Pityriasis Lichenoids Chronica as a Paraneoplastic Dermatosis for Primary Splenic Diffuse Large B Cell Lymphoma

Abstracts

Paraneoplastic dermatosis is defined as both benign skin lesions and internal malignancy existing at the same time with parallel clinical courses. Herein, we report a 91-year-old male who presented as pityriasis lichenoids chronica (PLC) concomitantly with a primary splenic diffuse large B cell lymphoma. Surgical removal of the spleen cleared his skin lesions dramatically. However, seven months later, the splenic lymphoma relapsed in concordance with the recurrence of the skin lesions of PLC. To our knowledge, he is the first case that PLC is the leading presentation and paraneoplastic manifestation of primary splenic large B-cell lymphoma.

Introduction

Paraneoplastic dermatoses (PD) occur as non-neoplastic skin lesions developing in the context of an underlying malignancy with a parallel course. The well-known PD are tripe palms, Bazex syndrome, paraneoplastic pemphigus, dermatomyositis, erythema gyratum repens, necrolytic migratory erythema and hypertrichosis lanuginosa acquisa [1]. PDs are associated mostly with solid organ cancers and only a few of them are associated with hematological malignancies. Moreover, PD rarely manifests as pityriasis lichenoids chronica (PLC). The following case highlights PLC as a PD with the development of primary splenic large B-cell lymphoma, an aggressive lymphoma.

Case Report

A 91-year-old male patient had developed multiple scattered asymptomatic and erythematous papules and plaques with centrally adherent micaceous scales on the back, chest and axillae 6 months previously (Fig. 1a, b). He had had coronary artery disease for seventeen years and chronic renal insufficiency for twelve years respectively. No hyphae or fungal elements were identified on potassium hydroxide smear and microscopy examination. Serology tests for syphilis were nonreactive and antinuclear antibodies were negative. Based on the clinical findings, a diagnosis of pityriasis lichenoides chronica (PLC) was considered. He received skin biopsy, which showed focal parakeratosis and spongiotic epidermis with lymphocyte exocytosis, interfaced vacuolated changes and perivascular lymphocyte inflammation in the dermis (Fig. 2a, b). Periodic acid-Schiff stain did not reveal fungal hyphae or spores. These histopathological findings were compatible with PLC. Immunohistochemical exams showed most of the cells in the infiltrate were CD4 positive (Fig. 2c). The skin lesions persisted and even progressed despite treatments with topical antifungal agents, topical corticosteroids, systemic corticosteroids and broad-band ultraviolet B phototherapy three times weekly for half a year at the outpatient clinic.

Fig. 1.

Multiple scattered erythematous papules and plaques with centrally adherent micaceous scales on a back, b a close-up view

Fig. 2.

a Histopathology of skin biopsy showed parakertosis and spongiotic epidermis with lymphocyte exocytosis, interfaced changes and perivascular inflammation in the dermis on low-power field (×100); b High-power view showed interfaced changes and perivascular lymphocyte infiltrate and red blood cell extravasations in the dermis (×400) (H&E)

Because of the protracted course, he underwent further clinical, biochemical and imaging examinations. Examinations for hemogram, complete biochemistry, IgE and tumor markers were all unremarkable. However, abdominal ultrasonography revealed one hypoechoic mass in the spleen (Fig. 3a). Further computed tomography (CT) showed one solitary splenic tumor sized 5.6 cm without lymphadenopathy (Fig. 3b). A laparoscopic splenectomy was then performed. The pathology exam of the splenic tumor demonstrated diffuse large CD20+ lymphoid cells with highly polymorphic nuclei, indicating a diagnosis of diffuse large B-cell lymphoma (Fig. 3c–e). Disease extension workup, including bone marrow aspiration, biopsy and neck-to-pelvic CT, showed negative findings. Hence, primary splenic diffuse B-cell lymphoma was diagnosed. Considering his functional organ reserves at this age, he did not receive further adjuvant chemotherapy. Interestingly, 3 weeks after splenectomy, his skin lesions disappeared dramatically (Fig. 4). He then had a relapse-free period for 7 months until the lymphoma relapsed with several retroperitoneal para-aortic lymphadenopathies when he had poor appetite and generalized weakness. Interestingly, the skin lesions of PLC recurred in concordance with the relapse of the lymphoma. One month later after relapse, hypercalcemia of malignancy developed with persistent left flank pain. Complicated acute pancreatitis occurred thereafter 4 months later with progression of hypercalcemia despite medical managements. Pancreatitis rapidly progressed and was complicated with the development of pneumonia and septic shock, resulting in the patient expiring.

