Rheumatoid Arthritis/Methotrexate-associated Primary Cutaneous Diffuse Large B-cell Lymphoma, Leg Type

Matsumoto, Yosuke; Horiike, Shigeo; Maekawa, Saori; Isohisa, Taro; Sakamoto, Natsumi; Chinen, Yoshiaki; Nakayama, Ryuko; Kiyota, Miki; Nagoshi, Hisao; Mizutani, Shinsuke; Shimura, Yuji; Sugitani, Mio; Kobayashi, Tsutomu; Nakai, Noriaki; Kuroda, Junya

doi:10.2169/internalmedicine.53.1735

Cited by 8 publications

(2 citation statements)

References 21 publications

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“…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.…”

Section: Discussionmentioning

confidence: 99%

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

Macklin

Stonard

Matin

et al. 2023

The American Journal of Dermatopathology

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Immunodeficiency-associated lymphoproliferative disorders (IA-LPDs) constitute a diverse range of conditions including posttransplant lymphoproliferative disorders, other iatrogenic IA-LPDs, and lymphoproliferative disorders associated with an underlying primary immune disorder or HIV infection. IA-LPDs are clinically and pathologically heterogeneous, and there is a lack of standardization of diagnostic terminology. They can represent a potential serious diagnostic pitfall because the histological features of clinically indolent proliferations may mimic those of high-grade lymphoma. However, correct identification of these entities is essential given that complete remission may occur upon reversal of the underlying cause of immunosuppression without the need for systemic therapy. IA-LPDs presenting in the skin are rare but well documented. One form of iatrogenic IA-LPD, methotrexate-associated lymphoproliferative disorder (MTX-LPD), can present with cutaneous nodules, plaques, or ulcers. Predominantly, MTX-LPD develops in the context of long-term treatment of autoimmune conditions, such as rheumatoid arthritis, dermatomyositis, and Sjögren syndrome, and may be associated with underlying Epstein–Barr virus (EBV) infection. We present 4 cases of cutaneous EBV-positive B-cell MTX-LPD and describe their clinical and morphological findings. Comparison of our histological findings to the diagnostic criteria for EBV-positive mucocutaneous ulcer (EBVMCU) revealed significant overlap, highlighting the intersection between MTX-LPD and EBVMCU. Withdrawal of methotrexate resulted in healing of all lesions at a mean time of 2 months. In summary, close clinicopathological correlation is vital to identify MTX-LPD presenting as cutaneous EBVMCU given that the initial treatment strategy is that of withdrawal of methotrexate without the need for immediate systemic therapy.

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Section: Discussionmentioning

confidence: 99%

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

Macklin

Stonard

Matin

et al. 2023

The American Journal of Dermatopathology

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“…Methotrexate-associated lymphoproliferative disease is most commonly reported in the rheumatologic literature in patients receiving therapy for rheumatoid arthritis or dermatomyositis. Methotrexate-associated lymphoproliferative disease is rare, and it is associated with EBV in up to 44% of cases . Several variants have been described, but B-cell proliferations are most common .…”

Section: Discussionmentioning

confidence: 99%

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

Malone

Callen

2018

JAMA Dermatol

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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.

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Methotrexate

2015

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Rheumatoid Arthritis/Methotrexate-associated Primary Cutaneous Diffuse Large B-cell Lymphoma, Leg Type

Cited by 8 publications

References 21 publications

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

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

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

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