Primary Mediastinal B-Cell Lymphoma

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Presentation

35M, athlete, no known medical problems.

(all dates modified for HIPAA, relative time spans preserved for instruction)
2023-04-15: Working in the crawl space under his house, developed progressive and eventually severe L arm pain and swelling.
Went to local ED: LUE DVT, put on rivaroxaban. CTPE: +supraclav LN, o/p f/u recommended.
2023-04-20: Called 911 for dyspnea.
2023-04-21: OSH obtained cervical LN core bx: paracortical hyperplasia w focal necrosis
2023-05-05: OSH ER for f/ns and arthralgia, given amox x5d
2023-05-10: Our ER for f/c/ns/n/v, weight loss, chest pain, HA, pruritus.
CT chest: +mediastinal mass, SVC compression w/o critical stenosis, R pleural effusion

Office visit and admission

2023-05-24: HR 130s, dyspneic, plethoric, but able to get around w/o assistance and speak in complete sentences.
Discussed DLBCL vs PMBCL, possibility of cure in either case, recommended admission for expedited w/u and tx start.
Contacted thoracic team for mediastinoscopy, which they accommodated same-day (+chest tube).
Mostly fibrotic tissue, "like chopping through wood".
Wrote for R-EPOCH to start next day.

Admission continued

FDG-PET CT: 9.4x6.3cm mediastinal mass, LAD, diffuse axial skeleton uptake (hyperplasia vs infiltration)
BMBx: NED
Mediastinal bx: results came back a few days later, mostly fibrosis, crush artifact, necrosis
- mature B-cell markers: CD20+, CD45+, PAX5+.
- PMBCL: CD23 patchy ( -ve in DLBCL, cHL, MGZL), CD30 patchy (30% DLBCL, but weak+ in most PMBCL), CD10- (nonGC), equivocal [BCL2/6, c-MYC, MUM1], EBER-
SVC syndrome: much back and forth re SVC stent, RT.
- Ultimately pursued neither, sx slowly improved.

S/sx prevalence at presentation (~%)

Tumor size ≥10cm¹	60
Clinical SVC syndrome¹	55
Radiographic SVC compromise¹	80
Pleural effusion²	50
VTE³	35
B symptoms⁴	30-50

Future directions

PD-L1++
- KEYNOTE-170
  - pembro monotherapy for R/R PMBCL
  - N=53, median LoT 3 (26.4% ASCT)
  - ORR 41.5%, CR 20.8%, mOS 22.3mo, 4y OS 45.3%
- --> frontline chemo + pembro
  - NCT04759586 (investigator's choice + pembro)
Cellular therapy
- e.g. ZUMA-1
  - axi-cel CAR-T
  - N=101, R/R LCL, 8% PMBCL
  - ORR 83%, CR 58%, mOS 25.8mo, 5y OS 42.6%

Bibliography

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Bone marrow involvement¹	2
CNS involvement²	5-10
Marked fibrosis¹	25

Primary Mediastinal B-Cell Lymphoma

Primary Mediastinal B-Cell Lymphoma

Presentation

CT

Presentation continued

Office visit and admission

Admission continued

Subsequent cycles

Questions

Epidemiology

S/sx prevalence at presentation (~%)

Selected clinicopathological features (~%)

Management

Management

Monitoring

Future directions

Bibliography