Fig. 3.

a An abdominal ultrasonography revealed a hypoechoic mass in the spleen; b Abdominal computed tomography showed one solitary splenic tumor, size 5.6 cm, without lymphadenopathy; c Microscopically, the splenic mass showed diffuse large lymphoid cells with highly polymorphic nuclei on low-power field (×40) and d high field (×400). e CD20 (pan B-cell marker) was diffusely positive in tumor cells

Fig. 4.

Three weeks after splenectomy, his skin lesions disappeared dramatically

Discussion

In this report, the skin lesions of PLC responded poorly despite several standard treatments in the beginning. Because of the protracted course, the patient received further investigations that identified primary splenic large B-cell lymphoma. He then underwent splenectomy that not only directly removed the tumor burden but also incidentally cleared the refractive skin lesions of PLC. Thus, PLC manifested as a paraneoplastic dermatosis in primary splenic large B-cell lymphoma, a rare lymphoma with aggressive nature.

Paraneoplastic dermatoses can precede, occur concurrently with, or follow the diagnosis of neoplastic disease. Both conditions start approximately at the same time and run a parallel course [2]. The skin lesions not only represent the first clinical sign of underlying malignancy but can also herald the relapse of previous cancer [3]. The well-known PDs are tripe palms, Bazex syndrome, paraneoplastic pemphigus, dermatomyositis, erythema gyratum repens, necrolytic migratory erythema and hypertrichosis lanuginosa acquisa [1]. They are mostly associated with cancers of the solid organs [4] especially those of lungs and gastrointestinal system [5]. Neutrophilic dermatoses (Sweet syndrome, pyoderma gangrenosum), vesiculobullous disorders (paraneoplastic pemphigus) and vasculitis (leukocytoclastic vasculitis, polyarteritis nodosa) are among the few PD that are associated with systemic hematological malignancy [3], including acute or chronic myelogenous leukemia, non-Hodgkin’s lymphoma, and multiple myeloma [4]. The pathophysiology of PD is not fully understood, although aberrant immunological regulations appear to be one of the most important factors that contribute to the pathogenesis of PD [6].

Pityriasis lichenoides chronica is an uncommon inflammatory dermatosis [5, 7, 8]. PLC is usually regarded as a benign disease; nonetheless, it may undergo malignant transformation de novo. For example, transformation of PLC to cutaneous T-cell lymphoma has been reported [5, 9]. However, PLC is rarely presented as paraneoplastic dermatosis. In fact, only two case reports have been described to date. One 37-year-old female had oncocytoma of kidney concurrent with PLC, which was improved after nephrectomy [9]. Another 21-year-old female had PLC that responded well in the beginning, but deteriorated concomitantly with the development of a low-grade lymphoma of lung. The skin lesions improved in accordance with the successful tumor remission by chemotherapy [5]. In our case, PLC presented with the primary splenic lymphoma, a high-grade lymphoma, which has never been reported to date.

Primary spleen lymphoma (PSL) is a rare entity with an incidence of less than 1 % in lymphoma, which is defined firstly by Das Guspa et al.[10] as only involvement of the spleen. Microscopically, diffuse large cell morphology has been reported in 22.4–33.3 % of the cases which have poor outcomes [11–16]. In contrary to systemic diffuse large B-cell lymphoma, localized splenic disease has a relatively favorable clinical course [17]. Furthermore, splenectomy followed by combination chemotherapy results in excellent survival rates [11–16, 18].

In summary, skin manifestations of malignancy are variable. It is important to consider protracted dermatoses as possible paraneoplastic dermatoses as in this patient. Early recognition of underlying disease prompts appropriate therapy and clears the skin lesions earlier [2]. It is worth recognizing refractive pityriasis lichenoides chronica may be the leading sign of an occult neoplasm.