Journal of Surgical Oncology 2014;110:341–344

CASE REPORT Primary Pulmonary Classical Hodgkin Lymphoma: A Case Report MICHAEL H. SCHILD, BS,1 WILLIAM W. WONG, MD,1* RICCARDO VALDEZ, 3 AND JOSE F. LEIS, MD, PhD

MD,

2

1 Department of Radiation Oncology, Mayo Clinic Arizona, Scottsdale, Arizona Department of Laboratory Medicine and Pathology, Mayo Clinic Arizona, Scottsdale, Arizona 3 Division of Hematology, Mayo Clinic Arizona, Scottsdale, Arizona

2

Primary pulmonary Hodgkin lymphoma (PPHL) is a rare entity. Most reported cases occurred before the availability of PET scan for accurate staging of the disease. We report a case of PPHL for which PET/CT scan was used and surgery was performed to confirm the diagnosis. A review of cases of PPHL since 1990 suggests that adjuvant chemotherapy and/or radiation therapy after surgical resection of the lung lesions achieve better disease control than surgical resection alone. J. Surg. Oncol. 2014;110:341–344. ß 2014 Wiley Periodicals, Inc.

KEY WORDS: primary pulomary Hodgkin lymphoma; Hodgkin lymphoma of the lung; PET scan for Hodgkin lymphoma

INTRODUCTION Pulmonary involvement by Hodgkin lymphoma (HL) is common and occurs in 15–40% of all cases [1]. The majority of these pulmonary cases present as tracheobronchial or mediastinal and hilar lymphadenopathy. Pulmonary parenchymal involvement is almost always secondary to direct extension of hilar disease into the adjacent lung [2]. In contrast, primary pulmonary Hodgkin lymphoma (PPHL) is extremely rare, with fewer than 100 reported cases [1,3,4]. Radin [5] reviewed the literature that included 61 cases from 1927 to 1986. Most of the cases included in that review occurred in an era when the available diagnostic imaging studies would be considered outdated by today’s standard. Chest X‐ray was the imaging modality employed in many of the cases in Radin’s review. Some of the cases would undoubtedly not be true PPHL if high resolution computed tomography (CT) and positron emission tomography (PET) were used to search for mediastinal and extrathoracic disease. Here we report a case of PPHL for which CT and PET scans were used in the staging evaluation. We also review the cases reported in the literature since 1990, after the review by Radin et al. was published, and include only cases in which there was pathologic confirmation by lung resection, or CT scans and/or PET scan were used as staging studies.

CASE REPORT A 53 year‐old woman presented to her primary care physician with a complaint of pain in the upper chest and back with deep breathing. She denied dyspnea, wheezing, coughing, hemoptysis, fever, night sweat, weight loss, and swollen glands. She had a 35 pack‐year smoking history. Physical examination was remarkable for lung crackles. There was no palpable peripheral lymphadenopathy. No other abnormal masses, or hepatosplenomegaly was detected. Her oxygen saturation was 98% on room air. Laboratory testing revealed the following: hemoglobin 12.5 g/DL, WBC 12,400/mm3, absolute neutrophil count 9,700/ml, and absolute lymphocyte count 1,700/ml, and an erythrocyte sedimentation rate (ESR) of 48. Blood chemistries were unremarkable, and serologic

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testing for Coccidiomycosis immitis and other fungal infections was negative. A chest X‐ray showed a mass in the left upper lobe and a density in the right upper lobe. A chest CT scan revealed a spiculated 6.5 cm  5 cm left suprahilar mass contiguous with the hilum, abutting the left upper mediastinum, and a 4.5 cm calcified mass in the upper right lung. CT‐guided core biopsy of the left lung mass showed acute and organizing pneumonia with foamy macrophages and rare atypical epithelial cells. The epithelial cells stained positively for cytokeratin AE1/AE3, TTF‐1, and Napsin A, but the rare atypical cells were not present on immunostained slides. Repeat chest CT scan three months later showed a stable right upper lobe calcified mass; however, the left upper lobe mass had increased to 9.4 cm. A PET/CT scan showed increase metabolic activity of the left upper lobe mass, with a standard uptake value (SUV) of 22.6 (Fig. 1). The SUV of the calcified right lung mass was normal. There were no other sites of increased metabolic activity in the rest of the body. A second CT‐guided lung biopsy was performed, and that again showed acute and organizing inflammation with scattered atypical cells which were found to be negative for pancytokeratin, but positive for CD15 and CD30. Because of the increasing size of the mass and an inability to make a definitive diagnosis from the CT‐guided core biopsies, the patient underwent a left upper lobectomy and mediastinal lymph node sampling. Three peribronchial lymph nodes, mediastinal lymph nodes, a level VII lymph node, and level IX lymph nodes were excised. Gross examination of the lobectomy specimen revealed an 8 cm  6 cm  4 cm firm mass. Microscopic sections showed the lung

