Initial evaluation and diagnosis of classical Hodgkin lymphoma in adults
- Ann S LaCasce, MD
Ann S LaCasce, MD
- Associate Professor of Medicine
- Harvard Medical School
- Andrea K Ng, MD, MPH
Andrea K Ng, MD, MPH
- Professor, Radiation Oncology, Harvard Medical School
- Brigham and Women's Hospital
- Dana-Farber Cancer Institute
Hodgkin lymphoma (HL, formerly called Hodgkin's disease) is a group of cancers characterized by Reed-Sternberg cells in an appropriate reactive cellular background. An important clinical feature is its tendency to arise within lymph node areas and to spread in an orderly fashion to contiguous areas of lymph nodes. Late in the course of the disease, vascular invasion leads to widespread hematogenous dissemination.
The initial evaluation of the patient with suspected HL is designed to provide information for diagnosis, prognosis, staging, and the selection of treatment. The components of this evaluation are reviewed here. The epidemiology, pathologic features, and staging of HL are discussed separately. (See "Staging and prognosis of Hodgkin lymphoma" and "Epidemiology, pathologic features, and diagnosis of classical Hodgkin lymphoma" and "Overview of the treatment of classical Hodgkin lymphoma in adults".)
Hodgkin lymphoma (HL) has a bimodal age distribution with one peak in the 20s and 30s, and a second peak over the age of 50. It accounts for approximately 10 percent of all lymphomas in economically advanced countries. The epidemiology of HL is discussed in more detail separately. (See "Epidemiology, pathologic features, and diagnosis of classical Hodgkin lymphoma".)
Typical presentation and disease tempo — The majority of patients with classical Hodgkin lymphoma (HL) present with overt disease, most often as an asymptomatic enlarged lymph node or a mass on chest radiograph. However, the presenting symptoms and signs may be relatively nonspecific and more compatible with infection than malignant disease. Occult presentation of HL is unusual, but the incidence of clinically occult disease has been an important influence in the development of therapeutic strategies.
The disease tempo at presentation is variable. B symptoms (fever, night sweats) are present over weeks to months, though other symptoms such as fatigue or lymphadenopathy may be present over many months. Mediastinal masses can be quite large before resulting in discomfort or respiratory symptoms, suggesting that this is not a rapidly growing tumor. In patients being followed after treatment, evidence of recurrence can be seen on imaging within three to six months, but it may be longer before there is clinical evidence of disease.
- Mauch PM, Kalish LA, Kadin M, et al. Patterns of presentation of Hodgkin disease. Implications for etiology and pathogenesis. Cancer 1993; 71:2062.
- Kaplan HS. Hodgkin's Disease, 2nd ed, Harvard University Press, Cambridge, MA 1980.
- Ng AK, Bernardo MP, Weller E, et al. Long-term survival and competing causes of death in patients with early-stage Hodgkin's disease treated at age 50 or younger. J Clin Oncol 2002; 20:2101.
- Good GR, DiNubile MJ. Images in clinical medicine. Cyclic fever in Hodgkin's disease (Pel-Ebstein fever). N Engl J Med 1995; 332:436.
- Gobbi PG, Cavalli C, Gendarini A, et al. Reevaluation of prognostic significance of symptoms in Hodgkin's disease. Cancer 1985; 56:2874.
- Cervantes F, Briones J, Bruguera M, et al. Hodgkin's disease presenting as a cholestatic febrile illness: incidence and main characteristics in a series of 421 patients. Ann Hematol 1996; 72:357.
- Qureshi WA. Intrahepatic cholestatic syndromes: pathogenesis, clinical features and management. Dig Dis 1999; 17:49.
- Dourakis SP, Tzemanakis E, Deutsch M, et al. Fulminant hepatic failure as a presenting paraneoplastic manifestation of Hodgkin's disease. Eur J Gastroenterol Hepatol 1999; 11:1055.
- Atkinson K, Austin DE, McElwain TJ, Peckham MJ. Alcohol pain in Hodgkin's disease. Cancer 1976; 37:895.
- Cavalli F. Rare syndromes in Hodgkin's disease. Ann Oncol 1998; 9 Suppl 5:S109.
- Lucker GP, Steijlen PM. Acrokeratosis paraneoplastica (Bazex syndrome) occurring with acquired ichthyosis in Hodgkin's disease. Br J Dermatol 1995; 133:322.
