Diagnostic Evaluation

Initial diagnostic evaluation of HL is aimed at pathological confirmation, followed by additional evaluations to fully stage the patient. These assessments not only guide the patient's therapeutic management, but also impact prognosis. Patients with palpable lym-phadenopathy should undergo an excisional biopsy in order to obtain an adequate diagnostic specimen. Fine needle aspirations are not sufficient to distinguish between classical HD and other CD30+ lymphomas including anaplastic T-cell lymphoma and diffuse large cell lymphoma. In addition, information regarding the subtype of HL (nodular sclerosing, mixed cellularity, lymphocyte rich, or lymphocyte depleted) may provide some guidance to expected clinical features.

The currently recommended diagnostic/staging work-up for patients with newly diagnosed HL is outlined in Table 72.1. The initial history and physical examination should address the presence or absence of B symptoms (defined as drenching night sweats, fever exceeding 38°C/100.4°F, or unexplained weight loss of

Table 72.1 Recommended diagnostic work-up for patients with HL

History and physical examination B symptoms (The absence or presence of fever (>38°C), unexplained weight loss (>10% body weight), or night sweats)

EtOH intolerance

Pruritis

Fatigue

Performance status

Examination of nodes, Waldeyer's ring, liver, and spleen

Laboratory

CBC, differential, platelets Erthrocyte sedimentation rate (ESR) Lactate dehydrogenase (LDH)

Liver function tests (ALT, AST, bilirubin, alkaline phosphatase)

Albumin

BUN, creatinine

Serum/urine pregnancy test (in women of childbearing age) HIV (if risk factors or unusual clinical presentation)

Imaging studies Chest X-ray

CT chest/abdomen/pelvis (neck, in selected cases) PET/gallium scanning (in selected cases)

Additional procedures

Bone marrow biopsy (bilateral, preferred) Semen/oocyte cryopreservation

EtOH, ethanol; CBC, complete blood count; ALT, alanine transaminase; AST, aspartate transaminase; BUN, blood urea nitrogen, CT, computed tomography; PET, positron emission tomography.

at least 10% of the total body weight within the last 6 months), alcohol intolerance, pruritus, fatigue, performance status, and an examination of nodes, spleen, liver, and Waldeyer's ring. On physical examination, involved lymph nodes typically are nontender, rubbery, or firm. Large lymph nodes may coalesce, forming fixed, matted masses.

Initial laboratory testing should include a complete blood count with differential, erythrocyte sedimentation rate (ESR), lactate dehydrogenase (LDH), liver function tests, albumin, blood urea nitrogen (BUN), and creatinine. Elevated white blood cell count, lym-phopenia, anemia, hypoalbuminemia, and an elevated ESR all have prognostic value in the treatment of HL (Table 72.2).2122 In selected patients, HIV and pregnancy testing may also be indicated. Chest X-ray and CT scanning of the chest/abdomen/pelvis should be used to assess both the bulk and sites of disease at initial presentation. Patients presenting with signs or symptoms of naso-oropharyngeal involvement, such as the Waldeyer's ring, may require CT or magnetic resonance imaging (MRI) scans of the head and neck, to appropriately evaluate response. Bulky disease, usually defined as a mediastinal mass ratio (maximum

Prognostic factors in HL21,

Early-stage HL22

Advanced-stage HL21

EORTC criteria Large mediastinal mass Mediastinal mass ratio (MMR) >1/3

Tumor/nodal mass >10 cm Age >50

ESR >50 without B symptoms or >30 with B-symptoms >4 sites of involvement GHSG criteria Large mediastinal mass Mediastinal mass ratio (MMR) >1/3

Tumor/nodal mass >10 cm Extranodal disease ESR >50 without B symptoms or >30 with B symptoms >3 sites of involvement

Albumin <4 g/dL Hemoglobin <10.5 g/dL Male

Age >45 years Leukocytosis (WBC>15,000/mm3) Lymphopenia (Lymphocyte count <8% of WBC, or <600/mm3) Stage IV disease

CCTG or ECOG criteria

Low risk disease: LPHL or NS HL, age <40, ESR <50, <3 regions of involvement

High risk disease: All other histologies excluding LPHL or NS HL, bulky disease >10 cm, ESR >50, age >40, >3 regions of involvement

EORTC, European Organization for Research and Treatment of Cancer; GHSG, German Hodgkin Lymphoma Study Group; CCTG, Canadian Clinical Trials Group; ECOG, Eastern Co-Operative Oncology Group; LP HL, lymphocyte-predominant Hodgkin's lymphoma; NS HL, nodular sclerosing Hodgkin's lymphoma.

width of the tumor mass divided by maximum intrathoracic diameter) exceeding 1/3 or any single nodal/tumor mass exceeding 10 cm, is also an unfavorable prognostic factor. Other imaging techniques including PET or gallium scanning may be helpful, particularly in patients with large mediastinal masses or in the setting of indeterminant lesions on CT. These modalities will be discussed later in this chapter. Finally, bone marrow biopsy should be performed to complete the staging work-up. Bone marrow involvement has been reported in 5-15% of patients at diagnosis, and is frequently associated with the presence of B symptoms.2324

All patients should also be counseled regarding the risks of tobacco use during and after therapy, and fertility issues should be addressed. Specifically, with adriamycin, bleomycin, vinblastine, dacarbazine (ABVD) and Stanford V chemotherapy, there appears to be little effect on fertility, although this has not been studied exhaustively.2526 However, intensive regimens including bleomycin, etoposide, adri-amycin, cyclophosphamide, prednisone, procar-bazine (BEACOPP) or other combination salvage therapies (including, but not limited to, ifostamide, carboplatin, etoposide (ICE), dexamethasone, cytara-bine, cisplatin (DHAP), and etoposide, methylpre-duisolone, cytarabine, cisplatin (ESHAP)), followed by hematopoietic stem cell transplantation (SCT) for those patients who relapse, frequently affect fertility, and semen/oocyte cryopreservation is advised for those patients contemplating future parenthood. Finally, due to the high risk of second malignancies reported after combination chemotherapy and/or radiotherapy for classical HL,27 28 all patients should be advised about the need for continual follow-up and screening mammograms in the posttreatment period.

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