Solitary extramedullary plasmacytoma (EMP) accounts for a small fraction of plasma-cell neoplasms and rarely involves the conjunctiva. Distinguishing localized EMP from ocular adnexal lymphomas and reactive plasmacytosis is crucial, as management and prognosis differ substantially. We report a CD56-negative, lambda-restricted conjunctival EMP in a 27-year-old male with baseline Bence–Jones proteinuria, successfully treated with organ-sparing surgery plus orbital radiotherapy (RT) and maintained in remission at one year.

This single-patient case review used prospectively recorded clinical data. Diagnostic workflow comprised ophthalmologic examination, complete blood count and chemistry, serum protein electrophoresis (SPEP) with immunofixation, 24-hour urine immunofixation, bone marrow aspirate/biopsy with immunohistochemistry (IHC), whole-body PET/CT, and brain/orbital MRI as indicated. Response was assessed clinically, biochemically (paraprotein clearance), and radiologically.

A painless, 1.5-cm vascular conjunctival mass was excised. Histology showed dense plasmacytic infiltration. IHC: CD38+, CD138+, lambda light-chain restriction, CD56−; B- and T-cell markers were non-diagnostic for lymphoma. SPEP showed no serum M-spike, while urine immunofixation revealed monoclonal lambda (Bence–Jones) positivity. Bone marrow morphology and flow cytometry demonstrated normal hematopoiesis without clonal plasma cells. PET/CT showed avid uptake confined to the conjunctival lesion; minor uptakes in stomach/sacrum lacked structural correlates. CRAB criteria were absent.

Definitive local therapy consisted of adjuvant orbital RT (40 Gy in 20 fractions) after complete excision. Treatment was well tolerated. At 3 months, urine monoclonal lambda resolved; at 12 months, there was no local recurrence or new systemic disease clinically or on surveillance imaging/labs.

Key learning points include: (i) Localization and phenotype—conjunctival EMP is exceptional; CD56 negativity, while not universal, may be more frequent in extramedullary disease and can correlate with reduced bone tropism, supporting a truly localized process. (ii) Diagnostic clarity—lambda restriction with CD38/CD138 positivity and absent marrow disease distinguishes EMP from ocular adnexal MALT lymphoma and IgG4-related disease. (iii) Therapeutic strategy—organ-sparing RT at 40–45 Gy achieves excellent control in EMP; here, 40 Gy sterilized the lesion and eliminated Bence–Jones proteinuria, implying the conjunctival clone was the source of the paraprotein. (iv) Surveillance—despite remission, EMP carries a risk of progression to multiple myeloma; our young patient remains on structured follow-up (periodic CBC, renal function, calcium, SPEP/IFE, serum free light chains, and symptom-directed imaging).

This CD56-negative conjunctival EMP in a young adult underscores that meticulous staging can confirm true localization, enabling conservative surgery plus moderate-dose orbital RT to deliver durable biochemical and clinical remission. The rapid clearance of Bence–Jones lambda after RT highlights the curative potential of localized therapy while reinforcing the need for vigilant long-term monitoring.