- Perifanis V, Sfikas G, Tziomalos K, et al. Skin involvement in Hodgkin's disease. Cancer Invest 2006; 24:401.
- Re D, Fuchs M, Schober T, et al. CNS involvement in Hodgkin's lymphoma. J Clin Oncol 2007; 25:3182.
- Morawa E, Ragam A, Sirota R, Nabhan C. Hodgkin's lymphoma involving the CNS. J Clin Oncol 2007; 25:1437.
- de Castro AF, Júnior AS, de Lins e Horta H, et al. Primary intracerebral Hodgkin lymphoma. Br J Haematol 2007; 138:562.
- Gerstner ER, Abrey LE, Schiff D, et al. CNS Hodgkin lymphoma. Blood 2008; 112:1658.
- Graus F, Dalmau J, Valldeoriola F, et al. Immunological characterization of a neuronal antibody (anti-Tr) associated with paraneoplastic cerebellar degeneration and Hodgkin's disease. J Neuroimmunol 1997; 74:55.
- Graus F, Gultekin SH, Ferrer I, et al. Localization of the neuronal antigen recognized by anti-Tr antibodies from patients with paraneoplastic cerebellar degeneration and Hodgkin's disease in the rat nervous system. Acta Neuropathol 1998; 96:1.
- Hammack J, Kotanides H, Rosenblum MK, Posner JB. Paraneoplastic cerebellar degeneration. II. Clinical and immunologic findings in 21 patients with Hodgkin's disease. Neurology 1992; 42:1938.
- Batchelor TT, Platten M, Palmer-Toy DE, et al. Chorea as a paraneoplastic complication of Hodgkin's disease. J Neurooncol 1998; 36:185.
- Caress JB, Abend WK, Preston DC, Logigian EL. A case of Hodgkin's lymphoma producing neuromyotonia. Neurology 1997; 49:258.
- Deodhare S, O'Connor P, Ghazarian D, Bilbao JM. Paraneoplastic limbic encephalitis in Hodgkin's disease. Can J Neurol Sci 1996; 23:138.
- Hughes RA, Britton T, Richards M. Effects of lymphoma on the peripheral nervous system. J R Soc Med 1994; 87:526.
- Plante-Bordeneuve V, Baudrimont M, Gorin NC, Gherardi RK. Subacute sensory neuropathy associated with Hodgkin's disease. J Neurol Sci 1994; 121:155.
- Ferrari P, Federico M, Grimaldi LM, Silingardi V. Stiff-man syndrome in a patient with Hodgkin's disease. An unusual paraneoplastic syndrome. Haematologica 1990; 75:570.
- Briani C, Vitaliani R, Grisold W, et al. Spectrum of paraneoplastic disease associated with lymphoma. Neurology 2011; 76:705.
- Graus F, Ariño H, Dalmau J. Paraneoplastic neurological syndromes in Hodgkin and non-Hodgkin lymphomas. Blood 2014; 123:3230.
- Dabbs DJ, Striker LM, Mignon F, Striker G. Glomerular lesions in lymphomas and leukemias. Am J Med 1986; 80:63.
- Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 15-1983. A 24-year-old man with cervical lymphadenopathy and the nephrotic syndrome. N Engl J Med 1983; 308:888.
- Seymour JF, Gagel RF. Calcitriol: the major humoral mediator of hypercalcemia in Hodgkin's disease and non-Hodgkin's lymphomas. Blood 1993; 82:1383.
- Rieke JW, Donaldson SS, Horning SJ. Hypercalcemia and vitamin D metabolism in Hodgkin's disease. Is there an underlying immunoregulatory relationship? Cancer 1989; 63:1700.
- Shah SJ, Warrier RP, Ode DL, et al. Immune thrombocytopenia and hemolytic anemia associated with Hodgkin disease. J Pediatr Hematol Oncol 1996; 18:227.
- Sierra RD. Coombs-positive hemolytic anemia in Hodgkin's disease: case presentation and review of the literature. Mil Med 1991; 156:691.
- Di Biagio E, Sánchez-Borges M, Desenne JJ, et al. Eosinophilia in Hodgkin's disease: a role for interleukin 5. Int Arch Allergy Immunol 1996; 110:244.
- Teruya-Feldstein J, Jaffe ES, Burd PR, et al. Differential chemokine expression in tissues involved by Hodgkin's disease: direct correlation of eotaxin expression and tissue eosinophilia. Blood 1999; 93:2463.
