Variable Problems in Lymphomas

VOLUME 23 䡠 NUMBER 31 䡠 NOVEMBER 1 2005

JOURNAL OF CLINICAL ONCOLOGY

D I A G N O S I S

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O N C O L O G Y

Variable Problems in Lymphomas midway through the procedure, the patient desaturated acutely, and was immediately intubated by an anesthetist with an endotracheal tube of 7.5 Fr. However, due to extensive airway compression by the tumor, adequate ventilation could not be achieved by conventional positive pressure ventilation. Examination of the airway by rigid bronchoscopy showed extensive compression of major airways from the distal 4 cm of the trachea, to the left main bronchus, with a residual patency of 20%. The right main bronchus was reduced to a slit-like orifice. A 12 ⫻ 40-mm silicone stent (Endoxane; Cometh Laboratoire, La Ciotat Cedex, France) was deployed into the left main bronchus. However, due to the severity of the obstruction, the stent remained compressed following deployment. As we were unable to overcome the airway obstruction, she remained difficult to ventilate, developing hypotension, respiratory acidosis, with a pCO2 of 80 mmHg, and hypoxemia. She was thus placed on venovenous extracorperal membrane oxygenation (ECMO) as a temporary measure to maintain her oxygenation and acid-base status. Despite her gas exchange being maintained by the ECMO circuit, she remained on the ventilator, with tidal volumes of 120 mL, positive end expiratory pressure of 15 cm water, with a respiratory rate of eight breaths per minute to prevent lung atelectasis. Her peak airway pressures were 30 cm water. Chemotherapy (intravenous dexamethasone 40 mg for 4 days, cyclophosphamide 750 mg, and vincristine 2 mg) was started immediately. Plans were made for radiotherapy if the patient did not respond adequately to the chemotherapy. She was also supported with low doses of intravenous dopamine infusion.

Burkitt’s Lymphoma Presenting With Central Airway Obstruction

CASE 1.

A previously healthy, nonsmoking 21-year-old female student presented with cough, progressive dyspnea, and wheezing of 2 month’s duration. The dyspnea and wheezing were most pronounced in the supine position, and she was thus unable to lie flat in bed. This was not associated with fever or weight loss. A chest x-ray revealed an anterior mediastinal mass further evaluated on a computed tomography scan of the chest. The mass occupied the anterior and superior mediastinum, encompassing the left brachiocephalic vein, and compressing the lower trachea, left main bronchus, left upper lobe, and pulmonary arteries (Fig 1). There was no other associated adenopathy. Her lactate dehydrogenase level was elevated at 535 U/L. Both alpha-feta protein (2.5 U/L) and beta-human chorionic gonadotrophin (⬍ 2.0 U/L) levels were unremarkable. At initial presentation, she had an Eastern Cooperative Oncology Group performance status of 1, reduced air entry in both lungs with occasional wheezing, and she had neither any palpable lymphadenopathy nor organomegaly. Her blood pressure was normal at 110/70 mmHg, and pulse oximetry done with intranasal oxygen of 4 L/min in an upright posture was 98%. However, the oximetry promptly decreased to 84% when the patient assumed a supine posture. The patient underwent an open biopsy of the mediastinal mass under local anesthesia by a cardiothoracic surgeon (H.N.K.). On frozen section, the mass was confirmed to be a malignant lymphoma. However,

Fig 1.

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Diagnosis in Oncology

cardiopulmonary bypass, but not below the therapeutic levels for most pathogens.

