A pacemaker pocket mass has many faces

Abstract

The development of malignant neoplasms over the site of pacemaker implantation is a rare event, with a limited number of published case reports. We report the case of a 78-year-old male who presented with discomfort and pocket mass expansion, reportedly following trauma. Due to initial presumption of a simple hematoma, dissection and drainage were performed without tissue collection for histology. Later presentation with an exophytic ulcerated mass led to biopsy and identification of a lymphoplasmacytic lymphoma. To the best of our knowledge this is the first reported case of a cutaneous lymphoplasmacytic lymphoma presenting as a pacemaker pocket mass, and underlines the importance of systematic pacemaker inspection, of adequate histological characterization and of a high degree of clinical suspicion for the identification malignancy in this context.

<Learning objective: We report the first case of a lymphoplasmacytic lymphoma presenting primarily as a pacemaker pocket mass. Lymphoplasmacytic lymphoma is a rare and indolent subtype of Non-Hodgkin lymphoma that may present with cutaneous manifestations. Due to the extreme rarity of malignant neoplasms presenting as pacemaker pocket masses, a high degree is clinical suspicion is required, and tissue histology plays a key role in the diagnosis.>

Introduction

Despite the growing number of indications for cardiac implantable electronic devices (CIED), with an estimated 1.25 million permanent pacemakers implanted yearly worldwide [1], there is an extremely limited number of case reports of malignant neoplasms developing in pacemaker pockets, including both solid and hematologic malignancies. Whether there is a causal relationship remains a subject of controversy. We present the first case of a lymphoplasmacytic lymphoma presenting as a rapidly growing mass over the site of a pacemaker generator pocket.

Case report

We present the case of a 78-year-old caucasian male with a history of dilated non-ischemic cardiomyopathy and moderately depressed left ventricular ejection fraction (LVEF of 40%), submitted to VDDR pacemaker implantation (BostonScientific INSIGNIA™ I AVT VDR 882) in 2006 due to high-degree atrioventricular block. The patient was later submitted to generator replacement in 2013 due to battery depletion. Other relevant comorbidities included arterial hypertension, dyslipidemia, type 2 diabetes mellitus under oral anti-diabetic drugs, chronic kidney disease and paroxysmal atrial fibrillation, under hypocoagulation with a direct oral anticoagulant. Of note, he was also submitted to a vocal fold carcinoma surgical excision in 2017 and adjuvant radiotherapy in the same year, currently in complete remission.

The patient was admitted to the cardiology department in late 2018 reporting discomfort over the site of the generator pocket following a fall with trauma to this region two weeks prior. He denied a fever, constitutional, respiratory or cardiovascular symptoms, with no other complaints. On presentation, his vital signs and cardiovascular exam were unremarkable and upon inspection pocket expansion was evident, with slight tenderness but no inflammatory signs (Fig. 1). Investigation showed normal blood tests including normal white blood cell count, negative C-reactive protein and procalcitonin, as well as a normal chest X-ray. A set of three blood cultures was drawn from different sights, all of which were negative. CIED interrogation was normal, and a transthoracic echocardiogram was performed showing mid-range LVEF and no signs suggestive of infective endocarditis. Consequently, the patient was admitted and submitted to hematoma drainage the following day, with removal of a significant amount of necrotic material. No pyogenic reaction was apparent. Regrettably, no material was sent for pathological characterization. The patient was prescribed oral flucloxacillin to prevent hematoma infection and was discharged shortly after.

Fig. 1.

Initial presentation of the pacemaker pocket expansion.

