Extravascular papillary endothelial hyperplasia mimicking soft tissue sarcoma in 2 cats: a potential diagnostic pitfall

Abstract

Papillary endothelial hyperplasia (PEH) is a rare soft tissue lesion arising from excessive reactive endothelial cell proliferation described in humans, dogs, and horses. PEH is considered a diagnostic challenge in humans, in which it is frequently misdiagnosed as angiosarcoma. We describe here PEH that developed at injection sites in 2 cats that were initially misdiagnosed as feline injection-site sarcoma by cytology and as subcutaneous angiosarcoma by histopathology. Morphologic features included sharp demarcation from surrounding tissues, and a layered microscopic architecture with an outer fibrous capsule from which emerged fibrovascular stalks covered by a monolayer of factor VIII-related antigen and CD31-positive flat-to-plump endothelial cells. Both lesions had a cystic core containing abundant erythrocytes and fibrin. PEH lesions did not recur in either case. Immunohistochemistry for α-smooth muscle actin and desmin demonstrated that the capsule was devoid of smooth muscle cells, excluding an intravascular origin. PEH in these cats was hypothesized to have developed extravascularly following trauma related to injection. We wish to provide awareness of PEH in domestic cats and of the risk of misdiagnoses leading to overtreatment.

Keywords: angiosarcoma; endothelial cells; feline; feline injection-site sarcoma; hyperplasia; papillary endothelial hyperplasia.

Figures 1–4.

Cytologic, histologic, and immunohistochemical features of feline papillary endothelial hyperplasia (PEH) in 2 cats. Figure 1. Fine-needle aspiration cytology from an intramuscular femoral biceps lesion consistent with PEH in case 1. A moderately cellular sample with a hemorrhagic background. Bland-to-plump, spindle-to-round cells with light-blue, occasionally vacuolated cytoplasm; oval nuclei with granular chromatin are present. Two binucleate cells are visible (arrows). Rare small mature lymphocytes, monocytes, and neutrophils are admixed with the main cell population. May-Grünwald/Giemsa (MGG) stain. Inset: multinucleate giant spindle cell (interpreted as a myofibroblast). MGG stain. Figure 2. Tissue section from a subcutaneous left thoracic mass consistent with PEH in case 2. The lesion is sharply demarcated from surrounding tissues and has a specific layered architecture with an outer capsule (stars) from which emerge fibrovascular stalks. The core of the lesion is composed of abundant blood and fibrin (diamond). H&E. Figure 3. Tissue section from an intramuscular lesion of the femoral biceps in case 1, consistent with PEH. Fibrovascular papillary projections covered by a monolayer of flat-to-plump endothelial cells, infiltrated by small mature lymphocytes and macrophages. H&E. Figure 4. Tissue section from an intramuscular lesion of the femoral biceps in case 1, consistent with PEH. Variable cytoplasmic expression of CD31 by endothelial cells covering fibrovascular stalks. Fibroblasts and inflammatory cells infiltrating the stalks are negative. Anti-CD31 immunoperoxidase stain, diaminobenzidine chromogen, hematoxylin counterstain. Inset: endothelial cells expressing granular cytoplasmic factor VIII–related antigen. In the supporting stroma, accumulation of weak factor VIII–related antigen-positive fibrin is visible. Anti-factor VIII–related antigen immunoperoxidase stain, diaminobenzidine chromogen, hematoxylin counterstain.

Figures 5, 6.

Immunohistochemical expression of alpha–smooth muscle actin (α-SMA) and desmin in a left subcutaneous thoracic mass in a case of feline papillary endothelial hyperplasia (PEH) in case 2. Figure 5. The capsule (stars) is characterized by lack of expression of α-SMA by most of the spindle cells, consistent with reactive fibroblasts. A few spindle cells expressing α-SMA constitute the walls of vessels (arrows) or are scattered cells interpreted as myofibroblasts (short arrow). Fibrovascular stalks contain numerous α-SMA–positive and desmin-negative spindle cells that, according with site and morphology, are consistent with myofibroblasts or pericytes (the latter in the subendothelial lining of the lesion). Anti–α-SMA, immunoperoxidase stain, diaminobenzidine chromogen, hematoxylin counterstain. Inset: note the negativity of endothelial cells covering the papillae and the presence of numerous positive cells consistent with myofibroblasts in the core of the stalks and with pericytes in the subendothelial lining. Anti–α-SMA, immunoperoxidase stain, diaminobenzidine chromogen, hematoxylin counterstain. Figure 6. The spindle cells in the capsule (stars) and papillae are desmin-negative with the exception of smooth muscle cells of the wall of a small vessel (arrow). Anti-desmin, immunoperoxidase stain, diaminobenzidine chromogen, hematoxylin counterstain. Inset: cutaneous surface over the mass with diffuse strong positivity for cutaneous muscle and arrector pili muscles. Anti-desmin, immunoperoxidase stain, diaminobenzidine chromogen, hematoxylin counterstain.