Forty-eight hours later, the patient’s peak airway pressures dropped from 65 mmHg to 35 mmHg, and tidal volumes improved from 120 to 500 mL. She was weaned off ECMO after 3 days and was successfully extubated 6 days following surgery. Her post-ECMO recovery period was complicated by pneumonia, which was treated with intravenous cefepime and metronidazole, while supported with subcutaneous filgastrim. A final histology report confirmed the diagnosis of Burkitt’s lymphoma. Immunostains were strongly positive for CD20 and bcl-6. CD10 also stained positive, MIB-1 fraction was 95%, and fluorescent in situ hybridization was positive for 8:14 translocation. Further computed tomography staging and bone marrow studies were negative for disease elsewhere. The patient responded well to combination chemotherapy with “hyperCVAD” (hyperfractionated cyclophosphamide, vincristine, doxorubicin, dexamethasone). Recognition and diagnosis and of a compromised airway from a mediastinal tumor is vital, especially for chemosensitive tumors like lymphomas. The multidisciplinary approach to the management of our difficult case was crucial in ensuring a good outcome. Large mediastinal masses that compress the trachea, bronchi, and pulmonary arteries cause unpredictable variations in pulmonary mechanics,1 with flattened flowvolume loops on spirometry and ventilation/perfusion abnormalities.2-5 General anesthesia should be avoided. It causes collapse of the airway distal to the endotracheal tube because of muscle relaxation and loss of negative airway pressure associated with awake ventilation.6 Difficulties in intubation because of anatomic distortion of the airway, ventilation difficulties because of high airway pressures from trapped lung, and perfusion abnormalities because of compression of the pulmonary vasculature were all present in our patient. The use of portable cardiopulmonary bypass was crucial in management. Radiotherapy was not required because of the rapid response to chemotherapy. Portable cardiopulmonary bypass has been used as an emergency intervention in a variety of applications, including profound hypothermia,7 cardiopulmonary arrest due to coronary heart disease,8-10 pulmonary embolism,11 trauma,12 and upper-airway obstruction.13 A search of MEDLINE revealed one other case14 in which chemotherapy was administered while the patient was on portable cardiopulmonary bypass support. It is not known if cardiopulmonary bypass affects the plasma concentration levels of chemotherapy thus making it less effective. A small study15 on 10 patients showed that plasma vancomycin levels dropped by as much as 40%, when patients were on

Su Pin Choo and Darren W.T. Lim National Cancer Centre, Singapore, Singapore

Constance P.L. Lo Singapore General Hospital, Singapore, Singapore

Heng Nung Koong and Miriam Tao National Cancer Centre, Singapore, Singapore

Chong Hee Lim National Heart Centre, Singapore, Singapore

Authors’ Disclosures of Potential Conflicts of Interest The authors indicated no potential conflicts of interest. REFERENCES 1. Vander Els NJ, Sorhage F, Bach AM, et al: Abnormal flow volume loops in patients with intrathoracic Hodgkin’s disease. Chest 117:12561261, 2000 2. Prakash UB, Abel MD, Hubmayr RD: Mediastinal mass and tracheal obstruction during general anesthesia. Mayo Clin Proc 63:1004-1011, 1988 3. Pullerits J, Holzman R: Anaesthesia for patients with mediastinal masses. Can J Anaesth 36:681-688, 1989 4. Robie DK, Gursoy MH, WJ Pokorny: Mediastinal tumors: Airway obstruction and management. Semin Pediatr Surg 3:259-266, 1994 5. Lefor AT: Perioperative management of the patient with cancer. Chest 115:165S-171S, 1999 (suppl 5) 6. Sibert KS, Biondi JW, Hirsch NP, et al: Spontaneous respiration during thoracotomy in a patient with a mediastinal mass. Anesth Analg 66:904-907, 1987 7. Antretter H, Dapunt OE, Mueller LC, et al: Portable cardiopulmonary bypass: Resuscitation from prolonged ice-water submersion and asystole. Ann Thorac Surg 58:1786-1787, 1994 8. Dembitsky WP, Moreno-Cabral RJ, Adamson RM, et al: Emergency resuscitation using portable extracorporeal membrane oxygenation. Ann Thorac Surg 55:304-309, 1993 9. Kurusz M, Zwischenberger JB: Percutaneous cardiopulmonary bypass for cardiac emergencies. Perfusion 17:269-277, 2002 10. Newsome LR, Ponganis P, Reichman R, et al: Portable percutaneous cardiopulmonary bypass: Use in supported coronary angioplasty, aortic valvuloplasty, and cardiac arrest. J Cardiothorac Vasc Anesth 6:328-331, 1992 11. Mattox KL, Feldtman RW, Beall AC Jr, et al: Pulmonary embolectomy for acute massive pulmonary embolism. Ann Surg 195:726-731, 1982 12. Hill JG, Bruhn PS, Cohen SE, et al:, Emergent applications of cardiopulmonary support: A multiinstitutional experience. Ann Thorac Surg 54:699-704, 1992 13. Rosa P Jr, Johnson EA, Barcia PJ: The impossible airway: A plan. Chest 109:1649-1650, 1996 14. Stewart AS, Smythe WR, Aukburg S, et al: Severe acute extrinsic airway compression by mediastinal tumor successfully managed with extracorporeal membrane oxygenation. Asaio J 44:219-221, 1998 15. Miglioli PA, Merlo F, Grabocka E, et al: Effects of cardio-pulmonary bypass on vancomycin plasma concentration decay. Pharmacol Res 38:275278, 1998

DOI: 10.1200/JCO.2005.95.159 ■ ■ ■

Sarcoidosis Mimicking Progressive Lymphoma

CASE 2.