Approximately one month later, the patient returned to the emergency department due to development of a large exophytic ulcerating skin lesion, overlying his generator pocket scar (Fig. 2). An urgent dermatology consult was requested, with an initial evaluation suggesting a high probability of malignancy, and so a biopsy of the lesion was performed showing massive infiltration of all dermis by a neoplasia with plasmocytic differentiation, with positivity for CD138 and CD4 and kappa light chain restriction, and with a Ki-67 proliferative index close to 90%, concluding that it could correspond to either a primary cutaneous plasmacytoma or to cutaneous infiltration due to multiple myeloma. After referral for a hematology consult extensive lab tests were performed including complete blood count (CBC) showing normochromic, normocytic anemia with a hemoglobin of 11.1 g/dL and normal white blood cell and platelet counts, negative sedimentation velocity, negative β₂ microglobulin, serum and urinary immunofixation with no monoclonal component and negative serologies for cytomegalovirus, Epstein-Barr and herpes simplex. Allele-specific polymerase chain reaction for MYD88 L265P was also negative. QuantiFERON-TB Gold was positive, despite no knowledge of contact with other patients with tuberculosis. He underwent a thoracic, abdominal and pelvic computed tomography scan that reported a soft tissue maps over the pacemaker generator with 65 by 24 mm, contacting with the pectoralis major muscle in the deep plane, as well as several left axillary lymphadenopathies, the biggest of which with 10 mm. His-bone marrow aspiration and biopsy were compatible with the diagnosis of a lymphoplasmacytic lymphoma with bone marrow infiltration

Fig. 2.

Left infraclavicular lesion overlying pacemaker generator with approximately 10 cm and a central exophytic, vegetating ulcerated area.

Despite initial consideration for possible chemotherapy with bendamustine and rituximab, spontaneous regression of the cutaneous lesion started to occur soon after the initial diagnosis, with a soft tissue ultrasound performed three months later showing no signs of masses overlying the pacemaker pocket. This was also confirmed by a repeat CT and, as such, no therapeutic measure was undertaken in this patient. To this date, at about two year-follow-up, patient remains completely asymptomatic, no recurrence of the cutaneous lesion and only mild anemia.

Due to the diagnosis of likely latent tuberculosis, patient was referred to a tuberculosis clinic after regression of the cutaneous lesion, and was prescribed with isoniazide and pyridoxine for six months.

Discussion

Lymphoplasmacytic lymphomas are rare low-grade B-cell non-Hodgkin lymphomas that occur more frequently in caucasian men, with a median age at diagnosis of 60–70 [2]. Clinical presentation may be either cause by organ involvement or related to IGM paraprotein, but are often nonspecific, with the most common being fatigue caused by the associated-anemia, followed by B-related symptoms such as fever, weight loss and night sweats [2]. Given the indolent nature of the disease, asymptomatic patients are often closely monitored, with chemotherapy being reserved for symptomatic patients [2]. Even though our review of literature identified three other instances of B-cell lymphomas presenting in this way [[3], [4], [5]], to the best of our knowledge, this is the first case report of a cutaneous lymphoplasmacytic lymphoma presenting as a pacemaker mass.

Given the extremely rare nature of cancer developing in pacemaker pockets, the underlying physiopathological mechanisms behind this phenomenon is still unclear, and whether there is a definitive causal nexus or a merely spurious association is still a matter of debate. An epidemiologic study on cancer incidence among pacemaker recipients in Denmark reported only a very slight excess of overall cancer, mostly due to an increase in multiple myeloma among men and kidney cancer in women [6]. Proposed mechanisms behind this association include a potential adverse effect of titanium, as well as inflammatory oncotaxis related to chronic irritation caused by the pacemaker itself, with resulting inflammation in the surrounding tissue [3, 7]. An in vivo study of titanium dioxide particles in rats has demonstrated effects that may contribute to the susceptibility of tumor growth, namely reduced activity of macrophages and natural killer cells and altered proliferation of B and T-lymphocytes [8]. Electromagnetic fields have also been proposed as potential causes for cancer induction, but animal experiments have not supported this idea [9]. Consequently, despite the theoretical rationale that metallic implants could predispose to the proliferation of malignant cells, this requires further investigation and validation. Furthermore, previous exposure to therapeutic radiation may also contribute towards an increased risk for certain malignancies, including non-Hodgkin lymphoma.

In this instance, the temporal coincidence of trauma to the generator site, especially in the setting of hypocoagulation, made the initial diagnosis of a simple hematoma the most likely option, seeing as this one of the most common complications following CIED implantation [10]. However, despite the rare nature of this clinical entity, and even if the location of this neoplasm is entirely coincidental, this case reinforces the importance of careful pacemaker pocket inspection during routine visits, as well as the need for adequate tissue histology for assessment of potential differential diagnosis. Additionally, definite diagnosis required the input and collaboration of different specialties, reinforcing that a high degree of clinical suspicion for is required of the cardiologist in order to prompt a timely diagnosis.

Declaration of Competing Interest

The authors declare that there is no conflict of interest to disclose.