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<Case
History>
A 72 year-old woman visited the OPD
with a chief complaint of left neck masses noted for 1 month.
She was a patient of chronic renal insufficiency and
hypertrophic cardiomyopathy, for which she took regular
medications at the OPD. She felt several masses at the left
neck since one month ago. The masses gradually enlarged, but
they were painless. There was no fever, decrease of appetite,
night sweating or obvious change in her body weight. She did
not have any symptoms of upper airway or GI symptoms such as
nasal congestion, sore throat, ear stuffiness, dysphagia,
odynophagia, hoarseness or cough. However, she felt
malaise these days with marked reduction of her daily
activities. She was a housewife and did not travel in
recent years. She was not exposed to animals. Physically,
the patient looked chronically ill, with clear consciousness
and orientation. The BP was128/84 mmHg; pulse 82/min, regular;
BT 36.8°C; respiration rate 14/min. The conjunctiva was mildly
pale. Three rubbery, non-tender, and movable masses of size
about 3 cm were felt at the lower left neck, above the
clavicle, and lateral to the sternocleidomastoid muscle. At
the left forearm there was an AV fistula, which was created
for future hemodialysis. There were no other palpable masses
all over the body. The liver and spleen were not felt. The
heart beat was regular, and a grade 2/6 systolic murmur was
audible along the left sternal border. The chest was clear.
There was no peripheral edema. The muscle power of the
extremities was symmetric and full. The nasopharyngeal area
was checked by an ENT doctor and no abnormal findings were
detected. The lab data showed Hb 9.4 g/dl; platelet count
140,000/μL, WBC 4500/μL with normal classification; MCV 92 fl;
LDH 780 U/L; Cr 5.0 mg/dl; BUN 68 mg/dl. The liver functions
and electrolytes (Na, K, Ca) were normal. Bone marrow biopsy
was negative for lymphoma involvement, but showed
hypocellularity. Neck, chest and abdominal CT were arranged
and a biopsy of the neck masses was performed. The pathology
report was diffuse large B cell lymphoma, and there were no
other tumors noted in the CT. One week later, the patient was
brought to the OPD again for the pathology and radiology
reports. But this time the patient presented with confusion
and disorientation, without focal neurological abnormalities.
Emergent lab data showed hypercalcemia (Ca 11.6 mg/dl). She
was transferred to the ward for further management. Emergent
hemodialysis via the fistula was performed, using low calcium
dialysate. The calcium level dropped to 8.8 mg/dl with
normalization of the consciousness. Chemotherapy (R-CHOP) with
half dose of cyclophosphamide, full-dose adriamycin,
vincristine, and prednisolone, plus full-dose anti-CD20
(rituximab) was given soon thereafter. The masses shrank
completely at the 10th day
post-chemotherapy. The white blood cell count dropped to
200/μL with absolute neutrophil count approaching zero at the
12th day. Granulocyte colony
stimulating factor (G-CSF) was administered, and the patient's
white count returned to normal 6 days later, without fever
episodes. Follow-up renal, liver and heart functions were
similar to the baseline. She was discharged smoothly. One
major complication of the treatment was profound prostration
and peripheral neuropathy. Subsequently, she received one
course of R-COP, two courses of rituximab plus full-dose
prednisolone. No further chemotherapy was given based on the
performance status of the patient. The lymphoma remained in
complete remission 1 year after the last course of
chemotherapy.
<Analysis>
Diagnosis:Neck masses should be differentiated
among neoplastic, inflammatory, or congenital. For this
patient over 70 years old with recent growth of the left neck
masses, neoplastic process is more likely, and the congenital
nature can almost be ruled out. The inflammatory nodes can be
due to various infections in the head and neck regions. But
the lack of tenderness or symptoms around upper GI and
respiratory systems makes inflammation less likely. For
patients older than 40 years old with neck masses persistent
for more than 1 month, neoplasms should be ruled out until
proved otherwise. The texture of the masses can be very
informative. Stony hard and fixed lesions suggested metastatic
carcinoma; while rubbery, relatively unfixed masses favor a
diagnosis of lymphoma. Otolaryngologists should be consulted
to rule out head and neck cancers. Supraclavicular lesions
might originate from GI, lung, breast or GU tracts, and
appropriate exams are indicated to rule out these
possibilities. For this patient, metastatic carcinoma is less
likely based on the nodal texture. Rather, otolaryngologists
were consulted to check the head and neck region and for node
biopsy. Pathological exams can help determine the type (B cell
or T cell) and aggressiveness (low grade or high grade) of the
lymphoma, as shown in this case.
Assessment of disease
extent:Staging of lymphoma includes CT scanning
of the neck, chest, abdomen and pelvic regions, and bone
marrow biopsy. For highly aggressive lymphoma such as
lymphoblastic lymphoma, CSF study is also mandatory. Factors
included in International Prognostic Index (IPI) score: age
(> 60 years old), performance status (ECOG >= 2),
LDH level (above normal limit), Ann-Arbor stage (stage III or
IV), and extranodal involment (>= 1) should be clarified,
because of the correlation of the IPI score and survival. This
patient presented with high-intermediate risk and localized
aggressive lymphoma.
