Zosteriform Primary Cutaneous Marginal Zone Lymphoma—A Case Report

ABSTRACT

We report a case of zosteriform PCMZL presenting in a T3–T4 dermatomal distribution not previously described in the literature. Although the varicella zoster virus was not detected in this case, late diagnosis of the acute eruption of zoster or even preceding zoster ‘sine herpete’ cannot be excluded as antigenic triggers.

1. Introduction

We present the first reported case of zosteriform primary cutaneous marginal zone lymphoma (PCMZL).

Primary cutaneous B‐cell lymphomas are extranodal non‐Hodgkin B‐cell lymphomas that arise in the skin in the absence of systemic involvement after staging is performed. The WHO Classification of Tumours (5th edition) includes indolent forms, such as primary cutaneous follicle centre lymphoma, PCMZL and some more aggressive forms, such as primary cutaneous diffuse large B‐cell lymphoma, leg type [1].

The 2022 International Consensus Classification of Mature Lymphoid Neoplasms proposes to rename PCMZL as primary cutaneous marginal zone lymphoproliferative disorder (PCMZLPD) due to its invariably benign clinical course with disease‐specific survival of almost 100% [2].

PCMZL typically presents with solitary or multiple papules, plaques and nodules on the trunk and arms [3]. Several clinicopathological variants of PCMZL are recognised, including conventional, lymphoplasmacytic and plasmacytic, as well as cutaneous amyloidoma [3]. Cutaneous relapses are common [2], but dissemination to extracutaneous sites is rarely observed.

We report a novel presentation of PCMZL in a zosteriform distribution, in a patient with possible low‐volume nodal disease, and explore the impact of varicella zoster virus in the pathogenesis.

2. Case Presentation

A 75‐year‐old woman presented with a 2‐year history of an asymptomatic plaque on the left upper back. The past medical history included left breast cancer (diagnosed at 70 years old, treated with lumpectomy and lymph node excision, adjuvant radiotherapy and adjuvant endocrine therapy (anastrozole)), osteoporosis, chronic obstructive pulmonary disease and hypertension.

She had seen her general practitioner 1 year prior, who prescribed oral valaciclovir for presumed herpes zoster. Despite completion of the course of antiviral therapy, there was no clinical benefit, and swabs for varicella zoster virus PCR proved negative. Varicella serology (IgM and IgG) was not performed. The patient had no history of herpes zoster previously and reported no pain or paraesthesia prior to lesion onset.

The plaque gradually enlarged and became pruritic, and a trial of potent topical corticosteroids (betamethasone dipropionate 0.05% ointment, methylprednisolone aceponate 0.1% ointment and mometasone furoate 0.1% ointment) also failed. The patient was systemically well throughout this period without weight loss, night sweats or fatigue.

On examination, there were erythematous, infiltrated papules and nodules on the left upper back, confined to the distribution of the T3–T4 dermatomes (Figure 1). There was no evidence of hepatosplenomegaly or lymphadenopathy.

FIGURE 1.

Erythematous, indurated papules and nodules on the left upper back, confined to the T3–T4 dermatomes.

An incisional biopsy was sent for histology and flow cytometry. There was evidence of a B‐cell dominant lymphoid proliferation with plasmacytic differentiation and light chain restriction consistent with PCMZL (Figures 2 and 3).

FIGURE 2.

Nodular and diffuse infiltrate (A). Occasional reactive germinal centres with an expanded ‘dark’ mantle zone (B). Numerous plasma cells and small lymphocytes contribute to interfollicular or marginal zone expansion (C) (Haematoxylin and Eosin).

FIGURE 3.

Immunohistochemistry performed on the abnormal lymphoid infiltrate population showed kappa light chain restriction (A) and no evidence of lambda light chain staining (B).

Immunohistochemistry performed on the abnormal lymphoid infiltrate population showed positive CD20, PAX5 (B‐cells), CD79a (plasma cells and B‐cells) and CD138+ marginal zone plasma cells with kappa light chain restriction (Figure 3A), with no evidence of lambda light chain staining (Figure 3B). CD10 and BCL6 were positive in atretic germinal cells, which were negative for BCL2 and showed a higher ki67 proliferative index consistent with residual, reactive germinal centres.

Flow cytometry demonstrated no evidence of an abnormal lymphocyte population. The lymphocyte region consisted of T cells (28%; CD4:CD8 = 2), polyclonal B cells (52%; Kappa: Lambda = 1.3) and NK cells (5%). However, false‐negative results are not uncommon due to the intricacies in preparing a single‐cell suspension of PCMZL [4], with a subsequent reliance on immunohistochemistry to determine the immunophenotype.

