The Case of Mistaken Identity

by Shripad Banavali, MD, Tata
Memorial Hospital, Mumbai, India

Figure 1: This computerized tomographic scan of the upper thorax shows a large anterior mediastinal mass (M) and compression and deviation of the trachea to the left (T). The CT scan was performed before surgery. Figure 1

The patient, a 13-year-old male, presented on May 3, 2001 to a local hospital in a small city near Mumbai. He had a seven-month history of breathlessness on exertion which had significantly worsened in the days immediately prior to admission to the local hospital. At the time of admission, he had no palpable lymphadenopathy or organomegaly, and routine laboratory tests were normal. A 2-D echocardiogram performed at this time showed normal heart function, but revealed a mediastinal mass that was confirmed by a CT scan (Fig 1). The surgeon at the local hospital, who was not a specialist in oncology, made a presumptive diagnosis of thymoma. The patient underwent a median sternotomy and excision of the mass on May 5. The diagnosis made by the local pathologist was thymoma: lymphocytic type. Within one week from surgery and prior to discharge from the hospital the patient developed bilateral cervical lymphadenopathy. He was referred to the Tata Memorial Hospital (TMH) for evaluation and pathology review.

The patient was admitted to the Thoracic Surgical Unit of the TMH on May 29. Physical examination revealed bilateral gross cervical lymphadenopathy. His blood counts were within normal limits. He underwent a fine needle aspiration biopsy of one of the lymph node masses and samples previously obtained from the thymic mass were reviewed. The diagnoses reported by the pathologist at TMH were suggestive of lymphoblastic lymphoma (LL) in the lymph node, but this diagnosis was confirmed when the sample from the excised thymic mass was reviewed. The tumor cells in the thymic mass were shown to be of T cell type and expressed CD3. Unfortunately, the patient and his family returned to their hometown before receiving the pathology reports. The patient was then lost to follow-up.

A month later, on June 29, the patient presented to TMH and was promptly referred to the Pediatric Oncology Unit. The patient had clinically deteriorated and had increased breathlessness. On physical examination, multiple, moderately sized (2 x 3 cm each) lymph nodes were palpable in the neck, one in the right axilla, and there was bilateral testicular enlargement. The liver and spleen were normal in size. Routine laboratory tests revealed an elevated white blood count of 153,000 per mm3 with 43% circulating lymphoblasts and high serum lactic acid dehydrogenase and uric acid levels (7060 U/L and 8.2 mg%, respectively). A chest x-ray revealed mediastinal widening. Extensive retroperitoneal lymphadenopathy and bilateral enlarged testes were confirmed by ultrasound examination. A bone marrow aspirate showed 81% leukemic blasts of L1 morphology and T cell immunophenotype. An examination of the cerebrospinal fluid was also positive for leukemic blasts.

A diagnosis of acute lymphoblastic leukemia (ALL) of T cell immunophenotype was made and the patient was immediately admitted to the Pediatric Oncology Unit and prepared for chemotherapy. He was started on protocol MCP841, a standard protocol for the treatment of ALL in India. At the completion of induction therapy, the patient achieved complete remission. He went on to receive cranial and testicular radiation with 2340 cGy each, followed by re-induction and consolidation therapy. He is currently in his second maintenance cycle and will continue maintenance therapy until he has completed a total of six cycles.

This case is an example of the natural history of the evolution of lymphoblastic lymphoma into acute T-cell leukemia (the distinction between these "diseases" is arbitrary, being based on the degree of bone marrow involvement). This case also demonstrates some of the reasons for delays in the diagnosis and treatment of pediatric oncology cases in developing countries. The lack of knowledge of pediatric oncology by the surgeon at the local hospital who initially evaluated the patient was evident in the preliminary differential diagnosis. In patients of this age who present with mediastinal masses, the most common diagnoses include Hodgkin's disease, lymphoblastic lymphoma/leukemia and large B cell lymphoma. In a younger patient, germ cell tumor and neuroblastoma would need to be considered; thymoma is rare in children and adolescents and often associated with an underlying disease. A standard diagnostic procedure would be CT-guided or fine needle biopsy, thus avoiding surgery.

Because he had not considered other possible diagnoses, such as lymphoma, the surgeon did not order supplementary immunohistochemistry tests on the biopsy material. This resulted in an inaccurate diagnosis and also caused the patient to undergo an unnecessary major surgical procedure (albeit, the correct procedure for thymoma) which entailed significant risk given the size of the mass and the presence of tracheal compression (cardiac arrest, or the need for prolonged ventilation after surgery are potential complications). It is often worth incurring the small additional expense of potentially definitive diagnostic tests in order to ensure that an accurate diagnosis is made rather than using valuable resources in giving incorrect treatment – which can be expensive and sometimes carries significant risk. Although the surgeon correctly referred the patient to TMH after the development of lymphadenopathy, there was poor communication with the patient and his family, which led to them being unaware of the diagnosis and resulted in the patient becoming lost to follow-up. The delay in obtaining an accurate diagnosis and in starting appropriate therapy resulted in disease progression, including the development of CNS and testicular disease, and a consequently worse prognosis, requiring more prolonged therapy. We strongly recommend that children with tumors are referred immediately to a specialized center where appropriate expertise in diagnosis and therapy exists.