Thoracic lymphangiomatosis in a child

An 8-year-old boy who presented with a mediastinal mass, pulmonary infiltrates, and disseminated intravascular coagulation was diagnosed with lymphangiomatosis. Despite medical management, he developed multiple organ failure and died. The authors discuss the diagnostic findings, medical management, and pathology and review 52 additional cases of thoracic lymphangiomatosis from the literature. Patients presented with chylothorax (49%), a mass (47%), pulmonary infiltrates (45%), bone lesions (39%), splenic lesions (19%), cervical involvement (15%), disseminated intravascular coagulation (9%), and skin involvement (7%). Children (<16 years) had a worse prognosis than older patients (39% vs. 0% mortality). All patients who died had either parenchymal lung involvement or pleural effusion. Thoracic lymphangiomatosis should be included in the differential diagnosis of a mediastinal mass with pulmonary findings

Bioluminescent Mammalian Cells Grown in Sponge Matrices to Monitor Immune Rejection

The growth and bioluminescence of cells seeded in collagen and gelatin sponge matrices were compared in vitro under different conditions, and immune rejection was quantified and visualized directly in situ based on loss of bioluminescence activity. Mammalian cells expressing a Renilla luciferase complementary deoxyribonucleic acid (cDNA) were used to seed collagen and gelatin sponge matrices soaked in either polylysine or gelatin to determine optimal growth conditions in vitro. The sponges were incubated in tissue culture plates for 3 weeks and received 2, 9, or 15 injections of coelenterazine. Measurements of bioluminescence activity indicated that gelatin sponges soaked in gelatin emitted the highest levels of light emission, multiple injections of coelenterazine did not affect light emission significantly, and light emission from live cells grown in sponges could be measured qualitatively but not quantitatively. Histologic analysis of sponge matrices cultured in vitro showed that cells grew best in gelatin matrices. Visualization of subcutaneously implanted sponges in mice showed accelerated loss of light emission in immunocompetent BALB/c mice compared with immunodeficient BALB/c- scid mice, which was associated with increased cell infiltration. Our results indicate that sponge matrices carrying bioluminescent mammalian cells are a valid model system to study immune rejection in situ

AIDS-Associated BK Virus Nephropathy in Native Kidneys: A Case Report and Review of the Literature

BK virus (BKV) is a small DNA virus, a member of the polyomavirus family, that causes an opportunistic infection in immunocompromised patients, especially kidney transplant patients. This virus establishes a lifelong infection in most of the population, and once it reactivates in an immunocompromised state, leads to BKV nephropathy. This review seeks to assess the correlation between severe immunosuppression, evident by low CD4 cell counts in HIV-positive patients, and the reactivation of BKV, causing nephropathy. A literature review was conducted, extracting, and analyzing case reports of HIV-positive patients showing correlations between their degree of immunosuppression, as evidenced by their CD4 counts, and the degree of BKV infectivity, confirmed by kidney biopsy. A total of 12 cases of BKV nephropathy in HIV-infected patients were reviewed. A common finding was the presence of profound immunosuppression, with most patients having CD4 counts ≤50 cells/ mm3. A substantial number also had comorbid malignancies, with some undergoing chemotherapy, potentially increasing the risk of BKV reactivation. In addition to the HIV status and malignancies, other risk factors for BKV reactivation included older age, male gender, diabetes mellitus, Caucasian race, and ureteral stent placement. BKV nephropathy in HIV patients with native kidneys is closely correlated with severe immunosuppression. Although therapeutic strategies exist for post-transplant patients, aside from the treatment of HIV with highly active anti-retroviral therapy (HAART), which potentially helps with clearing BKV by increasing CD4 count, there is no definitive treatment for a native kidney BKV nephropathy in patients with AIDS. The complexity of the cases and severity of comorbidities indicate the need for further research to develop therapeutic strategies tailored to this population

Use of Electron Microscopy and Other Special Techniques in the Investigation of Suspected Specimen Contamination

Contamination of a biopsy or surgical specimen with spurious tissue is an uncommon but potentially disastrous event. In this regard, the case of a 5-year-old boy referred for treatment of an abdominal tumor is presented. Sections made from paraffin blocks brought by the family showed both neuroblastoma and a spindle cell sarcoma, initially suggesting the possibility of divergent or mixed differentiation. However, the resemblance of the spindle cell component to well-differentiated leiomyosarcoma rather than rhabdomyosarcoma raised the suspicion that a specimen contamination had occurred. Electron microscopy was instrumental in confirming the smooth muscle nature of the sarcomatous component, leading to a fluorescence in situ hybridization study, which established that this component was incompatible with the patient's gender. This case illustrates that even when the light microscopic differential has been compromised by specimen mishandling, electron microscopy can at times provide useful information regarding specimen identity, as well as assist in sorting out the correct diagnosis

Relationship of Post-Transplant Lymphoproliferative Disorders (PTLD) Subtypes and Clinical Outcome in Pediatric Heart Transplant Recipients: A Retrospective Single Institutional Analysis/Experience of 558 Patients

Post-transplant lymphoproliferative disorders (PTLD) are heterogenous lymphoproliferative disorders that develop as a consequence of immunosuppression in transplant recipients. We sought to determine if subtypes of PTLD correlated with different outcomes. We performed a retrospective review of PTLD occurring in pediatric heart transplant recipients. A total of 558 children and infants underwent cardiac transplantation at our institution between 1985 and 2019 and were followed until March 2021. Forty-nine of 558 patients developed PTLD (8.8%). As compared to older children (>one year of age), infant recipients (p = 0.04). Although not reaching statistical significance, patients with a shorter time to PTLD diagnosis showed a trend toward higher rates of M-PTLD or cHL. As expected, the overall survival (OS) of patients with M-PTLD or cHL was significantly lower than patients with non-destructive or polymorphic PTLD

