Primary tracheobronchial anaplastic large cell lymphoma in an 8-year-old child presenting with asthma-like symptoms

Primary tracheobronchial anaplastic large cell lymphoma (ALCL) is very rare. In spite of its rarity, tracheobronchial tumor can cause life-threatening airway obstruction because of its growing site and biological characteristics. Here we represented the clinical and pathological features of a patient with ALCL in the respiratory tract. In September 2009, an 8-year-old female Chinese child who presented with cough, wheezing and severe dyspnea for almost four months. The patient was erroneously diagnosed as asthma on initial presentation and was subsequently treated with antiasthmatic for three months but showed the poor treatment outcomes. Chest computed tomography scan demonstrated an obstructing endoluminal mass in her left main bronchus with atelectasis in the left lung (Figure 1A). As her dyspnea continued to progress, the emergent bronchoscopy was performed promptly after her admission. The result showed the opening of left main bronchus was totally obstructed by a globular smooth mass with broad fundus (Figure 1B). Histopathological examination of the endobronchial biopsy revealed an infiltrate of large atypical lymphoid cells with abundant cytoplasm and pleomorphic nuclei (Figure 1C). Immunophenotypic analyses showed the neoplastic cells expressed CD30 and positive for anaplastic lymphoma kinase (ALK) (Figure 1D and 1E). The markers for CD3, CD7, CD20, CD45RO, CD79a, CD43, Granzyme B, MNF116, CK5/6, LCA, T-cell intracellular antigen-1 (TIA-1) and EMA were all negative. A paraffin section (20 μm thick) was used to detect the clonality of T cell receptor-γ chain (TCR-γ) and immunoglobulin heavy (IgH) using the polymerase chain reaction (PCR) technique. The genomic DNA of the lymphoma cells from the patient exhibited a distinct positive band of the PCR product in 190 bp, which indicating that the lymphoma cells were monoclonal (Figure 1F). Combining all above results, the patient was finally diagnosed as primary tracheobronchial ALCL. Additional staging work-up included a thorough physical examination, abdominal-pelvic computerized tomography, and bone marrow biopsy, all of which were negative for involvement by lymphoma. All laboratory studies including erythrocyte sedimentation rate (ESR), lactate dehydrogenase (LDH), albumin and β2 microglobulin were within normal limits. The patient was staged as having an IEA NHL using the Ann Arbor staging system and was considered as lowintermediate risk International Prognostic Index. Soon after the patient received chemotherapy in the form of CHOP (cyclophosphamide, doxorubicin, vincristine, prednisolone). The patient initially showed good improvement after the two cycle of chemotherapy with resolution of the collapse of the left lung. But due to the economic reason, the patient gave up the succedent therapy. Nevertheless, she still had a disease-free time for almost 12 months after initial treatment.Figure 1. A:: Chest computed tomography demonstrated soft tissue opacity in left main bronchus, with atelectasis in the left lung. B: The bronchoscopic view showing left main bronchus was clogged by a globular smooth neoplasm with broad fundus. C: Photomicrograph of endobronchial biopsy showing closely packed cells with scant cytoplasm and pleomorphic hyperchromatic nuclei with mitotic figures in the vascular lumen and perivascular areas (H&E, Original magnification×400). D: Positive expression of CD30 in ALCL tumor cell (Original magnification×400). E: Positive expression of ALK in ALCL tumor cell (Original magnification×400). F: Immunoglobulin heavy-chain gene rearrangement by polymerase chain reaction. The PCR result of TCR-γ showing a distinct positive band in Lane 5 using DNA from the lymphoma cells of the patient. Lane 1, Marker; Line 2, IgH: sample collected from the lesion of the case showing negative; Lane 3, IgH: B cell lymphoma cell line Raji used as positive control; Lane 4, TCRγ: T celll ymphoma cell line Jurkat used as a positive control; Lane 5, TCRγ: sample collected from the case showing monoclonal pattern.ALCL is a rare disorder which accounts for 3% of non-Hodgkin lymphoma (NHL) in adults while 10%-30% of in pediatric populations.1 ALCL has a unique characteristic of cohesive proliferation of large pleomorphic cells that express CD30 (Ki-1) and was first described by Stein et al in 1985.2 Primary ALCL was divided into systemic and cutaneous ALCL. Primary systemic ALCL are mainly involved in lymph nodes, liver, spleen, soft tissues, bone and other internal organs. However, tracheobronchial involvement is very rare. As the concealment of onset in tracheobronchial tumors, patients usually were asymptomatic or had a minor symptom. With the growth of the tumors, tracheal or bronchus lumen were clogged gradually with the appearance of cough, inspiratory dyspnea and wheezing. With the rupture and bleeding of the tumor, patients would present with hemoptysis. Although a previous literature3 indicated that ALCL were relatively aggressive in all types of lymphomas and usually exhibited as stage III or IV, evaluation of staging in the previous cases of tracheobronchial ALCL showed that as many as 83.3% of the patients was stage I disease. We consider it is might relevant with the site of the tumor. Tracheal stenosis developed in half of the patients and emergency bronchoscopy or tracheal stenting were required immediately. What calls for special attention is that most of patients were initially misdiagnosed as bronchial asthma like our patient due to the non-specific symptoms but finally progressed to the advanced life-threatening diseases. Thus, how to recognize and identify tracheobronchial mass via bronchoscopy was extremely an important task to physicians. We look upon lymphoma, adenoid cystic carcinoma and leiomyoma as three most important diseases which all should be included in the differential diagnosis of a broader base shaped mass involving trachea and bronchial lumen. The bronchoscopic view of mass has much close relationship with its origin of tissue, growth pattern and extent of benign or malignancy. Photomicrograph of the ALCL tumor display large neoplastic cells with abundant cytoplasm and indented, kidney-shaped, or pleomorphic nuclei with many mitotic figures. The tumor cells show cohesive sheets growth pattern in sinuses, which is easily misdiagnosed as metastatic carcinoma and malignant melanoma. Especially, about 40% ALCL tumor cells express epithelial membrane antigen and part of ALCL tumor cells are negative for LCA and positive for LCK. The differential diagnosis should take notice the morphological features of ALCL contain a variable proportion of cells called “hallmark cell” with eccentric, kidney-shaped nuclei often with an eosinophilic region near the nucleus.4 The immunophenotype of ALCL is that of mature, activated T cells that are frequently positive for HLA-DR, CD25, CD30, CD45, and EMA. About 60% of ALCLs express 1 or more T-cell-associated antigens such as CD3, CD43, or CD45RO, and cytotoxic granule proteins are often present.5 The tumor cells are uniform positive for CD30 on the cell membrane and in the Golgi region, which is very important for differential diagnosis. Now the strategy of therapy for patients with primary tracheal lymphoma is inconsistent. Systemic ALCL often has an aggressive clinical course and responds well to treatment with chemotherapy. But as we mentioned before, the treatment for relief of acute airway obstruction is important separated from definitive therapy. To the patients with severe airway stenosis, temporary stenting implantation and reconstruction of airway were deserved to be considered especially in those who could not be tolerant with surgical resection.