Genevieve M. Crane

Primary CNS lymphoproliferative disease, mycophenolate and calcineurin inhibitor usage

Immunosuppression for solid organ transplantation increases lymphoproliferative disease risk. While central nervous system (CNS) involvement is more rare, we noticed an increase in primary CNS (PCNS) disease. To investigate a potential association with the immunosuppressive regimen we identified all post-transplant lymphoproliferative disease (PTLD) cases diagnosed over a 28-year period at our institution (174 total, 29 PCNS) and all similar cases recorded in a United Network for Organ Sharing-Organ Procurement and Transplant Network (UNOS-OPTN) data file. While no PCNS cases were diagnosed at our institution between 1986 and 1997, they comprised 37% of PTLD cases diagnosed from 2011–2014. PCNS disease was more often associated with renal vs. other organ transplant, Epstein-Barr virus, large B-cell morphology and mycophenolate mofetil (MMF) as compared to PTLD that did not involve the CNS. Calcineurin inhibitors were protective against PCNS disease when given alone or in combination with MMF. A multivariate analysis of a larger UNOS-OPTN dataset confirmed these findings, where both MMF and lack of calcineurin inhibitor usage were independently associated with risk for development of PCNS PTLD. These findings have significant implications for the transplant community, particularly given the introduction of new regimens lacking calcineurin inhibitors. Further investigation into these associations is warranted.

Myocardial calcifications: Pathophysiology, etiologies, differential diagnoses, and imaging findings

Myocardial calcifications are not uncommonly encountered by the cardiac imager and may have a range of imaging appearances, from focal calcific deposits to diffuse myocardial involvement. A number of pathological processes can both cause and result from myocardial calcification; therefore, accurate identification and characterization are important. This pictorial essay will review the mechanisms, etiologies, imaging features, and differential diagnoses of myocardial calcification with imaging examples.

HHV-8-positive and EBV-positive intravascular lymphoma: an unusual presentation of extracavitary primary effusion lymphoma.

Intravascular lymphomas are rare and aggressive hematolymphoid tumors. Here, we describe a human herpesvirus type-8 (HHV-8)/Kaposi sarcoma-associated herpesvirus-positive and Epstein-Barr virus (EBV)-positive intravascular lymphoma. The patient was a 59-year-old human immunodeficiency virus-positive man who presented with diarrhea, abdominal pain, fevers, night sweats, and weight loss. Radiographic studies of the abdomen and pelvis revealed numerous subcentimeter nodules within the subcutaneous fat that lacked connection to the skin. An excisional biopsy demonstrated large atypical cells within vessels in the deep subcutaneous fat, and many of the vessels contained extensive organizing thrombi. The atypical cells lacked strong expression of most B-cell markers but were positive for MUM-1 and showed partial expression of several T-cell markers. An immunohistochemical stain for HHV-8 and an in situ hybridization for EBV were both positive in the neoplastic cells. The disease had a rapidly progressive and fatal course. This lymphoma appears to represent an entirely intravascular form of primary effusion lymphoma and highlights the propensity for HHV-8 and EBV-positive lymphoid neoplasms to show aberrant expression of T-cell markers, illustrates the utility of skin biopsies for the diagnosis of intravascular lymphoma, and suggests that biopsies to evaluate for intravascular lymphoma should be relatively deep and include subcutaneous fat.

Primary effusion lymphoma presenting as a cutaneous intravascular lymphoma

Primary effusion lymphoma (PEL) is a rare and aggressive lymphoma that arises in the context of immunosuppression and is characterized by co‐infection with Epstein–Barr virus (EBV) and human herpesvirus‐8/Kaposi sarcoma‐associated herpesvirus (HHV‐8/KSHV). It was originally described as arising in body cavity effusions, but presentation as a mass lesion (extracavitary PEL) is now recognized. Here, we describe a case of PEL with an initial presentation as an intravascular lymphoma with associated skin lesions. The patient was a 53‐year‐old man with human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS) who presented with fevers, weight loss and skin lesions concerning for Kaposi sarcoma (KS). A skin biopsy revealed no evidence of KS; however, dermal vessels contained large atypical cells that expressed CD31 and plasma cell markers but lacked most B‐ and T‐cell antigens. The atypical cells expressed EBV and HHV‐8. The patient subsequently developed a malignant pleural effusion containing the same neoplastic cell population. The findings in this case highlight the potential for unusual intravascular presentations of PEL in the skin as well as the importance of pursuing microscopic diagnosis of skin lesions in immunosuppressed patients.

Hematolymphoid lesions of the sinonasal tract.

Various hematolymphoid lesions involve the sinonasal tract, including aggressive B, T, and NK-cell neoplasms; myeloid sarcoma; low-grade lymphomas; indolent T-lymphoblastic proliferations; and Rosai-Dorfman disease. Differentiating aggressive lymphomas from non-hematopoietic neoplasms such as poorly differentiated squamous cell carcinoma, olfactory neuroblastoma, or sinonasal undifferentiated carcinoma may pose diagnostic challenges. In addition, the necrosis, vascular damage, and inflammatory infiltrates that are associated with some hematolymphoid disorders can result in misdiagnosis as infectious, autoimmune, or inflammatory conditions. Here, we review hematolymphoid disorders involving the sinonasal tract including their key clinical and histopathologic features.