*Correspondence to: William W. Wong, MD, Department of Radiation Oncology, Mayo Clinic Arizona, 13400 E. Shea Boulevard, Scottsdale, AZ 85259. Fax: þ1‐480‐301‐7687. E‐mail: [email protected] Received 26 January 2014; Accepted 22 March 2014 DOI 10.1002/jso.23624 Published online 29 April 2014 in Wiley Online Library (wileyonlinelibrary.com).

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Fig. 1. PET‐CT scan showing a left upper lobe mass with SUV of 22.6 and a calcified right upper lobe mass with no hypermetabolism. mass to consist of multiple lymphoid nodules in a densely sclerotic background. The lymphoid nodules were in turn found to contain a mixture of small lymphocytes, bland macrophages, eosinophils, and a variable number of atypical large uni‐ and binucleate cells with prominent nucleoli, consistent with Hodgkin/Reed–Sternberg (HRS) cells (Fig. 2A,B). Scattered lacunar variants were also found in the sections. Immunostains showed the HRS to be positive for CD15, CD30, PAX‐5 (weak), and MUM‐1, and negative for CD3, CD20, ALK‐1 protein, cytokeratin CAM 5.2, cytokeratin AE1/AE3, epithelial membrane antigen, S‐100 protein, and Melan A. A final diagnosis of classical Hodgkin lymphoma, nodular sclerosis type was rendered for the lung mass. The sampled lymph nodes were negative for lymphoma, and the disease was staged as IE. The patient transferred her care to our hospital after surgery and diagnosis without any additional therapy. A PET scan at one month post‐ surgery was negative. A PET scan three months post‐surgery showed mild increased metabolic activity in the left superior mediastinum, pericarinal region, and AP window, which was interpreted as reactive. The left superior mediastinum revealed a 0.8 cm diameter node with an SUV of 2.9, a 1 cm precarinal node with an SUV of 1.8, and a 0.6 cm AP window node with an SUV of 2.1. A PET scan performed six months after surgery revealed interval worsening of hypermetabolism with an

SUV of 6.4 from a previous value of 2.9 within a lymph node adjacent to the aortic arch which measured 2 cm  1.1 cm (Fig. 3). CT‐guided biopsy of this lymph node was performed and revealed recurrent classical Hodgkin lymphoma. The patient was treated with two cycles of adriamycin, bleomycin, vinblastine, and dacarbazine (ABVD). A re‐ staging PET scan showed a complete response to chemotherapy, with no residual hypermetabolic foci. The patient then received consolidative radiotherapy of 24 Gy in 12 fractions to the site of recurrent disease in the left upper mediastinum. The patient completed the treatment without significant side effects. A follow‐up PET scan at 2 months post radiation therapy was negative for any sign of recurrent disease.

DISCUSSION Pulmonary involvement by HL is common and occurs in 15–40% of all cases. Kern et al. [6] suggested the following criteria for the diagnosis of primary pulmonary Hodgkin lymphoma: (1) histological results must demonstrate Hodgkin disease, (2) the disease must be confined to the lung without hilar lymph node involvement, (3) other pathological conditions that could explain the results must be excluded. Using these criteria, most cases of HL with pulmonary involvement would not be considered as PPHL. There are fewer than 100 cases of PPHL reported in

Fig. 2. A: Nodular lymphoid infiltrates surrounded by sclerosis in lung parenchyma. B: Classical Reed–Sternberg cells and Hodgkin variants with characteristic immunophenotype of HRS cells present within the parenchymal lymphoid nodules. Journal of Surgical Oncology

