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A 46-year-old woman is hospitalized in Riga, Latvia, 1 month after suddenly developing an enlarged chin, which is swollen and tender. She explains that it started quite suddenly, when she was at home watching television and felt that her chin was growing in size. She says her chin was tender to the touch, and had a purple discoloration; she used her cellphone to take pictures of it (Figure 1). Aside from these symptoms, she says she felt fine, with no fever or other problems.

The patient explains that in April 2016 when the symptoms developed, she consulted a local dermatologist and received oral antibacterial treatment with amoxicillin and antihistamines (chloropyramine) and started topical acidum fusidicum; there was no improvement, however.

She notes that 1 month later she was admitted to the dermatology service and received treatment with systemic intravenous glucocorticosteroids (intravenous dexamethasone) for 4 days. This appeared to resolve the symptoms and she was discharged, but the symptoms returned when the glucocorticoids were discontinued.

Medical History

Upon further questioning, the patient recounts that about 3 years previously she developed a non-itchy rash on her chin with raised and flat skin lesions (maculopapular). Her medical history includes a partial thyroidectomy, which she underwent about 3 years earlier in 2013. She has no other medical conditions. She is a non-smoker, and rarely drinks alcohol; her history does not include any information on substance abuse.

August 2016

Clinicians perform a skin biopsy of her chin, which identifies lymphocytoma -- rich skin infiltration with T lymphocytes (CD3+) and focal CD20 positivity. The sample is later reviewed twice by other pathologists.

The initial pathologist's review finds no histological evidence of lymphoproliferative disorder and suggests a possible diagnosis of connective tissue disorder. The second pathologist suggests a diagnosis of pseudolymphomatous folliculitis, noting the same infiltration with CD3+ T lymphocytes.

November 2016

In the absence of a definitive diagnosis, clinicians repeat the skin biopsy. Based on their review of material from this second biopsy, the first pathologist notes inflammatory changes in the dermis with inflammation spreading into the hypodermis and muscle tissue, again showing no sign of lymphoproliferative disorder.

February 2017

The second pathologist reviews the biopsy sample and arrives at a diagnosis of small T lymphocyte lymphoma with monoclonal CD4+ T lymphocyte infiltration. At the same time, the patient develops submandibular lymphadenopathy with a diameter up to 1.8 cm.

March 2017

One month later, clinicians biopsy the patient's lymph nodes and perform a third skin biopsy. The histopathology results note chronic nonspecific lymphadenitis. The skin biopsy report indicates low-grade T-cell lymphoma again, with a morphological and immunohistochemical picture more consistent with primary skin small-to-medium CD4-positive T-cell lymphoma.

A later review of this material by pathologists in Germany at Cologne Institute of Pathology finds nonspecific changes in the lymph node biopsy. These pathologists describe the skin biopsy as follows:

"The skin is covered with regularly matured squamous epithelium; in addition to larger necrotic areas, a mixed inflammatory infiltrate of lymphocytes, plasma cells, and eosinophilic granulocytes is observed mainly in the subcutis. The lymphocytes consist predominantly of CD3+ T cells -- mainly CD4+ T helper cells but also some CD8+ cytotoxic T cells, regularly mixed with CD79a-positive B cells that show focal agglomeration. The cells show no signs of malignancy, with no evidence of activated CD15- and CD30-positive B cells. There is no evidence of T-cell receptor loss detected by immunohistochemistry, nor is monoclonal rearrangement observed in molecular analyzes of the infiltrate. It is classified as pseudolymphoma of the skin."

Treatment History

During different stages of investigation, the patient receives treatment with prednisolone orally with short breaks (30 mg and lower doses), and oral methotrexate for 10 weeks (dose unknown). However, her response to treatment is incomplete and non-persistent. The patient also has several cosmetic procedures performed, including laser therapy, but again without effect.

Diagnosis and Treatment

After confirming a diagnosis of pseudolymphoma and reviewing available sources regarding treatment options, the patient is started on intravenous rituximab monotherapy at 375 mg/m² once a week for 4 weeks. Her condition improves significantly -- skin infiltration decreases, and there is reduced swelling, redness, and cyanosis.

May 2018

Treatment is completed, and at the time of the publication of the , the patient was symptom-free for 16 months (Figure 2).

Discussion

Clinicians reporting this of cutaneous pseudolymphoma note that because it can mimic lymphoma both clinically and histologically, the disorder presents diagnostic as well as treatment challenges. In the absence of clear guidelines for treatment, this patient's case and several previous reports in the literature suggest that rituximab may be used as a treatment option in cases refractory to corticosteroid treatment.

The term "cutaneous pseudolymphoma" describes skin lesions that have some clinical and/or histopathologic resemblance to lymphoma. The few proposed classifications of cutaneous pseudolymphoma are not consensus‐based. Clinicians reporting this case note that categories include B cell pseudolymphomas, T-cell pseudolymphomas, and pseudolymphomas of mixed cellularity. The various historical classifications of multiple lymphoproliferative disorders affecting skin under the term "pseudolymphoma" creates a diagnostic problem and challenges pathologists in proper histological diagnosis, the case authors write.

of suspected cutaneous pseudolymphoma is supported by negative T-cell receptor rearrangement. Pseudolymphoma can present as a solitary nodule or plaque or as disseminated lesions; middle-age women are most commonly affected, often presenting with the localized type.

Pseudolymphoma usually is a benign hyperplastic lymphocyte reaction stimulated by a known or unknown antigen. Its development has been linked with various factors including acupuncture, body piercing, Borrelia burgdorferi infection, insect bites, hirudotherapy, and tattoos.

One recent suggests that the most commonly identified triggers are medications and tattoos. Importantly, presentation of drug-induced pseudolymphoma tends to be insidious.

As a rare disorder, pseudolymphoma presents both diagnostic and treatment challenges. Treatments used include topical, intralesional, and systemic corticosteroids, psoralen and ultraviolet A therapy, and others. The clinician authors note that in the setting of refractory cutaneous pseudolymphoma, a literature search identified at least four articles that described anti-CD20 monoclonal antibody rituximab as an effective treatment option.

Because pseudolymphoma has been known to progress to malignant lymphoma, especially when the antigen stimulus continues, regular follow-up is mandatory.

For this particular case, the patient's quality of life suffered due to her late diagnosis and the need for multiple repeated biopsies. The final diagnosis of cutaneous pseudolymphoma was confirmed only after excluding T-cell receptor rearrangements, thus excluding malignancy.

This was important in differentiating between different lymphoproliferative disorders, the authors note, adding that in addition to assessment of T-cell receptor rearrangement, examination of histopathology and the experience of the pathologist are vital for timely and accurate diagnosis.

Prompt initiation of treatment is especially important if the lesions of cutaneous pseudolymphoma are on the face, since this can have a significant effect on the patient's quality of life. Secondly, the authors reiterate that treatment is needed because pseudolymphoma can progress further into a malignant disorder, like lymphoma.

There have been several reports of successful treatment of cutaneous pseudolymphoma using rituximab. For example, one recent report notes that treatment with intralesional rituximab should be reserved for patients with documented CD20+ lesions. In the absence of treatment guidelines, however, more clinical studies are needed to establish the best therapeutic options.

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