Clinicopathological Analysis of Uterine Allografts Including Proposed Scoring of Ischemia Reperfusion Injury and T-cell-mediated Rejection-Dallas UtErus Transplant Study: A Pilot Study.

BACKGROUND: Uterus transplantation (UTx) enables pregnancy in infertile women. This study describes the histopathological changes of ischemia reperfusion injury and mostly acute T-cell-mediated rejection (TCMR) in UTx and proposes modification toward a working formulation grading system with associated treatments. METHODS: Protocol and indication biopsies from 11 living and 2 deceased donor UTx recipients were analyzed. Serving as a control were 49 age-matched nontransplanted uteri. All posttransplant histopathological specimens were evaluated in a blinded fashion by 3 pathologists. Response to treatment was assessed by follow-up biopsies. Serial serum donor-specific antibody (DSA) responses were also recorded. RESULTS: Changes attributed to ischemia reperfusion resolved within 2 wk of UTx in most of the patients. For TCMR grading, perivascular inflammation, focal capillary disruption, and interstitial hemorrhage were added to interface inflammation, intercellular edema, stromal inflammation, and epithelial apoptotic bodies. Of the 173 protocol biopsies, 98 were classified as negative for TCMR; 34 as indeterminate-borderline; 35 as mild; 3 as moderate; and 3 as severe, 1 of which occurred in a DSA-positive recipient and also showed microvascular injury. Corticosteroids successfully treated all moderate-to-severe TCMR episodes. Mild TCMR was treated by increasing existing baseline immunosuppression. Indeterminate-borderline episodes were not treated. Neither ischemia-reperfusion injury nor TCMR with DSA adversely affected embryo transfer. CONCLUSIONS: Relying on a modified histopathological grading system, we developed a treatment strategy resulting in resolution of TCMR and successful pregnancies.

Primary rectal monophasic synovial sarcoma.

Synovial sarcoma is a rare malignant mesenchymal neoplasm that often occurs in the extremities. Less than 70 cases of primary synovial sarcoma occurring in the digestive system have been reported. We present a case of a 48-year-old woman with a spindle cell tumor in the rectum that stained positive for AE1/3 (focal), vimentin, CD99, BCL2, EMA (focal), and MiB-1 (15%). Ultimately, the lesion was diagnosed as a primary rectal monophasic synovial sarcoma and confirmed by molecular testing for SYT/SSX1 gene fusion. Analysis of previous publications indicated that patients of advanced age or a large tumor size (≥5 cm) have a higher risk of progressing rapidly to death after diagnosis of synovial sarcoma in the digestive system.

Cutaneous signet-ring cell squamous cell carcinoma.

Cutaneous signet-ring cell squamous cell carcinoma (SRCSCC) is a rare variant, most commonly occurring in the head and neck. We report a case of a 66-year-old transgender woman with an ulcerated growing facial mass measuring 5.6 × 4.0 × 2.0 cm. Histological analysis showed features consistent with SRCSCC. Immunohistochemical analysis showed positive staining for high-molecular-weight cytokeratin, estrogen receptor (1-2+ in 10%), E-cadherin (mostly positive with partial loss), and p40 and negative staining for Ber EP-4, cytokeratin 7, low-molecular-weight cytokeratin, mucicarmine, Alcian blue PAS, HER2, and MUC4. The tumor had invaded the perineurium, lymphovascular spaces, and subcutaneum. Additionally, microsatellite instability testing was negative. This case adds to the limited knowledge of this poorly characterized entity.

Mycobacterial spindle cell pseudotumor in a woman with HIV.

Mycobacterial spindle cell pseudotumor (MSP) is a rare benign entity characterized by tumor-like proliferations of spindle-shaped histiocytes containing acid-fast positive mycobacteria. MSPs tend to occur predominantly in immunocompromised individuals and are concerning for a malignant neoplasm. We report a case of MSP occurring in a woman with human immunodeficiency virus and a tumor-like mass in the abdomen. A subsequent biopsy revealed MSP, which was successfully treated with antimycobacterial therapy.

Myxoma versus myxoid liposarcoma involving the kidneys.

Myxoid lesions of the kidney are rare. We present a case of a 74-year-old man who presented with an 8.5 × 8.0 × 6.0 cm left kidney mass that was grossly confined to the kidney and had a gelatinous cut surface. Histology of the tumor showed bland spindle cells in a myxoid stroma with interspersed thin-walled vessels. The tumor was negative for smooth muscle actin, desmin, CD34 (highlighted vessels), S100, and HMB-45 by immunohistochemistry. There was focal, nonspecific staining of MDM2 and CDK4. The lesion appeared more vascular than would be expected for a classic myxoma and, therefore, fluorescence in situ hybridization was performed for the 12q13 (DDIT3 or CHOP) rearrangement to rule out myxoid liposarcoma and the result was negative for a rearrangement. This case highlights the difficulty of delineating a primary myxoma of the kidney from a well-differentiated myxoid liposarcoma.

An unusual presentation of an uncommon lymphoma, hepatosplenic T-cell lymphoma.

Hepatosplenic T-cell lymphoma (HSTCL) is a rare T-cell lymphoma, primarily characterized by extranodal distribution of the malignant cells with intrasinusoidal infiltration of the liver, spleen, and bone marrow, which is associated with a poor outcome. We describe a unique case of a 47-year-old woman with a clinical presentation of headaches, fevers, elevated liver function tests, and hepatosplenomegaly. A liver biopsy revealed a striking hepatic intrasinusoidal infiltrate of lymphocytes. These were confirmed to be T cells by immunohistochemical stains (CD8+, CD4-, CD3+, CD20-). Molecular studies demonstrated a T-cell gamma receptor gene rearrangement. Clinically, the patient appeared to improve without therapeutic intervention; however, because of the pathologic diagnosis, the patient was initiated on chemotherapy and ultimately underwent a bone marrow transplant.

Von Hippel-Lindau Disease.

Von Hippel-Lindau disease is an autosomal dominant syndrome which occurs secondary to germline mutations in the VHL tumor suppressor gene, located on chromosome 3. Clinically von Hippel-Lindau disease is characterized by an increased risk of developing simple visceral cysts, most commonly in the pancreas and kidneys, in addition to an increased risk of developing neoplasms, often with clear cell features, in a multitude of organ systems. The most common neoplasms are cerebellar and retinal hemangioblastomas, adrenal pheochromocytomas, clear cell renal cell carcinomas, pancreatic neuroendocrine tumors, pancreatic serous cystadenomas, and endolymphatic sac tumors. These lesions most commonly present during adulthood; however, screening and surveillance for the development of these lesions should begin in the pediatric years for patients with von Hippel-Lindau disease. In this review article, the genetics and most common neoplasms of von Hippel-Lindau disease are reviewed, with an eye towards implications for the pediatric patient.