A 34-year-old female with no medical history originally presented with
hoarseness and a choking sensation in November 2007.
She noted an episode of epistaxis from her left nostril in January 2008.
On physical examination, she demonstrated a unilateral swelling of her left
CT of her neck showed extensive soft tissue swelling around the right
orbit surrounding the optic nerve and near the vocal cords. Cervical and
supraclavicular lymph nodes also were noted.
She underwent left supraclavicular lymph node fine-needle aspiration,
which showed a B-cell lymphoma that could have represented a nodal marginal
zone B-cell lymphoma with secondary extension into the orbit, although the
reverse extension to lymph nodes of the primary extranodal marginal zone B-cell
lymphoma of the orbit could not be ruled out.
Histopathology revealed a population of monotonous small lymphocytes
with mildly irregular nuclei contour and clumped chromatin, positive for CD20
and bcl-2, and negative for CD23, CD10, CD43, CD5, cyclin D1 and bcl-6.
Monoclonal B-cell population was CD19+, CD10–, CD23–, CD5–,
Kappa+ and Lambda–. Flow cytometry of the lymph node showed CD19+, CD20+,
CD22–, CD10–, CD23–, CD5–, Kappa+ and Lambda–. Staging
CT scans showed left supraclavicular lymph nodes, enlarged right internal
mammary lymph nodes, splenomegaly, breast nodules and subcutaneous soft tissue
Figure 1. (CT orbits from Feb. 15, 2008). Axial and coronal reformats from the initial orbital CT show crescentic focus of soft tissue density in the superolateral right orbit, largely inseparable from the lateral rectus muscle (arrow). Multiple other right retrobulbar abnormalities were seen, consistent with clinical suspicion of lymphoma.
Images: M. Ghesani, MD, reprinted with permission.
Bone marrow biopsy was negative. A left laryngeal mass biopsy on Jan.
28, 2008, showed minute fragmented respiratory mucosa with atypical lymphoid
infiltrate suspicious for lymphoma. A left false vocal cord biopsy showed
squamous and respiratory mucosa with atypical lymphoid infiltrate suspicious
for lymphoma, and a biopsy of the left lingual tonsil showed fragments of
mucosa involved by large B-cell lymphoma.
Immunohistochemically showed atypical large cell infiltrate, strongly
and diffusely positive for B-cell marker CD20 and bcl-2; CD10– and cyclin
D1–. Lab work revealed lactate dehydrogenase 199 IU/L and uric acid 5.6
mg/dL. Liver function tests were normal; C-reactive protein 5.23 mg/L,
beta-2–microglobulin 3.2 g/mL, serum protein electrophoresis and
immunofixation — no monoclonal protein.
PET/CT on Jan. 29, 2008, showed supraclavicular lymphadenopathy and a
hypermetabolic nodule in the right breast, mediastinal and groin lymph nodes,
cervical lymph nodes and subcutaneous soft tissue nodules. She was started on
prednisone 60 mg daily.
After detailed discussion, she started R-CVP. She received a total of
six cycles. Post-treatment PET/CT on Aug. 5, 2008, showed no evidence of
disease. She then was treated with four cycles of maintenance rituximab
Interim PET scans did not show any signs of active lymphoma. However,
follow-up PET/CT on March 14, 2011, showed a focal mass posterior left of the
midline lower back measuring 1.3 cm × 0.8 cm with a standardized uptake
value (SUV) of 1.6 at the level of the L5 vertebra.
Figure 2. Staging PET/CT from March 27, 2008 (Figure 2a), shows enhancing right optic nerve thickening and abnormal corresponding hypermetabolic activity (arrow), highly suspicious for lymphomatous involvement. The same scan also demonstrated hypermetabolic right nasopharyngeal soft tissues and hypermetabolic right breast nodules, as well as hypermetabolic lymph nodes in the neck, chest, abdomen and pelvis, all suspicious for lymphomatous involvement. A follow-up scan on May 29, 2008 (Figure 2b), after chemotherapy, showed resolution of right optic nerve thickening with no residual hyperbolic activity, consistent with excellent response to treatment. Previous findings in the neck, chest, abdomen and pelvis showed similar response.
A new, second nodular focus measuring 7 mm × 4 mm was seen at the
level of the left gluteal muscle.