Blood tests performed demonstrated a white cell count of 9.9 × 10⁹/L, neutrophil count of 5.4 × 10⁹/L, haemoglobin of 134 g/L and platelet count of 305 × 10⁹/L. Blood film showed no significant morphological abnormality. Renal function was normal, and lactate dehydrogenase was not elevated (155 U/L). Immunoglobulin levels (A, G, M) and serum‐free light chains were unremarkable, and no paraprotein was detected. Serum protein electrophoresis demonstrated an oligoclonal pattern present. Urine protein electrophoresis was not performed. Antibodies to Borrelia burgdorferi were not performed due to a lack of contact with endemic regions. Hepatitis serology was not performed in this case.

The case was thought not to represent cutaneous plasmacytoma due to the lack of monotypic light chain expression. Similarly, cutaneous involvement of plasma cell dyscrasia or myeloma was deemed less likely as serum‐free light chains were normal and there was a lack of evidence of systemic features of plasma cell proliferation, including hypercalcaemia, renal dysfunction or anaemia. Plasmacytic lymphoma was also thought to be less likely, given the patient's immunoglobulin studies were normal, with no evidence of pancytopenia.

CT chest, abdomen and pelvis demonstrated no lymphadenopathy. PET scan demonstrated low‐volume uptake at the left posterior thoracic wall and mild to moderately avid lymph nodes above and below the diaphragm.

The patient was subsequently referred to haematology and radiation oncology. Her case was discussed at a multidisciplinary team meeting (haematology, pathology, radiology and radiation oncology). After reviewing her skin biopsy and PET scan, the assessment was made that she had cutaneous marginal zone lymphoma with asymptomatic low‐volume nodal involvement above and below the diaphragm. Given that the zosteriform cutaneous presentation was the patient's only symptomatic site of disease, radiotherapy was recommended (24Gy over 12 fractions) with repeat imaging 6 months after treatment to assess her presumed nodal disease with consideration of systemic approaches if needed. Skeletal imaging, bone marrow biopsy and lymph node biopsy of PET‐avid lesions were not performed.

After completion of radiotherapy over 4 weeks, the patient self‐reported a measurable difference in the plaque, which was no longer as pruritic or raised.

3. Discussion

Wolf's isotopic response refers to the appearance of a distinct skin disease at the site of a previous dermatosis, with an interval ranging from days to years [5]. Herpes zoster is the most common primary disease [5], and a plethora of dermatoses have been described within areas of resolved zoster, including granuloma annulare, lymphomas, pseudolymphomas, sarcoid granulomas, tuberculoid granulomas, granuloma vasculitis, squamous cell carcinoma, angiosarcoma, Kaposi sarcoma, cutaneous T‐cell lymphoma and B‐cell lymphoma [6]. Zosteriform cutaneous metastases have also been reported in various visceral, haematologic and cutaneous malignancies [7]. The isotopic response may result from persistent antigenic stimulation in the setting of Type III or IV hypersensitivity to viral antigens, which is distinct from the Koebner phenomenon [8].

While varicella zoster virus was not detected in this case, late diagnosis of the acute eruption of zoster or even preceding zoster ‘sine herpete’ cannot be excluded as antigenic triggers for lymphomagenesis. Mucosa‐associated lymphoid tissue (MALT) lymphomas are extranodal marginal zone lymphomas that are known to result from chronic antigenic stimulation by organisms such as Helicobacter pylori (gastric), Chlamydia psittaci (conjunctival) and Borrelia burgdorferi (cutaneous) [9], and PCMZL may share a similar pathomechanism. Similarly, hepatitis C infection is associated with the development of indolent and aggressive B‐cell lymphoma; however, the causal association between hepatitis C infection and B‐cell lymphoma remains ill‐defined [9]. An alternative hypothesis is that preceding infection alters the local immunological milieu, creating a locus minoris resistentiae for proliferation of a future aberrant B‐cell clone [7].

It remains uncertain whether the initial rash reviewed by the general practitioner was true zoster, as we did not review the rash directly. Whether the rash was due to zoster or lymphoma remains to be elucidated.

There are isolated case reports of primary cutaneous follicle centre lymphoma and diffuse large B‐cell lymphoma in a dermatomal distribution, and involvement of herpes zoster in these cases was also speculated [10]. Similarly, atypical cases of zosteriform mycosis fungoides in areas of prior herpes zoster, which have responded to valaciclovir, have been described [11]. In our case, it may have been worthwhile to trial a further course of valaciclovir and to consider it in other zosteriform distribution eruptions in future.

As the first reported case of zosteriform PCMZL, our case report adds to existing knowledge of the disease and encourages clinicians to consider it as a potential differential diagnosis for zosteriform lesions.

4. Conclusion

In conclusion, we present the first reported case of zosteriform PCMZL.

Consent

The patient provided informed consent for the publication of this manuscript.

Conflicts of Interest

The authors declare no conflicts of interest.

Teh N., Byth L., Loh V., Krishnaswamy M., and Zagarella S., “Zosteriform Primary Cutaneous Marginal Zone Lymphoma—A Case Report,” Australasian Journal of Dermatology 66, no. 6 (2025): e365–e368, 10.1111/ajd.14565.

Data Availability Statement

The authors have nothing to report.