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Fig. 3. PET‐CT scan showing recurrent Hodgkin lymphoma in para‐aortic lymph node with SUV of 6.4.

the literature, primarily as case reports. Nodular sclerosis (NS) PPHL is the most common variety and comprises 60–70% of PPHL [2,5]. Radin [5] reviewed 61 cases that were reported in the literature. There was a bimodal age distribution, with peak occurrences at 21–30 and 60– 80 years. The typical presenting symptom was a dry cough, and dyspnea, while hemoptysis and wheezing were less common. Systemic symptoms occurred in about half of the patients, and B symptoms in about one third of the patients. PPHL may present as single nodule or mass, multiple nodules, or a cavitated lesion [1,5]. The upper lobes of the lungs are most commonly affected. Factors that correlate with a poorer prognosis include B symptoms, cavitation, and penetration of the pleura [5]. Our case meets each of the criteria for PPHL as suggested by Kern, and it is one of the few reported cases in the modern era in which PET and high resolution CT scans were used for the staging evaluation and for which mediastinal lymph node involvement was excluded by surgery and pathologic evaluation. We have performed a literature search for reported cases of PPHL. Table I summarizes the cases

reported since 1990 and includes only cases evaluated with CT and/or PET scans, and those that involved surgical resection of the lung lesion and mediastinal lymph nodes to pathologically confirm they were truly cases of PPHL [1,3,4,7–12]. A total of 11 cases are included. Selected cases in a published report were not included in our review if they did not meet strict PPHL criteria. A PET scan was done as the staging study for three reported patients, including our patient. Five patients received chemotherapy and three patients received chemotherapy and radiotherapy after diagnosis. Seven of these eight patients were disease‐free, and the one who developed nodal relapse was treated with cisplatin and gemcitabine due to initial misdiagnosis as primary lung cancer. Two patients did not receive additional treatment after resection of the lung disease and both developed nodal relapse. One patient did not receive any treatment and died of pneumonia. For stage 1 classical Hodgkin lymphoma, the standard treatment includes a combination of chemotherapy and radiotherapy, using

TABLE I. Primary Pulmonary Hodgkin Disease: Cases After 1990 Author (year published)

Sex/age

Radiologic/pathologic findings

Treatment

van der Schee[7] Chetty[8] Boshnakova[4]

Outcome

Rodriguez[9] Codrich[10] Kumar[11]

F/31 F/24 M/15 M/42 M/17 M/11 M/36

Bilateral nodular lesions 8 cm LUL mass 10 cm RLL mass 6 cm RLL mass 4.2 and 3.5 cm nodules LLL consolidation RUL mass (PET scan was used)

NED at 3 years NED at 1 year NED at 3 years Died of pneumonia NED at 5 years NED at 6 months Nodal relapse at 10 months

Lluch‐Garcia[1]

M/21

Homma[12] Binesh[3] Schild (current case)

F/58 F/54 F/53

3.5, 5.5, 5.2 cm lesions in left lingula and lower lobe (PET scan was used) 5 cm RML mass Multiple bilateral nodules 8 cm LUL mass (PET scan was used)

CVPPx6 cycles MOPP‐AVB Right lower lobectomy, CT, RT None. Autopsy Wedge resection,CT, RT Left lower lobectomy, CVPP‐ABV, RT Misdiagnosed as lung cancer by FNA, treated with six cycles of cisplatin, gemcitabine ABVDx8 cycles

Right pneumonectomy ABVD Left upper lobectomy

Mediastinal node relapse at 6 years NED at 5 years Mediastinal nodal relapse NED after ABVDx2 and RT

CR after four cycles

CVPP: cyclophosphamide, vincristine, procarbazine, prednisone; NED: no evidence of disease; LUL: left upper lobe; MOPP‐AVB: mustine, oncovin, prednisolone, procarbazine, adriamycin, vinblastine, bleomycin; RLL: right lower lobe; CT: chemotherapy; RT: radiation; LLL: left lower lobe; RUL: right upper lobe; FNA: fine needle aspirate; ABVD: adriamycin, bleomycin, vinblastine, dacarbazine; CR: complete response; RML: right middle lobe.