Because of suspicion for disease recurrence, the patient underwent
restaging PET/CT on June 2, 2011. The previously seen subcutaneous soft tissue
nodule in the left lower back/gluteal area had increased in size to 1.3 cm
× 1.3 cm, with SUV of 3.2.
There were new adjacent subcutaneous soft tissue nodules overlying the
gluteus muscle measuring 1.8 cm × 1.5 cm and 0.9 cm × 1 cm, with
SUV of 2.9. A left gluteal nodule had increased to 1 cm × 0.7 cm, with
SUV of 3. There was no radiographically significant or hypermetabolic
lymphadenopathy. There was no evidence to suspect recurrence of right optic
She underwent a biopsy of this soft tissue nodule, which showed
extranodal marginal zone lymphoma.
Extranodal marginal zone lymphoma, also called low grade B-cell lymphoma
of mucosa-associated lymphoid tissue (MALT), is an extranodal lymphoma that
arises in a number of epithelial tissues, including the stomach, salivary
gland, lung and small bowel.
For treatment purposes, extranodal MALT is separated into those
developing in the stomach (gastric MALT) and those developing in nongastric
extranodal locations (nongastric MALT). This distinction is primarily based
upon the role of Helicobacter pylori in the development of gastric MALT
and the efficacy of H. pylori eradication in the treatment of gastric
Figure 3a. Follow-up PET/CT from March 14, 2011, shows a new hypermetabolic subcutaneous nodule (arrow) in the left lower back/gluteal soft tissues. The patient had no history of subcutaneous injections in that area, and the possibility of lymphomatous involvement could not be excluded. There was no evidence of recurrence in the right orbit or anywhere else in the body.
Figure 3b. A repeat scan on June 22, 2011), showed an increase in size, number and hypermetabolism of subcutaneous left lower back/gluteal soft tissue nodules. Subsequent percutaneous biopsy revealed B-cell lymphoma.
Pretreatment evaluation should include a thorough physical exam,
determination of the patient’s performance status by the ECOG or Karnofsky
performance scales, lab testing — including a complete blood count with
differential and platelet count — chemistries with liver and renal
function and electrolytes, and lactate dehydrogenase level. Patients also
should be tested for hepatitis B before the use of rituximab therapy. Imaging
should include a contrast-enhanced CT scan of the chest, abdomen and pelvis.
Patients with multifocal disease should have a bone marrow aspiration and
Locoregional radiation therapy is the primary treatment option for
limited-stage disease. Surgery typically is used for diagnostic purposes only,
but may play a role in the treatment of tumors in areas not conducive to
radiation therapy (eg, lungs). The addition of adjuvant chemotherapy or
antibiotic therapy has not demonstrated improved DFS or OS. There are
occasional patients with stage I disease who are not ideal candidates for
radiation therapy and may be initially observed closely.
The treatment of patients with advanced-stage nongastric extranodal
marginal zone lymphoma is not clearly defined, and most data in this population
come from retrospective series or extrapolation of data from other indolent
- Anacak Y. Int J Radiat Oncol Biol Phys. 2012;82:315-320.
- Fung CY. Int J Radiat Oncol Biol Phys. 2003;57:1382-1391.
- Goda JS. Cancer. 2010;116:3815-3824.
- Goda JS. Int J Radiat Oncol Biol Phys. 2011;81:e659-666.
- Isobe K. Int J Radiat Oncol Biol Phys. 2007;69:1181-1186.
- Son SH. Int J Radiat Oncol Biol Phys. 2010;77:86-91.
- Tsang RW. Int J Radiat Oncol Biol Phys. 2001;50:1258-1264.
- Tsang RW. J Clin Oncol. 2003;21:4157-4164.
For more information:
- Munir Ghesani, MD, is an attending radiologist at St.
Luke’s-Roosevelt Hospital Center and Beth Israel Medical Center, an
associate clinical professor of radiology at Columbia University College of
Physicians and Surgeons, and a HemOnc Today section editor. Amit Patel, MD, is
a fellow in hematology/oncology at St. Luke’s-Roosevelt Hospital. Sam
Altman, MD, is a resident in radiology at St. Luke’s-Roosevelt Hospital
Center. Drs. Ghesani, Patel and Altman report no relevant financial