CTCL

Published case study – Primary acral CD8-positive Cutaneous T-Cell Lymphoma with a history spanning over 30 years of relapsing asymptomatic nodules of the left ear

On 10th August 2017, in the Journal of Cutaneous Pathology, Silvia Alberti-Violetti from UOC Dermatologia, Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico, Milan, Italy et al. published a case report of a Caucasian male, 69 years of age, with a history spanning over 30 years of relapsing asymptomatic nodules of the left ear.

Surgery and local radiotherapy were employed to treat the lesions, leading to short-term remissions. He was admitted to the authors’ clinic due to the development of erythematous plaques located on the thighs, buttocks, and feet, as well as a single papule on the right thigh.

After assessment of diagnostic biopsies of different lesions (left ear nodule, a gluteal plaque, and the right thigh papule), a diagnosis of primary acral CD8-positive Cutaneous T-Cell Lymphoma (CTCL) with no systemic involvement was made.

Key Highlights:
  • An identical T-cell clone identified in all skin lesions
  • All lesions showed the same molecular alterations: almost complete deletion of chromosome 13, and losses on 1p33-p22.2, 9p21.3-p21.1, 9q21.11, 9q22.3, 10p15.3-10p13, 11q21-q23.3, 14q31.3, 16q12.1-24.3, and 22q11.1-q12.2
  • Lesions were successfully treated with local radiotherapy on thighs and buttocks, and surgical excision on the ear
  • One year later, patient presented a new large mass on the nose associated with progressive dyspnea and nodules on the hands and legs
  • CT indicated nodular mass involving bony nasal septum and nasal pyramid
  • Biopsy revealed same cytotoxic CD8-positive lymphoid infiltrate
  • Patient treated with six cycles of gemcitabine resulting in stable disease followed by five cycles of bendamustine but skin and nasal lesions progressed
  • Six cycles of multi-chemotherapy with gemcitabine and oxaliplatin led to complete remission of leg lesions, but hand and nasal lesions did not respond
  • At time of last follow-up (2 years after disease had progressed to nasal bone) patient demonstrated stable disease without evidence of dissemination to other sites

The authors state that this case they presented is unique due to the long history of relapsing acral skin lesions without signs of extra-cutaneous spread then being followed by nodules on the nose progressing with a deep mass infiltrating the nasal bone and cartilage. Multiple courses of a range of chemotherapies were administered, but the bone mass has remained unchanged and behaves like an advanced Lymphoma but lacking rapid progression and metastasis which normally accompanies aggressive Lymphomas such as pcAETCLs and PTL-NOS. So far, all other published cases of acral CD8-positive TCL have been characterized as indolent. The authors suggest that the neoplastic cells have a possible central memory T-cell origin, different to pcAETCLs and PTL-NOS, due to being positive for CD62L, TIA1, and BCL6, as well as negative for granzyme B and Blimp-1. The authors concluded by stating that the clinical and histological findings indicate that during the disease course, the neoplastic cells accumulated more and more molecular alterations that contributed to their unusually aggressive behaviour. The exact alterations resulting in the transformation are so far unknown. The group suggest that gathering and comparing long-term follow-up and evaluations of genomic profiles of other patient cases could improve the definition and understanding of this disease entity.

Abstract:

Primary cutaneous acral CD8+ T-cell lymphoma (acral CD8+ TCL) is a new provisional entity characterized by acral skin lesions and an indolent course. We describe an extraordinary case characterized by relapsed nodules with CD8+ cytotoxic infiltrates on the left ear. After 35 years, the skin lesions spread to other acral sites, and a mass with the same histological features as the other skin lesions appeared on the nose. Multiple courses of chemotherapy led to stable disease. Histological examinations carried out at different times showed the gradual transformation of the neoplastic cells with an increased proliferation index. Genomic analysis revealed losses in the regions harbouring the genes involved in cell cycle control. This is the first case of an acral CD8+ TCL with a very long history of indolent nodular lesions progressing to extra-cutaneous sites.

References
  1. Alberti-Violetti S. et al. Primary cutaneous acral CD8 positive T-cell lymphoma with extra-cutaneous involvement: a long-standing case with an unexpected progression. Journal of Cutaneous Pathology. 2017 Aug 10. DOI: 10.1111/cup.13020. [Epub ahead of print].