- Peters MV, Alison RE, Bush RS. Natural history of Hodgkin's disease as related to staging. Cancer 1966; 19:308.
- KAPLAN HS. The radical radiotherapy of regionally localized Hodgkin's disease. Radiology 1962; 78:553.
- Rosenberg SA, Kaplan HS. Evidence for an orderly progression in the spread of Hodgkin's disease. Cancer Res 1966; 26:1225.
- Kaplan HS. On the natural history, treatment and prognosis of Hodgkin's disease. In: Harvey Lectures 1968-69, Academic Press, New York 1970. p.215.
- Klimm B, Franklin J, Stein H, et al. Lymphocyte-depleted classical Hodgkin's lymphoma: a comprehensive analysis from the German Hodgkin study group. J Clin Oncol 2011; 29:3914.
- Cheson BD, Fisher RI, Barrington SF, et al. Recommendations for initial evaluation, staging, and response assessment of Hodgkin and non-Hodgkin lymphoma: the Lugano classification. J Clin Oncol 2014; 32:3059.
- Gobbi PG, Ghirardelli ML, Solcia M, et al. Image-aided estimate of tumor burden in Hodgkin's disease: evidence of its primary prognostic importance. J Clin Oncol 2001; 19:1388.
- Song MK, Chung JS, Lee JJ, et al. Metabolic tumor volume by positron emission tomography/computed tomography as a clinical parameter to determine therapeutic modality for early stage Hodgkin's lymphoma. Cancer Sci 2013; 104:1656.
- Kanoun S, Rossi C, Berriolo-Riedinger A, et al. Baseline metabolic tumour volume is an independent prognostic factor in Hodgkin lymphoma. Eur J Nucl Med Mol Imaging 2014; 41:1735.
- Girinsky T, Aupérin A, Ribrag V, et al. Role of FDG-PET in the implementation of involved-node radiation therapy for Hodgkin lymphoma patients. Int J Radiat Oncol Biol Phys 2014; 89:1047.
- Terezakis SA, Hunt MA, Kowalski A, et al. [¹⁸F]FDG-positron emission tomography coregistration with computed tomography scans for radiation treatment planning of lymphoma and hematologic malignancies. Int J Radiat Oncol Biol Phys 2011; 81:615.
- Specht L, Yahalom J, Illidge T, et al. Modern radiation therapy for Hodgkin lymphoma: field and dose guidelines from the international lymphoma radiation oncology group (ILROG). Int J Radiat Oncol Biol Phys 2014; 89:854.
- Castellino RA, Hoppe RT, Blank N, et al. Computed tomography, lymphography, and staging laparotomy: correlations in initial staging of Hodgkin disease. AJR Am J Roentgenol 1984; 143:37.
- Kaplan HS, Dorfman RF, Nelsen TS, Rosenberg SA. Staging laparotomy and splenectomy in Hodgkin's disease: analysis of indications and patterns of involvement in 285 consecutive, unselected patients. Natl Cancer Inst Monogr 1973; 36:291.
- Weinreb JC, Brateman L, Maravilla KR. Magnetic resonance imaging of hepatic lymphoma. AJR Am J Roentgenol 1984; 143:1211.
- Weissleder R, Stark DD, Elizondo G, et al. MRI of hepatic lymphoma. Magn Reson Imaging 1988; 6:675.
- Braunstein EM. Hodgkin disease of bone: radiographic correlation with the histological classification. Radiology 1980; 137:643.
- CLINICAL PRESENTATION
- Typical presentation and disease tempo
- Asymptomatic lymphadenopathy
- Mediastinal mass
- Systemic symptoms
- - B symptoms
- - Pruritus
- Other nonspecific symptoms and paraneoplastic syndromes
- - Intra-abdominal disease
- - Cholestatic liver disease
- - Alcohol-induced pain
- - Skin lesions
- - Neurologic syndromes
- - Nephrotic syndrome
- - Other
- PATTERNS OF DISEASE PRESENTATION
- Variation by histology
- DIAGNOSTIC EVALUATION
- History and physical examination
- Tissue biopsy
- PRETREATMENT EVALUATION
- Laboratory studies
- Imaging studies
- Cardiac function
- Pulmonary function
- Fertility counseling
- INFORMATION FOR PATIENTS