Follicular lymphoma (FL) is a germinal-center B-cell neoplasm that typically expresses CD10/BCL6 and lacks CD5. CD5-positive FL is uncommon and may mimic mantle cell lymphoma (MCL), creating critical diagnostic and therapeutic implications. We report an older male with a history of resected cutaneous squamous cell carcinoma (SCC) who presented with a new inguinal lymphadenopathy ultimately diagnosed as FL grade 3A, despite an atypical CD5-positive flow phenotype.

This single-patient case report summarizes clinical data, ^18F-FDG PET/CT findings, flow cytometry, histopathology, and management. PET/CT was performed for staging. Lymph node excision provided tissue for histology and immunohistochemistry (IHC). Peripheral blood flow cytometry used a chronic lymphocytic leukemia (CLL) panel. Bone-marrow aspirate/biopsy were attempted for staging.

A 70-year-old man with previously excised cutaneous SCC (disease-free) was evaluated for new left inguinal lymphadenopathy. PET/CT demonstrated a metabolically active left inguinal node (∼17 × 15 mm, SUVmax 12.18) with no other pathologic uptake in the neck, chest, liver, spleen, or adrenals. A posteromedial femoral hypodense nodule (∼20 × 15 mm) and a subcutaneous scapular lesion (∼26 × 20 mm) showed no increased FDG uptake.

Excisional biopsy of the inguinal node revealed non-Hodgkin lymphoma, classic follicular lymphoma, grade 3A (WHO 2016). IHC showed CD20+, BCL6+, BCL2+, CD10+, CD21 positivity in follicular dendritic cells, CD3–, and Ki-67 ∼25%.

Peripheral blood flow cytometry demonstrated B-cell markers with CD5 high (∼71%), CD23 low/negative (∼16%), CD10 low (∼4%), CD43 (∼78%), and mild kappa predominance; findings raised concern for MCL. However, nodal histomorphology with CD10/BCL6 positivity supported FL. Bone-marrow aspirate was suboptimal (particle-poor), and iron score could not be assessed; marrow staging biopsy was planned.

Given grade 3A FL and PET-positive nodal disease, the multidisciplinary tumor board recommended R-CHOP chemoimmunotherapy. Additional work-up (cyclin D1/SOX11 IHC and/or t(11;14) FISH) was advised to definitively exclude MCL due to CD5 expression.

This case highlights two challenges: (1) Dual malignancy in the same patient (prior SCC, now FL) and (2) immunophenotypic discordance between flow cytometry and histology. CD5-positive FL is rare and easily misclassified as MCL; mislabeling could alter therapy (e.g., bendamustine-rituximab vs R-CHOP and consideration of BTK inhibitors in MCL). When flow suggests MCL but node histology/IHC favors FL, tissue-based cyclin D1/SOX11 and t(11;14) are decisive. Suboptimal marrow underscores the need for core biopsy to complete staging. The absence of systemic FDG-avid disease supports localized nodal involvement at presentation.

An older male with previously cured cutaneous SCC developed CD5-positive FL grade 3A presenting as isolated FDG-avid inguinal lymphadenopathy. Despite CD5 expression on flow cytometry, nodal morphology and germinal-center IHC secured an FL diagnosis, and R-CHOP was initiated. This case emphasizes rigorous correlation of flow cytometry with histopathology and the importance of cyclin D1/SOX11/t(11;14) testing when CD5 positivity creates ambiguity.