Management of acute
complications:An acute complication is hypercalcemia,
which is possibly due to lymphoma and the poor renal function.
This complication should always be suspected in malignancy
patients presenting with consciousness change. Mainstay of
management is treatment of lymphoma, but acute amelioration in
this patient is necessary due to the high value of calcium
level. Because of the poor renal function, fluid challenge is
risky. Therefore, we chose emergent hemodialysis to lower her
calcium level, and quickly started definitive anti-tumor
chemotherapy.
Determine the definitive
therapy:Although radiation therapy alone might be
sufficient to cure a significant portion of localized
aggressive lymphoma, several factors do not favor this
modality of treatment in this patient (Lester et al., 1982;
Levitt et al., 1985). First, the clinical staging may not be
correct. Occult distal involvement of lymphoma may escape
detection unless laparotomy and pathological staging are
performed. Radiation alone surely is not enough if occult
disease is present elsewhere. Secondly, hypercalcemia and high
LDH are both poor prognostic factors, and studies did not
suggest radiation therapy alone in these settings. Therefore,
chemotherapy with or without adjuvant local radiation is the
treatment of choice for this patient (Miller and Jones, 1983;
Vokes et al., 1985) .
Choosing the regimen of
chemotherapy: CHOP (cyclophosphamide,
adriamycin, vincristine, and prednisolone) is commonly used
because of simplicity, and possibly equal efficacy among other
regimens. Recent data showed addition of anti-CD20 antibody
(rituximab) yielded better overall survival to elder patients
of high-grade lymphoma (Coiffier et al., 2002).
Therefore, we chose R-CHOP as the initial chemotherapy. The
addition of G-CSF can shorten the duration of neutropenia and
hospital stay, although no clear benefit in patient survival
has been proved (Crawford et al., 1991; Dombret et al.,
1995). Because of the good response of the tumor, and
the grade 4 neutropenia , we omitted adriamycin in the second
course. Subsequent treatment included only rituximab plus
prednisolone, because the patient could not tolerate the
neuropathy and she exhibited profound prostration after
previous cytotoxic therapy. An advantage of this patient is
the localized disease and good response to therapy. Radiation
therapy can be applied once neck masses reappear. Fortunately,
this did not happen.
Adjustment of dosages in patients with
poor renal function:This is a patient with very poor renal
function. Adriamycin, vincristine and prednisolone can be
given in full doses in patients with poor renal function.
Cyclophosphamide has to be cut in half. There is little
experience in using rituximab in patients of renal impairment.
Several case reports indicated full dose of rituximab was safe
for patients with renal failure (Ghijsels et al., 2004; Tokar
et al., 2004). We confirmed these observations in this
patient.
Cardiotoxicity of
adriamycin:This patient has hypertrophic
cardiomyopathy without evidence of heart failure. Adriamycin
can cause dose-related cardiomyopathy, resulting in decrease
of LV ejection fraction and congestive heart failure. This
patient should be safe upon adriamycin administration based on
the absence of heart failure, in spite of her hypertrophic
cardiomyopathy.
<Reference>
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Herbrecht, R., Tilly, H., Bouabdallah, R., Morel, P., Van Den
Neste, E., Salles, G., Gaulard, P., Reyes, F., Lederlin, P.
and Gisselbrecht, C. (2002) CHOP chemotherapy plus rituximab
compared with CHOP alone in elderly patients with diffuse
large-B-cell lymphoma. N Engl J Med, 346, 235-242.
Crawford, J., Ozer, H., Stoller, R.,
Johnson, D., Lyman, G., Tabbara, I., Kris, M., Grous, J.,
Picozzi, V., Rausch, G. and et al. (1991) Reduction by
granulocyte colony-stimulating factor of fever and neutropenia
induced by chemotherapy in patients with small-cell lung
cancer. N Engl J Med, 325, 164-170.
Dombret, H., Chastang, C., Fenaux, P.,
Reiffers, J., Bordessoule, D., Bouabdallah, R., Mandelli, F.,
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colony-stimulating factor in elderly patients after treatment
for acute myelogenous leukemia. AML Cooperative Study Group. N
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Ghijsels, E., Lerut, E.,
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Lester, J.N., Fuller, L.M., Conrad,
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Levitt, S.H., Lee, C.K., Bloomfield,
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Miller, T.P. and Jones, S.E. (1983)
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Tokar, M., Rogachev, B., Levi,
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819-820.
Vokes, E.E., Ultmann, J.E., Golomb,
H.M., Gaynor, E.R., Ferguson, D.J., Griem, M.L. and Oleske, D.
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Case Discussion
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