A 56-year-old woman presented with postmenopausal bleeding. A pelvic mass was palpable. Computed tomography (CT) scan demonstrated a uterine mass, right iliac

adenopathy, and bilateral hydronephrosis. Surgical exploration demonstrated a large uterine mass, infiltration of the round ligaments bilaterally, bilateral ureteral dilation, and dense adherence of the bladder to the lower uterine segment and cervix. The patient underwent a supracervical hysterectomy, bilateral salpingo-oophorectomy, and bilateral

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Hollister et al

ureterolysis. Pathology showed diffuse large B-cell lymphoma (Fig 1) extensively infiltrating the pelvic peritoneum, uterus, and both fallopian tubes. Postoperative CT staging showed bilateral hydronephrosis, debulking of the pelvic mass, and postoperative changes. Chest CT showed 1- to 2-cm right paratracheal nodes and a 1.5-cm left aortopulmonic window node. There was no hilar adenopathy. An [18F] fluorodeoxyglucose positron emission tomography (FDG-PET) scan (Fig 2) demonstrated mutiple foci of abnormal tracer activity in both hilar and the right paratracheal area. Tracer activity in the pelvis was mild and felt consistent with the postoperative state. There was no definite nodal positivity in the retroperitoneum. Hydronephrosis was again evident. Serum creatinine and lactate dehydrogenase were within normal limits. Bone marrow and spinal fluid examinations were negative. The patient was treated with four cycles of rituximab, cyclophosphamide, vincristine, doxirubicin, and prednisone, and intrathecal methotrexate with G-CSF support on a 2-week cycle. After the fourth cycle, follow-up CT scans demonstrated that the mediastinal adenopathy was slightly smaller, although persistent. The residual soft tissue mass in the pelvis had diminished, and the hydronephrosis had resolved. A follow-up FDG-PET scan (Fig 3) revealed interval increased activity in the mediastinum. The maximum standard uptake value of these lesions had approximately doubled. Also noted was increased bone marrow activity felt to be a result of chemotherapy. There was no abnormal activity below the diaphragm. The patient completed two additional cycles of treatment without difficulty. A third PET scan (not shown) obtained 4 weeks after cycle 6 showed the same findings as the second scan. Mediastinoscopy was performed for tissue diagnosis. The pathology (Fig 4) showed noncaseating granuloma consistent with sarcoidosis. Fungal and mycobacterial cultures were negative. Serum angiotensinconverting enzyme level was 3 (range, 9 to 67 U/L). The patient remains in clinical complete remission after chemotherapy. She has had no symptoms related to her sarcoidosis and has required no treatment for it.

Fig 2.

The association of sarcoidosis and malignant lymphoma was described in 1979.1 In two cases, the lymphoma preceded the diagnosis of sarcoidosis.2 In 1996, a patient was described whose preexisting sarcoidosis was exacerbated by chemotherapy for non-Hodgkin’s lymphoma.3 Two additional patients reported to have nonHodgkin’s lymphoma developed active sarcoidosis during or immediately after combination chemotherapy.4 Our patient is another example. In all of these cases, treatment of the lymphoma appears to have exacerbated pre-existing, occult sarcoidosis. This is particularly unexpected because sarcoidosis itself is treated with similar

Fig 1.

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Fig 4.

ing used more commonly in the management of patients with malignant lymphoma.9 Similar to lymphoma, sarcoidosis can cause increased FDG uptake in mediastinal lymph nodes.10-12 Abnormal uptake of FDG caused by sarcoidosis is indistinguishable from that caused by lymphoma. Therefore, the possibility that abnormal PET scans of lymphoma patients could be due to sarcoidosis and not malignancy must be considered. In cases of apparent progressive lymphoma during or subsequent to combination chemotherapy, biopsy confirmation should be considered. Tissue confirmation of sarcoidosis was critical for the further management of our case.