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2–4 cycles of multi‐agent chemotherapy such as ABVD plus 20–30 Gy of involved nodal radiotherapy. In patients with PPHL, the addition of radiation and/or chemotherapy after complete surgical resection of the tumor appears to reduce the risk of recurrence. Among 37 cases reported in the literature when complete surgical resections were performed, adjuvant treatment was not given in five cases [4,5,7,10,12–14]. Only one of these five patients was recurrence‐free at last follow‐up. In the other 32 cases, additional treatment was given after surgery. The proportion of patients who were disease‐free was: 8/15 patients who had adjuvant irradiation, 5/9 patients who had adjuvant chemotherapy, and 5/8 patients who had adjuvant chemotherapy and irradiation. In our review of 11 cases since 1990, five patients had complete surgical resection of the lung lesions. Two patients did not receive additional therapy and both developed nodal recurrence, while the other three remained disease‐free with the use of chemotherapy and radiation after surgery. In summary, we have reported a case of PPHL for which PET scan and high resolution CT scan were used for staging and evaluation of response to treatment. Our review of literature suggests that additional irradiation and/or chemotherapy appear to reduce the recurrence of disease after complete surgical resection of PPHL.

REFERENCES 1. Lluch‐Garcia R, Briones‐Gomez A, Castellano EM, et al.: Primary pulmonary Hodgkin’s lymphoma. Can Respir J 2010;17:e106– e108. 2. Yousem SA, Weiss LM, Colby TV: Primary pulmonary Hodgkin’s disease. A clinicopathologic study of 15 cases. Cancer 1986;57: 1217–1224. 3. Binesh F, Halvani H, Taghipour S, et al.: Primary pulmonary classic Hodgkin’s lymphoma. BMJ Case Rep 2011;2011.

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4. Boshnakova T, Michailova V, Koss Georgiev C, et al.: Primary pulmonary Hodgkin’s disease—Report of two cases. Respir Med 2000;94:830–8301. 5. Radin AI: Primary pulmonary Hodgkin’s disease. Cancer 1990; 65:550–563. 6. Kern WH, Crepeau AG, Jones JC: Primary Hodgkin’s disease of the lung. Report of 4 cases and review of the literature. Cancer 1961;14:1151–1165. 7. van der Schee AC, Dinkla BA, van Knapen A: Primary pulmonary manifestation of Hodgkin’s disease. Respiration 1990;57:127– 128. 8. Chetty R, Slavin JL, O’Leary JJ, et al.: Primary Hodgkin’s disease of the lung. Pathology 1995;27:111–114. 9. Rodriguez J, Tirabosco R, Pizzolitto S, et al.: Hodgkin lymphoma presenting with exclusive or preponderant pulmonary involvement: A clinicopathologic study of 5 new cases. Ann Diagn Pathol 2006;10:83–88. 10. Codrich D, Monai M, Pelizzo G, et al.: Primary pulmonary Hodgkin’s disease and tuberculosis in an 11‐year‐old boy: Case report and review of the literature. Pediatr Pulmonol 2006;41:694– 698. 11. Kumar R, Sidhu H, Mistry R, et al.: Primary pulmonary Hodgkin’s lymphoma: A rare pitfall in transthoracic fine needle aspiration cytology. Diagn Cytopathol 2008;36:666–669. 12. Homma M, Yamochi‐Onizuka T, Shiozawa E, et al.: Primary pulmonary classical hodgkin lymphoma with two recurrences in the mediastinum: A case report. J Clin Exp Hematopathol 2010;50: 151–157. 13. Ball DG, Herman TE, Variakojis D, et al.: Primary pulmonary Hodgin’s disease: A case report. Arch Intern Med 1982;142:1941– 1943. 14. Zulian GB, Jacot‐des‐Combes E, Aapro MS: Primary pulmonary Hodgkin’s disease and the dilemma of E stage. Eur J Surg Oncol 1986;12:307–310.

Primary pulmonary classical Hodgkin lymphoma: a case report.

Primary pulmonary Hodgkin lymphoma (PPHL) is a rare entity. Most reported cases occurred before the availability of PET scan for accurate staging of t...
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