Primary pulmonary Hodgkin ’ s lymphoma

Hematology and Pneumology Services, Hospital Arnau de Vilanova, Valencia, Spain Correspondence: Dr Rafael Lluch-Garcia, Hospital Arnau de Vilanova, Hematología, San Clemente 12, 46015, Valencia, Spain. Telephone 34-96-386-8744, fax 34-96-386-8547, e-mail ralluga83@hotmail.com The initial presentation of Hodgkin’s lymphoma as a primary pulmonary injury is very uncommon; fewer than 100 cases have been reported (1,2). In the evolution of Hodgkin’s disease, pulmonary involvement is not rare (3). The appearance of cavitated injuries after treatment is not uncommon; however, detecting them before chemotherapy is exceptional.

T he initial presentation of Hodgkin's lymphoma as a pri- mary pulmonary injury is very uncommon; fewer than 100 cases have been reported (1,2).In the evolution of Hodgkin's disease, pulmonary involvement is not rare (3).The appearance of cavitated injuries after treatment is not uncommon; however, detecting them before chemotherapy is exceptional.

CASE prESEntAtion
A 21-year-old man presented to hospital with a two-month history of productive cough with purulent sputum production.He did not have fever, dyspnea or chest pain, but complained of asthenia and weight loss without anorexia.
The patient had a 2.5 pack-year history of smoking.He was a social drinker and worked in a supermarket.There was no history of dental manipulation, hospitalizations or surgical procedures.
The patient's father had been diagnosed and treated for Hodgkin's disease (a type of nodular sclerosis) 20 years previoulsy, but was now in complete remission.His mother had undergone an operation for esophageal leiomyoma.His two brothers were healthy.
On presentation, the patient's body temperature was 36°C (96.8°F).His blood pressure was 136/76 mmHg, with a heart rate of 110 beats/min.The physical examination was normal.
His hemogram showed a hemoglobin level of 107 g/L; a hematocrit of 31.1%; a white blood cell count of 23.6×10 9 /L (84% neutrophils and 9.3% lymphocytes) with no other abnormalities; and an erythrocyte sedimentation rate of 113 mm/h.A coagulation examination showed a Quick index of 54%; a prothrombin time of 16.6 s; and a partial thromboplastin time of 38.6 s.A special coagulation investigation revealed positive lupus anticoagulant, with no other abnormalities.Biochemistry did not show abnormalities except for a low serum iron level 21.48 µmol/L, a ferritin level of 707.80 pmol/L, an albumin level of 25 g/L and a lactate dehydrogenase level of 301 U/mL.A cavitated lesion appeared in the upper lobe of the left lung on the chest x-ray (Figure 1).After admission, many noninvasive examinations were performed including a series of blood cultures, and pneumococcal and legionella antigen urine cultures.All were negative.Flexible bronchoscopy did not demonstrate airway abnormalities.Bronchial washings showed an abundance of inflammatory macrophages and siderophores, as well as scaly mature cells and cylindrical ciliated cells.Cytology revealed no malignant cells.
Microbiological testing of bronchial alveolar lavage fluid and bronchial washings did not reveal any pathogens.Serology for hepatitis and the assessment for HIV were negative.
Thoracoabdominal computed tomography (CT) revealed three thick-walled cavitated lesions (Figure 2), 35 mm, 55 mm and 52 mm in size in the lingula and upper segment of the left lower lobe without air-fluid levels.Adjacent to the lesions were areas with a ground-glass appearance and air bronchograms.
In the basal segment of the left lower lobe, two pseudonodular injuries 9.6 mm and 3.6 mm in size were observed.In case rePort ©2010 Pulsus Group Inc.All rights reserved r Lluch-Garcia, A Briones-Gomez, E Monzó Castellano, F Sancheztoril, A Lopez, B Brotons. primary pulmonary Hodgkin's lymphoma.Can respir J 2010;17(6):e106-e108.
A 21-year-old man presented to hospital with a two-month history of productive cough with no other symptoms.Radiology revealed a cavitating lesion in the left upper lobe for which a variety of diagnoses were considered.A biopsy revealed primary pulmonary Hodgkin's lymphoma.Primary pulmonary Hodgkin's lymphoma is an uncommon initial presentation; lung lesions usually occur later in the course of the disease.Following diagnosis, the patient began chemotherapy and full remission was achieved.
In spite of mild improvement, the persistence of radiological evidence prompted a reconsideration of the diagnosis.Transthoracic fine-needle aspiration of the lesions showed Reed-Sternberg cells on cytological examination.
A whole-body positron emission tomography (PET)/CT scan was performed.Fludeoxyglucose imaging revealed pathological deposits, which indicated a malignant proliferating mass in the left lung.A small accumulation in the upper left forward lateral rib cage wall with low metabolic activity (maximum standardized uptake value = 1.2) was observed and not specific for malignancy.There were no other significant results.
To confirm the diagnosis, the patient was referred to thoracic surgery for a pulmonary biopsy using video-assisted thoracoscopic surgery, which diagnosed pulmonary Hodgkin's lymphoma nodular sclerosis type E (clinical stage IVB, International Prognostic Index score = 5 [4]).
Following the diagnosis, the patient began an eight-cycle polychemotherapy treatment consiting of adriamycin (doxorubicin), bleomycin, vinblastine and dacarbazine.After the fourth cycle, a PET/CT scan indicated complete remission.