Tumor-infiltrating macrophages in post-transplant, relapsed classical Hodgkin lymphoma are donor-derived

Tumor-associated inflammatory cells in classical Hodgkin lymphoma (CHL) typically outnumber the neoplastic Hodgkin/Reed-Sternberg (H/RS) cells. The composition of the inflammatory infiltrate, particularly the fraction of macrophages, has been associated with clinical behavior. Emerging work from animal models demonstrates that most tissue macrophages are maintained by a process of self-renewal under physiologic circumstances and certain inflammatory states, but the contribution from circulating monocytes may be increased in some disease states. This raises the question of the source of macrophages involved in human disease, particularly that of CHL. Patients with relapsed CHL following allogeneic bone marrow transplant (BMT) provide a unique opportunity to begin to address this issue. We identified 4 such patients in our archives. Through molecular chimerism and/or XY FISH studies, we demonstrated the DNA content in the post-BMT recurrent CHL was predominantly donor-derived, while the H/RS cells were derived from the patient. Where possible to evaluate, the cellular composition of the inflammatory infiltrate, including the percentage of macrophages, was similar to that of the original tumor. Our findings suggest that the H/RS cells themselves define the inflammatory environment. In addition, our results demonstrate that tumor-associated macrophages in CHL are predominantly derived from circulating monocytes rather than resident tissue macrophages. Given the association between tumor microenvironment and disease progression, a better understanding of macrophage recruitment to CHL may open new strategies for therapeutic intervention.

Langerhans cell histiocytosis of the cervical spine

A 31-year-old male with history of diffuse Langerhans cell histiocytosis (LCH) involving the left mastoid base status post resection and radiation presented with progressive severe rightsided neck pain. Computed tomography and magnetic resonance imaging revealed an osteolytic lesion at C5 (Fig. 1) and because of concern for mechanical instability, the patient underwent a two-stage anterior C5 corpectomy and posterior cervical fusion with instrumentation (Fig. 2). Final pathology of the surgical tissue confirmed LCH (Fig. 3). Postoperatively, the patient’s pain improved, and he continues to undergo chemotherapy for his systemic disease. LCH is a rare disease commonly affecting the bones, and spinal involvement occurs in 6.5–25% of all skeletal cases, with 11% affecting the cervical spine [1]. Patients commonly present with localized neck pain, restricted range of motion, or neurologic deficits [2–4]. Imaging frequently reveals an osteolytic lesion, although osteoblastic lesions can occur [2]. LCH of the spine may be treated conservatively with observation, immobilization, non-steroidal anti-inflammatory drugs and casting, or with radiation, steroids, or chemotherapy—especially in systemic disease or multifocal spine disease [1,2,4,5]. Surgical interventions— that is, curettage with or without bone grafting, internal fixation and fusion, or percutaneous vertebroplasty—may be indicated in cases of severe mechanical instability, deformity, or neurologic deficits caused by compression [1,2].

Epithelial-myoepithelial carcinoma metastasis to the thoracic spine

Epithelial-myoepithelial carcinoma (EMC) is a very rare salivary gland malignancy accounting for less than 1% of salivary gland tumors, and classically arises from the parotid gland in females. Spinal cord compression caused by EMC metastasized from the parotid gland has only been described once in the literature to our knowledge. We report the first case of a patient with parotid EMC spinal metastasis undergoing a gross total resection with instrumented fusion. This case illustrates that an en bloc resection with a planned transgression through the spinal canal may be a reasonable option for EMC metastasized to the spine.

Epidural spinal compression as an initial presentation of Hodgkin lymphoma

Classical Hodgkin lymphoma (CHL) commonly arises in lymph nodes and initial presentation with extranodal disease is rare. We report a patient who presented with progressively worsening back pain, lower extremity weakness and numbness concerning for a myelopathic process of uncertain etiology. MRI revealed an epidural soft tissue mass with cord displacement, for which she underwent resection. Histological analysis of the surgical specimen demonstrated CHL. Further investigation revealed an anterior mediastinal mass, consistent with spread from a more typical location.

Disseminated cat-scratch disease presenting as nausea, diarrhea, and weight loss without fever in a heart transplant recipient

We report the case of an afebrile 59‐year‐old heart transplant recipient presenting with nausea, vomiting, diarrhea, weight loss, and diffuse lymphadenopathy. Lymph node biopsies revealed non‐caseating granulomatous inflammation. Cat‐scratch disease was confirmed by serologic studies, Warthin‐Starry staining, and polymerase chain reaction testing of lymph node tissue. The patients symptoms resolved with 3 months of doxycycline. We review clinical presentations of Bartonella henselae infection and review diagnostic approaches for B. henselae in this patient population.