Fig 3.

immunosuppressive therapies, including corticosteroids and, in refractory cases, chemotherapy itself.5 Sarcoidosis has also been described after treatment for solid tumors, including radiation and chemotherapy for testicular cancer,6 chemotherapy for osteosarcoma,7 and interferon for renal cell cancer.8 FDG-PET scanning is be-

Dickerman Hollister Jr, M. Sung Lee, Richard N. Eisen, and Christopher Fey Greenwich Hospital, Yale New Haven Health System, Greenwich, CT

Carol S. Portlock Memorial Sloan-Kettering Cancer Center, New York, NY © 2005 by American Society of Clinical Oncology

Authors’ Disclosures of Potential Conflicts of Interest Although all authors completed the disclosure declaration, the following author or immediate family members indicated a financial interest. No conflict exists for drugs or devices used in a study if they are not being evaluated as part of the investigation. For a detailed description of the disclosure categories, or for more information about ASCO’s conflict of interest policy, please refer to the Author Disclosure Declaration and the Disclosures of Potential Conflicts of Interest section in Information for Contributors. Authors

Employment

Leadership

Consultant

Stock

Carol S. Portlock

Honoraria

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Other

Idec (A); Genentech (A) Dollar Amount Codes

(A) ⬍ $10,000

(B) $10,000-99,999

REFERENCES 1. Brincker H: The incidence of malignant tumors in patients with respiratory sarcoidosis. Br J Cancer 29:247-251, 1979 2. Brincker H: The sarcoidosis-lymphoma syndrome. Br J Cancer 54: 467-473, 1986 3. Keohane GSG, Savin JA, Tidman MJ, et al: The sarcoidosis-lymphoma syndrome: Acceleration of the cutaneous sarcoidosis during chemotherapy of lymphoma. Acta Derm Venereol 76:251-253, 1996

(C) ⱖ $100,000

(N/R) Not Required

4. Kornacker M, Kraemer A, Leo E, et al: Occurrence of sarcoidosis subsequent to chemotherapy for non-Hodgkin’s lymphoma: Report of two cases. Ann Hematol 81:103-105, 2002 5. Baughman RP, Ohmichi M, Lower EE: Combination therapy for sarcoidosis. Sarcoidosis Vasc Diffuse Lung Dis 18:133-137, 2001 6. Trum DL, Ettinger DS, Feldman MJ, et al: Sarcoidosis and sarcoid-like lesions: Their occurrence after cytotoxic and radiation therapy of testis cancer. Arch Intern Med 141:37-38, 1981

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Parekh et al

11. Yasuda S, Shohisu A, Ide M, et al: High fluorine-18 labeled deoxyglucose uptake in sarcoidosis. Clin Nucl Med 21:983-984, 1996 12. Yamada Y, Uchida Y, Tatsumi K, et al: Flurine-18-flurodeoxygenase and carbon-11-methionine evaluation of lymphadenopathy in sarcoidosis. J Nucl Med 39:1160-1166, 1998

7. Sybert A, Butler TP: Sarcoidosis following adjuvant high-dose methotrexate therapy for osteosarcoma. Arch Intern Med 138:488-489, 1978 8. Abdi EA, Nguyen G, Ludwig RN, et al: Pulmonary sarcoidosis following interferon therapy for advanced renal cell carcinoma. Cancer 59:896-900, 1987 9. Elstrom R, Guan L, Baker G, et al: Utility of FDG-PET scanning in lymphoma by WHO classification. Blood 101:3875-3876, 2003 10. Lewis PJ, Salama A: Uptake of fluorine-18-flurodeoxyglucose in sarcoidosis. J Nucl Med 35:1647-1649, 1994

DOI: 10.1200/JCO.2005.08.107

■ ■ ■

The incidence of Burkitt’s lymphoma is increased approximately 200- to 300-fold in patients with HIV infection.1 Spontaneous regression of endemic Burkitt’s lymphoma is rare in immunocompetent individuals. Burkitt and Kyalwazi2 initially reported three cases of biopsyproven Burkitt’s lymphoma of the breast, orbit, and jaw, respectively, that spontaneously regressed for up to 7 years without any treatment. Spontaneous regression in six of eight cases of maxillary Burkitt’s lymphoma was reported by David and Burkitt after injections of “septiceme,” a mixture of hexamine iodomethylate, hexamine, sodium benzoate, and saccharose.3 Fass et al4 reported 12 patients with Burkitt’s lymphoma treated with one to two intradermal injections of autologous tumor extract, of whom seven had tumor regression associated with positive delayed hypersensitivity reactions. With regard to HIV-associated disease, Sarkodee-Adoo et al5 reported temporary regression of Burkitt’s lymphoma associated with improvement in immunologic status after antiretroviral therapy alone; however, the patient had a clonally distinct recurrence 3 months later. Antiretroviral therapy–associated regression has also been reported with primary CNS lymphoma,6 plasmablastic lymphoma of the oral cavity,7 and T-cell non-Hodgkin’s lymphoma.8 Regression of primary CNS lymphoma after treatment with steroids has also been described.9 Our patient did not have any change in antiretroviral therapy or CD4 count and never received steroids. Although we do not advocate a “watchful waiting” approach, our experience

Spontaneous Regression of HIV-Associated Burkitt’s Lymphoma of the Cecum CASE 3.