DiSCUSSion
Primary pulmonary Hodgkin's lymphoma (PPHL) is a rare disease.In the study by Radin (5) examining the years between 1927 and 1986, 60 cases of PPHL were reported, particularly in young women.Since the Radin review, seven new cases were published between 1990 and 2003, and five more cases observed up to 2006 can be added to this total (6).
To establish the diagnosis of PPHL, the following criteria must be fulfilled: the disease must be confined to the lung, with or without minimal hilar lymph nodes; histological results compatible with Hodgkin's disease must be present; and other pathological conditions that could explain the results must be excluded (1,2,7).The present case fulfilled all of these criteria.
Pulmonary involvement in Hodgkin's disease can occur in 15% to 40% of cases (3).This is caused by the extension of lymphoid follicles or by peribronchiolar adenopathies adjacent to pulmonary parenchyma (7).Although rare, the occurrence of pulmonary cavitated injuries after chemotherapy treatment have been observed (8,9) .
Because of the wide differential diagnosis, multiple invasive and noninvasive diagnostic investigations are common.Due to these circumstances, in many cases, the injury biopsy that confirms the diagnosis is delayed (7).
Nodular sclerosis of the Hodgkin's disease variety is the most frequent histological subtype found in the PPHL presentation, which occurs more frequently in women than in men.The mixed cellularity subtype has also been described (6,11,12).
Sputum cytology or bronchial brushings may reveal Reed-Sternberg cells and establish the diagnosis of pulmonary Hodgkin's disease, thereby avoiding the need for more aggressive procedures (11).On the other hand, these cells are not common, and cells similar to Reed-Stenberg cells may be seen in non-Hodgkin's lymphoma, melanoma and some carcinomas (12) .
Transthoracic fine-needle aspiration is a simple and useful method to establish the initial diagnosis in many cases (9), and is more useful in patients with a history of Hodgkin's disease in   whom pulmonary recurrence is suspected (12).The inmunohistochemistry performed for the assessment of citoqueratin, S100 protein and CD30 in the extracted samples can help in the differential diagnosis when sufficient material is obtained (1).In our case, an immunohistochemistry study was successful; the atypical cells obtained from the pulmonary biopsy showed intense positivity for CD30, CD15 and p53, and some exhibited CD20 positivity.Ki-67 also existed.Ki-67 also existed.The accompanying lymphocytes were positive for CD3 and CD5.In spite of this, according to the majority of authors, a pulmonary biopsy is almost always necessary to confirm the diagnosis of PPHL (7,8).In the present case, the pulmonary biopsy was obtained using video-assisted thoracoscopic surgery, a technique associated with the fewest number of complications of open lung biopsy.
A literature review found no cases in which a family history of Hodgkin's disease was described.The risk of lymphoma has been reported as being five times higher in members of a nuclear family, which does not necessarily mean that Hodgkin's disease is a hereditary disease.Familial Hodgkin's disease is only present in 5% of cases (13).
Early assessment of therapeutic response by the end of fludeoxyglucose PET/CT imaging after the fourth cycle of treatment in our patient showed complete remission.Despite this, however, he continued to receive the requisite eight cycles of treatment due to the number of risk factors that constitute the International Prognostic Scoring System for advancedstage Hodgkin's lymphoma, which reports a progression-free survival of five years in 42% of cases (14,15).rEFErEnCES

Figure 1 )
Figure 1) X-ray showing a cavitated injury in the upper lobe of the left lung

Figure 2 )
Figure 2) Computed tomography scan of the chest showing three thick-walled cavitated injuries in the left lower lobe of the lung