Methotrexate-Associated B-Cell Lymphoproliferative Disease in a Patient With Cutaneous T-Cell Lymphoma

Abstract

dorsal midline structures. They are classified as open if the neural tissue is exposed at the skin surface; closed if there is a cutaneous covering. Open spinal dysraphisms include meningoceles and myelomeningoceles, which consist of external protrusions of the meninges alone or both the meninges and the spinal cord, and typically present as translucent midline lesions. 1,2 Closed (occult) spinal dysraphisms are more subtle with overlying, often normal-appearing skin concealing the defect. In up to 76% of cases, however, occult spinal dysraphisms are accompanied by 1 or more paraspinal cutaneous lesions that serve as markers for the underlying malformations. 3 Common manifestations include lipomas, acrochordons, true tails, pseudotails, dimples, dermoid cysts or sinuses, localized hypertrichosis, and vascular abnormalities. These associated lesions most frequently arise in the lumbosacral region but also rarely occur at the cervical or thoracic levels. 4 The concurrence of skin and spinal defects is likely owing to their shared embryologic origin whereby the ectoderm gives rise to both the epithelial and neural ectoderm. 1,2,5 With suspicion for spinal dysraphism, radiologic images should be obtained to rule out neural tissue involvement prior to performing skin biopsies. Magnetic resonance imaging is the first-line choice of diagnostic imaging, but for those with contraindications, ultrasonography provides a cost-effective, albeit less sensitive, alternative. 6 Once identified, spinal dysraphisms warrant further neurological evaluation. If a defect associated with the spinal dysraphism is large enough, it can cause tethered cord syndrome, which presents with a constellation of neurological, orthopedic, and urologic symptoms. [1][2][3] Moreover, when the lesions of the spinal dysraphism provide direct conduits between the central nervous system and the skin surface, recurrent meningitis, often involving Staphylococcus aureus, can occur. 1,2 The present case highlights the importance of obtaining a complete history and cautions against blindly proceeding with a skin biopsy of a suspicious midline lesion without thoroughly reviewing all the possible etiologies of the lesion and carefully considering the potential implications of the biopsy. Clinicians should keep the cutaneous stigmata of spinal dysraphisms on their differential diagnoses of posterior midline or paraspinal lesions. Finally, although spinal dysraphisms most commonly present in neonates and young children, the diagnosis must also be considered in older adults, as this case illustrates.

Methotrexate-induced Primary Cutaneous Diffuse Large B-cell Lymphoma in Patients with Erythrodermic Cutaneous T-cell Lymphoma

“…Four similar cases of PCDLBCL occurring in MTX-treated CTCL have been previously reported in the literature (6)(7)(8)(9). All 7 cases, including ours, were erythrodermic CTCL (4 SS and 3 erythrodermic MF; 5 males/2 females; median age 74 years) and the cutaneous B-cell LPD presented with rapidly evolving cutaneous papules and nodules occurring 2-66 months after MTX introduction (mean 22.8 months) with a close histological pattern of monotonous dermal infiltrate of diffuse large B-cells admixed with features reminiscent of the underlying CTCL in 3/7 cases and positive EBV markers in 6/7 cases (86%).…”

“…Among them, diffuse large B cell lymphoma (DLBCL), either related to Epstein Barr virus (EBV) or not other-wise specified (NOS) and classical Hodgkin disease are the main subtypes, followed by polymorphic/lymphoplasmacytic infiltrates (P/L-I), Hodgkin-like lesions (HLL) and EBV+ mucocutaneous ulcer. MTX-associated LPDs initially presenting with skin lesions have been reported in a minority of cases, and mainly identified as primary cutaneous B-cell lymphoma in single case-reports or small series ( 1 , 4 , 5 ) with only 4 cases in patients with prior CTCL ( 6 – 9 ). We report here on 3 further cases of primary cutaneous B-cell LPD occurring in a setting of CTCL treated with MTX.…”

Skin-Limited, Methotrexate-Associated Epstein–Barr Virus–Positive Mucocutaneous Ulcer—A Mimicker of High-Grade Lymphoma. A Report of 4 Cases and Review of the Literature

“…MTX-LPDs were first described in 1991 12 and, in the setting of rheumatoid arthritis, have been reported to develop after about 11 years of therapy. 13 Reports of cutaneous B-cell MTX-LPD, particularly when lesions are skin-limited, are reasonably rare and they can present with nodules, plaques, or ulcers, 3,14–34 including some cases characterized as EBVMCU. 6,27,35–38 Predominantly, they develop in the context of autoimmune conditions treated with methotrexate, although they have also been reported to arise after treatment of T-cell neoplasms, including mycosis fungoides, Sézary syndrome, and T-cell acute lymphoblastic leukemia.…”

Concurrent Presentation of Mycosis Fungoides and Primary Cutaneous Marginal Zone LPD: Clinicopathological Study of 4 Cases and Literature Review

“…We add 4 cases of primary cutaneous concurrent lymphomas to the 11 previously described cases in the literature. [4][5][6][7][8][9][10][11][12][13][14][15] Altogether, MF was the primary cutaneous T-cell lymphoma (TCL) more frequent (86%), followed by PTCL-NOS (2 cases) and subcutaneous panniculitis-like T-cell lymphoma (1 case). Regarding the associated primary cutaneous B-cell lymphoma (BCL), half of the cases consisted of low-grade B-cell lymphomas, including our 4 cases; 25% were associated to Epstein-Barr virus; 1 case consisted of a methotrexate-associated lymphoproliferative disease, and 2 cases consisted of primary cutaneous diffuse large B-cell lymphoma.…”

“…4 Very few cases of concurrent B-cell and T-cell primary cutaneous lymphomas have been reported in the English literature. 4–15…”