Relationship of Post-Transplant Lymphoproliferative Disorders (PTLD) Subtypes and Clinical Outcome in Pediatric Heart Transplant Recipients: A Retrospective Single Institutional Analysis/Experience of 558 Patients

Post-transplant lymphoproliferative disorders (PTLD) are heterogenous lymphoproliferative disorders that develop as a consequence of immunosuppression in transplant recipients. We sought to determine if subtypes of PTLD correlated with different outcomes. We performed a retrospective review of PTLD occurring in pediatric heart transplant recipients. A total of 558 children and infants underwent cardiac transplantation at our institution between 1985 and 2019 and were followed until March 2021. Forty-nine of 558 patients developed PTLD (8.8%). As compared to older children (&gt;one year of age), infant recipients (p = 0.04). Although not reaching statistical significance, patients with a shorter time to PTLD diagnosis showed a trend toward higher rates of M-PTLD or cHL. As expected, the overall survival (OS) of patients with M-PTLD or cHL was significantly lower than patients with non-destructive or polymorphic PTLD

Complete absence of KSHV/HHV-8 in posttransplant lymphoproliferative disorders an immunohistochemical and molecular study of 52 cases

sosttransplant lymphoproliferative disorders (PTLDs), a heterogeneous group of monoclonal or polyclonal lesions, occur in immunosuppressedpatients after solid organ or bone marrow transplantation. Although most PTLDs are Epstein-Barr virus (EBV)+ and seem to represent EBV-induced proliferations of monoclonal (or less often polyclonal) B, T, or plasma cells, a subset of PTLDs is EBV-. Because Kaposi sarcoma-associated herpesvirus/human herpesvirus 8 (KSHV/HHV-8) has been described in association with the development of hematolymphoid and nonhematolymphoid neoplasms in HIV+ patients, we investigated whether there is an association between KSHV/HHV-8 and PTLDs. Formalin-fixed, paraffin- embedded tissue from 52 confirmed PTLD cases were analyzed immunohistochemically for expression of KSHV/HHV-8 latent nuclear antigen (LNA)-l protein and by polymerase chain reaction-hybridization analysis for the KSHV/HHV-8 genome. The PTLD subtypes included 12 with early lesions (l plasmacytic hyperplasia and 11 infectious mononucleosis-like), 10 polymorphic, 23 monomorphic (5 Burkitt, 14 diffuse large B-cell lymphoma, 1 plasmacytoma, 1 multiple myeloma, and 2 T-cell), 1 Hodgkin lymphoma (HL), 5 HL-like lesions, and 1 unclassified or other. None of the 51 tested specimens showed expression of KSHV/ HHV-8 LNA-1. Furthermore, all 46 specimens tested demonstrated complete absence of the KSHV/HHV-8 genome. Our data clearly indicated that KSHV/HHV-8 is not associated with PTLDs. © American Society for Clinical Pathology

Bioluminescent Mammalian Cells Grown in Sponge Matrices to Monitor Immune Rejection

The growth and bioluminescence of cells seeded in collagen and gelatin sponge matrices were compared in vitro under different conditions, and immune rejection was quantified and visualized directly in situ based on loss of bioluminescence activity. Mammalian cells expressing a Renilla luciferase complementary deoxyribonucleic acid (cDNA) were used to seed collagen and gelatin sponge matrices soaked in either polylysine or gelatin to determine optimal growth conditions in vitro. The sponges were incubated in tissue culture plates for 3 weeks and received 2, 9, or 15 injections of coelenterazine. Measurements of bioluminescence activity indicated that gelatin sponges soaked in gelatin emitted the highest levels of light emission, multiple injections of coelenterazine did not affect light emission significantly, and light emission from live cells grown in sponges could be measured qualitatively but not quantitatively. Histologic analysis of sponge matrices cultured in vitro showed that cells grew best in gelatin matrices. Visualization of subcutaneously implanted sponges in mice showed accelerated loss of light emission in immunocompetent BALB/c mice compared with immunodeficient BALB/c- scid mice, which was associated with increased cell infiltration. Our results indicate that sponge matrices carrying bioluminescent mammalian cells are a valid model system to study immune rejection in situ

Frequent expression of cd99 in anaplastic large cell lymphoma a clinicopathologic and immunohistochemical study of 160 cases

Originally described as a diagnostically useful marker for Ewing sarcoma, CD99 immunoreactivity has also been documented in a variety of other tumors, including hematopoietic neoplasms. By using conventional paraffin immunoperoxidase staining and tissue microarrays, we retrospectively investigated CD99 expression in a series of 160 anaplastic large cell lymphoma (ALCL) cases. Of the 160 cases, 103 (64.4%) were positive for CD99. The distribution of CD99 positivity was similar for nodal (66/103 [64.1%]), extranodal, (21/32 [66%]), and primary cutaneous lesions (16/25 [64%]). CD99 expression was present in 96 (64.4%) of 149 of the common type, 4 (80%) of 5 of the small cell variant, and 3 (50%) of 6 of the lymphohistiocytic variant cases. CD99 expression was slightly more frequent in anaplastic large cell lymphoma kinase (ALK)+ cases compared with ALK- cases (43/54 [80%] vs 44/81 [54%]). With 2 exceptions, ALK+ ALCL was seen only in patients younger than 41 years. We conclude that CD99 is frequently expressed in ALCL, with a slightly increased frequency in the younger age ALK+ cases. Nodal and extranodal ALCL should be considered in the differential diagnosis when a CD99+ neoplasm is encountered. © American Society for Clinical Pathology