Primary cutaneous CD8+ aggressive epidermotropic CTCL

Berti's lymphoma; primary cutaneous aggressive epidermotropic CD8+ T-cell lymphoma; "Berti type" cytotoxic CTCL

Primary cutaneous CD8+ aggressive epidermotropic cytotoxic T-cell lymphoma (Berti's lymphoma) is a rare and aggressive primary cutaneous lymphoma characterised by rapidly evolving generalised eruptions of necrotic, ulcerated plaques, papules and tumours with prominent epidermotropism of CD8-positive cytotoxic T cells. The entity remains a provisional entity / diagnosis of exclusion in WHO-HAEM5 (2022) and the parallel ICC 2022 classifications because of substantial overlap with aggressive CD8+ MF variants, CD8+ peripheral T-cell lymphoma and primary cutaneous γδ T-cell lymphoma; clinicopathological correlation through a cutaneous lymphoma MDT is essential. Unlike the indolent mycosis fungoides, which it superficially resembles morphologically, the disease is rapidly progressive — patients typically present with widespread disease and develop visceral dissemination (lung, CNS, oral mucosa, testis) within months. Distinction from indolent CD8+ disease (mycosis fungoides CD8+ variant; pagetoid reticulosis) is critical and rests on clinical course, distribution and ancillary findings; immunophenotype alone is insufficient. Despite multi-agent chemotherapy and allogeneic stem-cell transplantation, median overall survival remains 22–32 months.

CurrentLast reviewed 26 April 2026

Clinical features

Rapidly developing, generalised, necrotic, ulcerated patches, plaques and tumours.
Predilection for trunk and extremities; oral mucosal involvement common.
Onset over weeks to a few months; established widespread disease at diagnosis.
B symptoms — fever, weight loss, night sweats — common.
Median age 60; both sexes; immune competence does not protect.
Visceral dissemination during the disease course: lung, testis, central nervous system, oral mucosa.
Differential: aggressive transformed mycosis fungoides; primary cutaneous γδ T-cell lymphoma (TCRγδ+); CD8+ MF variant (indolent); pagetoid reticulosis (indolent unilesional); extranodal NK/T-cell lymphoma (CD56+, EBV+).

Histology & immunophenotype

Pleomorphic CD8+ T-cell infiltrate with marked epidermotropism (single-cell and pagetoid pattern), often extending to the spinous and granular layers.
Prominent epidermal necrosis, apoptosis and ulceration.
Angiocentric and angiodestructive growth common.
Phenotype:
- CD3+, CD8+, CD4−, βF1+ (αβ TCR positive — distinguishes from γδ TCL)
- Cytotoxic markers (TIA-1, granzyme B, perforin) strongly positive
- CD45RA+; CD7 frequently lost; CD2 / CD5 often lost
- EBV (EBER) negative
Clonal T-cell receptor β rearrangement.
Differential by histology: indolent CD8+ MF (less epidermotropism, less necrosis, less aggressive clinical course); pagetoid reticulosis (unilesional, indolent); cutaneous γδ TCL (TCRγδ+).

Staging

CT chest/abdomen/pelvis ± PET-CT — visceral dissemination common.
Bone marrow biopsy.
Lumbar puncture if neurological symptoms.
EBV PCR.
HIV testing.
EORTC TNM staging system for cutaneous lymphoma.
Refer to a national cutaneous lymphoma MDT (UK: Guy's, St George's, Manchester).

Management

Multi-agent chemotherapy — CHOP, CHOEP, gemcitabine-based regimens.
Brentuximab vedotin is not a routine option in this entity, which is characteristically CD30-negative or only weakly positive; consider only where CD30 expression has been specifically demonstrated on lesional immunohistochemistry.
Allogeneic haematopoietic stem-cell transplantation in fit patients with chemo-sensitive disease — best chance of long-term remission.
Localised radiotherapy for symptomatic / fungating tumours.
Pralatrexate, romidepsin — relapsed / refractory.
Clinical trial enrolment encouraged.
Palliative care involvement early in unfit patients.

Prognosis

Very poor — median overall survival 22–32 months. 5-year overall survival ~20%. Adverse factors: large tumour burden at presentation, visceral dissemination, B symptoms. Allogeneic transplantation in selected patients can extend survival, but the disease is one of the most aggressive cutaneous lymphomas.

References

Berti E et al. Primary cutaneous CD8-positive epidermotropic cytotoxic T cell lymphomas — a distinct clinicopathological entity with an aggressive clinical behavior. Am J Pathol; 1999.

Willemze R et al. The 2018 update of the WHO-EORTC classification for primary cutaneous lymphomas. Blood; 2019.

WHO Classification of Haematolymphoid Tumours, 5th edition (WHO-HAEM5); 2022. International Consensus Classification of Mature Lymphoid Neoplasms; 2022.