Pocket Oncology (Pocket Notebook Series), 1st Ed.

THYMOMA AND THYMIC CARCINOMA

Helena A. Yu and Gregory J. Riely

Epidemiology

• ∼400 thymoma, <50 thymic carcinoma (TC) cases annually in US; most common malignancy in the anterior mediastinum

• Most pts present between ages 40–60, slight male predominance, Asian, African-Americans > Caucasians

Pathology/Histology

• Histologic heterogeneity is common, difficult to identify degree of invasion on small biopsies

• IHC: Epithelial cells: +Keratin, +Leu-7, thymic lymphocytes: +LCA, +CD1/3, +CD99

• TC: +CD5, CD 11 7 (C-kit)

• Rare (5%) thymic NETs “carcinoids,” 25% found in a/w MEN

Etiology and Clinical Manifestations

• 40% asx at dx, found incidentally, no known RFs

• Sx: Shortness of breath, cough, CP, trouble swallowing, wt loss, facial swelling/venous distension of neck & CW (SVC syndrome)

• Paraneoplastic syndrome: Almost exclusively w/thymoma

• MG (30–65%) p/w muscle weakness (esp. eyes), dx made w/presence of auto-AB against acetylcholine receptor, tx of MG is thymectomy; other tx: Acetylcholinesterase inhibitor, immunotherapy, plasmapheresis

• Red cell aplasia (5%), dx made w/low reticulocyte count, absent erythroid precursors in BM

• Hypogammaglobulinemia (5–10%) w/typically spindle cell thymoma (Good syndrome), rarely other auto-immune disease including lupus, PM, UC, vitiligo

Molecular Biology

• TC: KIT overexpression by IHC (86%), Mt rare (<10%) (J Pathol 2004;202:375), HER2, & BCL2 overexpression TC >> thymoma (Histopathology 2003;43:165)

• Thymoma/TC: EGFR overexpression common, Mt rare (10/0%) (Jpn J Clin Oncol 2006;36:351)

• Cytogenetics: Alterations in chrom 6p21.3 (MHC locus), 6q25 × 2–3

• TC: Gain chom 1q, 17q, 18 & loss 3p, 6, 16q, 17p

Workup and Staging

• Most commonly used staging system is Masaoka, an alternative is the TNM staging system

• Diff. dx for mediastinal mass: Lymphoma, germ cell, cyst, thyroid tissue

• More than 1 histologic subtype may be found in a given tumor, difficult to determine invasion on a small bx

• W/u includes CT chest; CBC; b-HCG, AFP, thyroid studies as appropriate, optional PET, optional MRI chest/cardiac, PFTs

Prognosis

• Outcomes w/thymoma superior to TC

• Prognostic factors: Resectability, staging, histologic features, age, presence of MG

• Thymomas a/w ↑ risk for 2nd malignancies incl NHL & sarcoma (Int J Cancer 2003;4:546)

Management: Localized Disease

• Complete surgical resection is tx of choice

• No adjuvant Rx for stage 1 disease

• RT: Adjuvant RT for incomplete resection, +margins, may be used w/stage 3 disease, dose 45–60 Gy, ↓ recurrence, s/e: Pulmonary fibrosis, pericarditis

• Chemo: Neoadj for locally invasive or large tumors, plat-based combinations, CAP (CIS, doxorubicin, cyclophosphamide), RR ∼70%, resectability 36–70%, s/e: Fatigue, N/V, alopecia, myelosuppression, alopecia

• Surveillance: Annual chest CT to assess for recurrence

• Recurrence can occur many y later, lifetime surveillance required

Management: Metastatic Disease

• Metastasectomy can lead to good outcome, esp. w/A, B1 histology (J Surg Oncol 2007;95:40)

• Chemo: No large randomized clinical trials. Combination chemo w/↑RR compared to single agent

• CAP w/ORR 50%, CR 10%, mOS 38 mos in thymoma (J Clin Oncol 1994:12:1164)

• Carboplatin/Paclitaxel w/good results in thymoma & TC (in TC: ORR 21.7%, PFS 5 mos) (J Clin Oncol 2011:29:2060)

• Other active agents: CIS/etoposide (J Clin Oncol 1996;14:814), peme, GEM, CIS/irinotecan

Targeted Therapy

• Octreotide: May have activity in octreotide scan + thymoma, CR 5%, PR 25% (J Clin Oncol 2004;22:293)

• Imatinib: Responses in case reports in KIT+ pts, no responses in unselected phase 2 studies (J Thorac Oncol 2009;4:1270)

• Sunitinib: Responses in case reports (3/4 pts w/PR) (Br J Cancer 2010;103:196)

• Cetuximab: Responses in case reports, studies in combination w/chemo ongoing