3

Stage III and IV diseases, which represent invasivethymoma, have worse prognosis with 5-year actu-arial survival rates of %67 and %50, respectively.3

Chemotherapy should be added to surgical resecti-on and radiotherapy in Stage IV patients.4 The re-currence rate for invasive thymoma is about 30% ata mean of 5.5 year after the initial resection.5

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The presented case has several unusual aspects.The patient had undiagnosed and therefore untre-ated pulmonary metastases persisting for 3 years.Although the radiological pattern of the nodules didnot suggest tumor spread, open lung biopsy provedthat those nodules were thymoma metastasis. Thisis an extraordinarily long survival for a stage IVuntreated thymoma patient. Because of the rarity ofadvanced thymomas, no large-scale chemotherape-utic clinical trial has ever been conducted but thelongest survival ever reported was about 4.3 to 5years with several chemotherapeutics.4,5

Good’s syndrome occurs in 7-10% of all thymo-mas. It is manifested by hypogammaglobulinemia,reduced or absent B cells, recurrent sinopulmonaryinfections caused by encapsulated microorganismsaccompanied with opportunistic viral and fungalinfections.6 Bronchiectasis can be found in the pati-

ents with Good’s Syndrome. It is more often asso-ciated with noninvasive thymoma unlike the pre-sented case.5,6 The etiology and pathogenesis of thedisease are unknown.6 Our patient had a history ofrecurrent sinopulmonary infections mostly secon-dary to Haemophilus influenzae and Streptococcuspneumoniae. The serum levels of total immuno-gammaglobulins were found to be initially normalexcept for slightly low IgA level. However, on fol-low up, IgG and IgA levels decreased. Importantly,if there is a suspicion of immunodeficiency, repe-ated investigations may be required because manycases with progressive immunodeficiency have be-en reported.6

Amyloidosis has been occasionally reported in as-sociation with acquired hypogammaglobulinemia.Although the pathogenesis is not understood comp-letely, continuous chronic infection seems to be a

UHOD Number: 1 Volume: 21 Year: 2011 59

Figure 1 a, b. HRCT slides show some ectatic bronchi associated with hazy nodulesFigure 1 c, d. Evident nodules present in the lower lobes bilaterally

triggering factor for the deposition of amyloid indifferent tissues.7 Amyloidosis developed in our pa-tient because of inadequate treatment of hypogam-maglobulinemia and related infections for three ye-ars. The association of amyloidosis, hypogammag-lobulinemia and thymoma was first described byConn et al. in their postmortem study of a patientwith thymoma, amyloidosis and hypogammaglobu-linemia.8 Our observation is the second in the lite-rature showing the possible association betweenamyloidosis and Good’s syndrome. Amyloidosismay precede hypogammaglobulinemia and it maybe considered as an additional manifestation of Go-od’s syndrome.8 Moreover, amyloidosis and subse-quent proteinuria may augment hypogamaglobuli-nemia via renal loss, further complicating the situ-ation.

This report emphasizes that thymomas may haveunpredictable courses and even metastastaticthymomas may be associated with a long-term sur-vival. In patients with a history of thymoma, para-

neoplastic syndromes should be considered in dif-ferential diagnosis of newly emerged clinical situ-ations. Additionally, diagnosis of a paraneoplasticsyndrome on follow-up may be a harbinger of per-sistent or recurrent thymoma. Secondly, hypoglo-bulinemia may not appear in the initial course ofGood’s syndrome. Therefore repeat laboratory tes-ting including immunoglobulin levels may be requ-ired in highly suspected cases.

REFERENCES

1. Schmidt–Wolf IG, Rockstroh JK, Schüller H, et al. Ma-lignant Thymoma: Current status of classification andmultimodality treatment. Ann Hematol 82: 69-76,2003.

2. Okumura M, Ohta M, Tateyama H, et al. The WorldHealth Organization histologic classification systemreflects the oncological behaviour of thymoma: A clini-cal study of 273 patients. Cancer 94: 624-32, 2002.

3. Chan JK. Tumors of the lymphoreticular system, inc-luding spleen and thymus. In: Fletcher CD editor. Diag-nostic histopathology of tumors. London: ChurchillLivingstone; 2001: 1270-85.

4. Lara PN. Malignant thymoma: current status andfuture directions. Tumour Review. Cancer Treat Rev26: 127-131, 2000.

5. Park HS, Shin DM, Lee JS, et al. Thymoma. A Retros-pective Study Of 87 Cases. Cancer 73: 2491-2498,1994.

6. Kelleher P, Misbah SA. What is Good’s syndrome? Im-munological abnormalities in patients with thymoma. JClin Pathol 56: 12-16, 2003.

7. Kotilainen P, Vuori K, Kainulainen L, et al. Systemicamyloidosis in a patient with hypogammaglobulinemia.J Inter Med 240: 103-106, 1996.

8. Conn HO, Quintiliani R. Severe diarrhea controlled bygamma globulin in a patient with agammag-lobulinemia, amyloidosis, and thymoma. Ann InternMed 65: 528-541, 1966.

Correspondence

Dr. Asiye KANBAY

Alpaslan Mah.

Alpaslan Apt. No: 25/14

Melikgazi

Kayseri / TURKEY

Tel: (+90.352) 223 97 53

E-mail: kanbaydr@yahoo.com

60 UHOD Number: 1 Volume: 21 Year: 2011

Figure 2. Type B1 thymoma, composed of a preponderanceof small stromal lymphocytes. The epithelial cells are recog-nized by their pale round nuclei. (HE, X100)