Zosteriform B-Cell chronic lymphocytic leukemia infiltration
Published Web Locationhttps://doi.org/10.5070/D38ts5q1b3
Zosteriform B-Cell chronic lymphocytic leukemia infiltrationServiço de Dermatologia, Hospital de Santa Maria, Lisbon, Portugal
Joana Antunes MD, David Pacheco MD, Rita Travassos MD, Paulo Filipe MD PhD
Dermatology Online Journal 17 (9): 9
Cutaneous infiltration by leukemic cells is uncommon and may be associated with progression of disease. The authors present the case of a 77-year-old female patient, referred to the dermatology clinic for red, erythematous, pruritic papules, which had suddenly appeared on her left hemithorax, along the C6 dermatome, with a 4-week duration. She had already been medicated with Valacyclovir and Acyclovir for 4 weeks, without clinical improvement. She also had a diagnosis of B-cell chronic lymphocytic leukemia (B-CLL), type 2 diabetes mellitus, and multinodular goiter. Tzanck smear showed no multinucleated giant cells,and PCR testing for Varicella Zoster Virus (VZV) and Herpes Simplex Virus (HSV) on skin biopsy was negative. Histopathology showed a typical B-CLL infiltrate (CD3+, CD20+) and cytogetic analysis was compatible with alterations seen in the bone marrow, confirming the diagnosis of cutaneous infiltration by B-CLL. The patient began chemotherapy with chlorambucil and intravenous human immunoglobulin, which resulted in total regression of the lesions as well as the pruritus. Even though lymphocytic infiltration of Herpes Simplex or Herpes Zoster scars is well documented, cutaneous infiltration with a zosteriform distribution without a previous episode of herpes is very rare. The therapeutic target should be the leukemia itself.
Leukemia cutis (LC) is a nonspecific term used to describe cutaneous infiltration by leukemic cells, either with a myeloid or a lymphoid origin . It may manifest itself as papules, nodules, tumors, plaques, macules, ecchymosis or palpable purpura; skin lesions may be single or multiple [2, 3]. Its incidence is variable, depending upon the type of leukemia. LC is more common in patients with congenital leukemia and in patients with myeloid leukemia . For patients with chronic lymphocytic leukemia (CLL), cutaneous infiltration has been documented in 4 to 20 percent of cases .
When LC appears, it is usually perceived as a sign of an unfavorable outcome, preceding blastic transformation. However, in the case of CLL, a variety of cutaneous infiltrates have been reported, and they do not seem associated with a poorer prognosis [1, 3, 5].
The word zosteriform refers to the distribution of skin lesions, which are unilaterally grouped, along the afferent root of a nerve or a dermatome .
|Figure 1||Figure 2|
The authors describe the case of a 77-year-old female patient, who was observed at the dermatology outpatient clinic, for multiple erythematous pruritic papules, with an average 3 to 5mm in diameter and bright red color. These had suddenly appeared on her left hemithorax, along the C6 dermatome, about 1 month before the consultation (Figure 1). The patient denied ever having had any previous skin lesions on that location. Concerning other health problems, she had a history of B-cell CLL (B-CLL) under clinical monitoring, type-2 diabetes mellitus treated with oral hypoglycemic drugs, and multinodular goited medicated with levothyroxine.
The patient had already been evaluated by her general practioner who had made a diagnosis of Herpes Zoster, and had medicated her with oral valacyclovir 1g tid for 2 weeks. After that period, since the cutaneous lesions showed no improvement, she was prescribed oral acyclovir 800mg 5 times daily for another 2 weeks. After a total of 4 weeks of antiviral therapy, skin lesions were unaltered and the patient was referred to the dermatology clinic.
Laboratory tests included a complete blood count, which showed leukocytosis (77369/μL) and lymphocytosis (70400/μL). Varicella-zoster virus (VZV) serology did not show recent reactivation of the infection (IgM antibodies 3UA/mL – ref.<20; IgG antibodies 4168mUI – ref.<100). A Tzanck smear was performed and no multinuclear giant cells were observed.
