Lung involvement due to anaplastic lymphoma kinase (ALK) anaplastic large cell lymphoma is very unusual. We describe the case of a HIV-1 infected patient who developed it.
A 44-year-old male was admitted in our hospital with 20 days of dyspnea, mucous expectoration and fever. He presented a previous history of HIV-1 infection diagnosed 10 years previously. Currently, he had been without antiretroviral therapy and control for the last 12 months. Then, his last T-CD4+ cell count and viral load were 311 cells/μl and 315 copies/ml, respectively.
On admission, he was hemodynamically stable, afebrile and with pulse arterial oxygen saturation of 100% (FiO2 0.28). The physical exam revealed 3 cm hepatomegaly, and soft, mobile and less than 1 cm supraclavicular lymphadenopathies. Chest radiograph showed a left paramediastinal mass, two small nodular alveolar infiltrates in the left pulmonary apex and a bilateral interstitial pattern (Fig. 1a). Laboratory studies revealed C-reactive protein 4.49 mg/dl, γ-glutamyltransferase/alkaline phosphatase 59/122 IU/l, lactate dehydrogenase 465 IU/l and sodium 127 mEq/l. Empiric antibiotic treatment was started. Blood and sputum cultures, as well as cryptococcal antigenemia, were negative. CD4+ T-cell count and viral load were 98 cells/μl and 444 200 copies/ml, respectively. A fibrobronchoscopy with bronchoalveolar lavage was performed: PCR for Mycobaterium tuberculosis, cytomegalovirus and herpes simplex virus was negative. A biopsy of a supraclavicular adenopathy showed abscessified granuloma with negative stains for mycobacteria.
After 2 weeks of admission, all microbiological results were negative and the patient had not presented any improvement. A computed tomography scan showed a left upper lobe cavitating lesion, bilateral lung nodules, mediastinal necrotic adenopathies, multiple hepatic lesions and celiac and retroperitoneal adenopathies, one of them with necrotic core. A tru-cut biopsy of one hepatic lesion was suggestive of infiltrative lymphocytic syndrome. Empiric treatment with isoniazid, clarithromycin, levofloxacin and rifampicin was then added.
During the next 72 h, the pulmonary infiltrates progressed (Fig. 1b) and the patient finally required invasive mechanical ventilation. Finally, a lung transthoracic biopsy was performed, showing ALK− anaplastic large cell lymphoma (CD30+ cytotoxic pleomorphic peripheral T-cell lymphoma) together with acute lung damage images (Fig. 1c–g). Treatment with cyclophosphamide, doxorubicin and methylprednisolone was started. However, the patient presented refractory distributive shock with multiorgan failure and died 75 days after admission.
The spectrum of lymphoid neoplasms related to AIDS and HIV-infection mainly includes systemic non-Hodgkin lymphomas. They are usually of B-cell origin, being T-cell lymphomas much less frequent (1–3%) . The peripheral T-cell lymphomas are uncommon and difficult to diagnose in HIV-infected patients in advanced stages because of the cellular changes in their immune system. Among peripheral T-cell lymphomas, the anaplastic large cell lymphoma (ALCL) is the second most frequent. It is characterized by pleomorphic large cells, with a sinus growth pattern and CD30 antigen expression. It can be classified into cutaneous or systemic ALCL, with lymphatic and extralymphatic involvement. The latter can be ALK+ or ALK−, depending on whether they show activation of the ALK protein, a transmembrane receptor tyrosine kinase of the insulin receptor superfamily .
In the general population, the ALK+ ALCL usually presents with B symptoms and node involvement, although extranodal involvement has also been described. They usually respond better to treatment with a favourable prognosis.
On the contrary, ALK− ALCL exhibits almost exclusively extranodal involvement, and a very aggressive clinical course . Lung involvement is unusual. The most common radiological expression is parenchymal consolidating masses or areas of uneven borders. Cavitating, endobronchial masses, mediastinal and pleural involvement are unusual [4,5].
As far as we know, there are less than 40 cases of ALCL in HIV-infected patients described in the literature to date [6–8]. It is more frequent in men and the mean age of diagnosis is 38 years. Frequency increases with the progression of the illness to AIDS, with a median CD4+ T-cell count of 83 cells/μl upon diagnosis. Response to treatment is poor, with a median overall survival of 5 months .
Patient features are similar to those of non-HIV infected patients, although some authors describe greater lung involvement without concomitant mediastinal mass . To the best of our knowledge, there are only eight previous cases in the literature with lung involvement. Only one showed fatal respiratory failure as in our case [10–13].
In summary, ALCL with lung involvement is an unusual, aggressive clinical entity, which generally involves severely immunodepressed HIV-infected patients. When these patients present subacute pulmonary infiltrates without microbiologic isolations and with no response to antibiotic treatment, this diagnosis should be ruled out.
Conflicts of interest
There are no conflicts of interest.
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