A 47-year-old man with a history of HIV infection presented with bloody diarrhea and 30-lb (13.6-kg) weight loss. He had been taking stavudine, ritonavir, saquinavir, and didanosine for the last 4 years, and his CD4 count was 350 U/L with an undetectable viral load. His only previous HIV-related illness was oral thrush. Physical examination was significant for bilateral axillary adenopathy measuring 1 to 2 cm. Computed tomogrpahy (CT) of the abdomen and pelvis showed a cecal mass, hepatomegaly, and renal cysts. Colonoscopy revealed a circumferential multilobated mass above the ileocecal junction (Fig 1A). Biopsy revealed Burkitt-type high-grade B-cell lymphoma (Fig 2A). Biopsy of right axillary adenopathy showed reactive hyperplasia, but no evidence of lymphoma. Bone marrow biopsy showed no evidence of lymphoma, and the serum lactose dehydrogenase level was not elevated. The patient sought alternative opinions and returned 3 months later. Repeat CT scan of the abdomen showed regression of the cecal mass. Colonoscopy confirmed a significant decrease in the mass (Fig 1B), and biopsy showed a florid reactive polyclonal B- and T-lymphocyte hyperplasia without evidence of lymphoma (Fig 2B). His antiretroviral regimen was unchanged, CD4 count was 330 U/L, and viral load was still undetectable at this time. The patient is alive and without evidence of disease 5 and a half years after initial presentation.

Fig 1.

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Fig 2.

indicates that spontaneous regession may rarely occur for selected patients with HIV-associated Burkitt’s lymphoma. Samir Parekh Albert Einstein Cancer Center, Montefiore Medical Center, Bronx, NY

Tiffany Hebert and Howard Ratech Department of Pathology, Montefiore Medical Center, Bronx, NY

Joseph Sparano Albert Einstein Cancer Center, Montefiore Medical Center, Bronx, NY © 2005 by American Society of Clinical Oncology

Authors’ Disclosures of Potential Conflicts of Interest The authors indicated no potential conflicts of interest. REFERENCES 1. Cote TR BR, Rosenberg PS, et al: Non-Hodgkin’s lymphoma among people with AIDS: Incidence, presentation and public health burden. Int J Cancer 73:645-650, 1997

2. Burkitt DP, Kyalwazi SK: Spontaneous remission of African lymphoma. Br J Cancer 21:14-16, 1967 3. David J, Burkitt D: Burkitt’s lymphoma: Remissions following seemingly non-specific therapy. BMJ 4:288-289, 1968 4. Fass L, Herberman RB, Ziegler J: Delayed cutaneous hypersensitivity reactions to autologous extracts of Burkitt-lymphoma cells. N Engl J Med 282:776-780, 1970 5. Sarkodee-Adoo C, Pittarelli L, Jaffe E, et al: Regression and clonally distinct recurrence of human immunodeficiency virus related Burkitt-like lymphoma during antiretroviral therapy. Leuk Lymphoma 42:1125-1131, 2001 6. McGowan JP, Shah S: Long-term remission of AIDS-related primary central nervous system lymphoma associated with highly active antiretroviral therapy. Aids 12:952-954, 1998 7. Nasta SD, Carrum GM, Shahab I, et al: Regression of a plasmablastic lymphoma in a patient with HIV on highly active antiretroviral therapy. Leuk Lymphoma 43:423-426, 2002 8. Fatkenheuer G, Hell K, Roers A, et al: Spontaneous regression of HIV associated T-cell non-Hodgkin’s lymphoma with highly active antiretroviral therapy. Eur J Med Res 5:236-240, 2000 9. Al-Yamany M, Lozano A, Nag S, et al: Spontaneous remission of primary central nervous system lymphoma: Report of 3 cases and discussion of pathophysiology. J Neurooncol 42:151-159, 1999

DOI: 10.1200/JCO.2005.08.079

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