Two cutaneous biopsies of individual lesions were also done. Polymerase chain reaction testing for VZV and HSV 1 and 2 was requested. Both tests were negative.
|Figure 3||Figure 4|
Histopathological examination with hematoxylin and eosyn staining showed an infiltrate comprised of small monomorphic lymphocytes, with a perivascular distribution, mainly present in the dermis but also extending down to the hypodermis (Figure 2). Immunohistochemical staining showed the infiltrate to be composed of CD20+ (Figure 3), CD43+ (Figure 4) and, in a smaller proportion, CD5+ cells (Figure 5), which are compatible with transformed B-cells.
Cytogenetic analysis of skin biopsies revealed the same mutations found on the bone marrow aspirate [del(13q14.3) (D13S319) and (D13S25), and t(14q32) IgH].
|Figure 5||Figure 6|
After reaching a diagnosis of cutaneous infiltration by B-CLL with a zosteriform distribution, the patient began chemotherapy with oral chlorambucil 10 mg qid for 5 days and intravenous human immunoglobulin 0.5g/kg/day for 3 days. This treatment resulted in complete regression of the cutaneous lesions; only a few hyperpigmented macules remained (Figure 6).
After a 1-year follow-up, there has been no recurrence of skin lesions and the hematological malignancy remains stable.
B-CLL is a low-grade lymphoproliferative monoclonal hematological condition. It is characterized by the presence of a high number of circulating monoclonal B-cells, which are CD5+. The diagnosis is confirmed by the finding of bone marrow infiltration by the same cells . It is the most common type of leukemia in western countries [1, 7].
These patients often present with cutaneous eruptions, which can be divided into specific and non-specific. Non-specific cutaneous eruptions are more common and include infections, adverse cutaneous drug reactions, immune complex-mediated vasculitis, or neutrophilic dermatoses . Specific cutaneous eruptions result from skin infiltration by neoplastic cells and are named LC .
LC lesions may be single or multiple and frequently are papules, nodules, or plaques, with a red or violaceous color and variable size . Usually, the lesions of LC come about after the patient has been diagnosed with leukemia. However, on fewer ocasions, those lesions may arise simultaneously with the medullary infiltration or may even precede the involvement of bone marrow or peripheral blood. This last event is known as aleukemic LC .
In 1996, Cerroni et al characterized cutaneous lesions specific of B-CLL, from a sample of 42 patients . In their analysis, in addition to the lesions named above, they also observed that LC could appear as vesicles and blisters; they found no preferential location for the appearance of those lesions.
The presence of LC associated with scars of Herpes Simplex or Herpes Zoster is an entity already exhaustively described [5, 9, 11, 12]. Even though the pathophysiological mechanism determining this event is yet to be fully clarified, it is speculated that atypical B-cells may be recruited to the skin responding to an antigenic stimulus. It should therefore be a reactive process, instead of metastatic spread . This hypothesis may also justify the appearance of B-CLL lesions associated with Borrelia burgdorferi infection  or squamous cell carcinoma [8, 15].
However, in the case of the patient here described, skin infiltration by the malignant clone of B-cells did not follow an episode of herpetic infection, as was proven by the medical history, clinical presentation, maintenance of lesions following antiviral treatment, and by diagnostic testing (VZV serology, PCR for VZV and HSV on skin samples). It is therefore a case of leukemic infiltration of skin with a zosteriform pattern.
Cutaneous metastases adopting a zosteriform pattern have been described for T-lymphoma , adenocarcinoma, epidermal carcinoma, melanoma  and, recently, B-CLL . There is still no pathophysiological justification for this kind of presentation, but it is thought that it may result from tumor invasion of the dorsal root ganglion with subsequent peripheral extension, or from lymphoid invasion of intercostal nerves .
The treatment of LC consists mainly of therapies directed towards the primary disease. Traditionally, it was considered that the occurence of LC in patients with B-CLL was a sign of a bad prognosis and was frequently associated with blastic transformation (Richter syndrome or Richter transformation). However, the most recent data does not seem to support this hypothesis; the survival rate should not be affected [5, 14]. Specifically, in cases in which skin lesions appear reactively, such as after herpetic infections, the fact that it may be an immunologic process may be in accordance with the patients’ immunological competence.
Cutaneous infiltration by B-CLL cells is an uncommon situation. The uniqueness of this case report results from lesions being distributed along a without a previous stimulus.
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