Retrieval of a well-functioning extensor mechanism allograft from a total knee arthroplasty. Clinical and histological findings.

We present the histological findings of an extensor mechanism allograft which was used in a total knee arthroplasty two years after implantation. Analysis of the graft was undertaken at four distinct anatomical levels and it was found to be incorporated into host tissue at each level. A wedge of fibrinoid necrosis, probably related to impingement of the graft on the tibial polyethylene insert, was seen. Impingement may play a role in the injury and necrosis of an allograft and may be one mode of failure in an extensor mechanism allograft.

Gardner-associated fibromas (GAF) in young patients: a distinct fibrous lesion that identifies unsuspected Gardner syndrome and risk for fibromatosis.

Gardner syndrome (GS), caused by mutations in the adenomatous polyposis coli (APC) gene, is characterized by polyposis coli, osteomas, and various soft-tissue tumors. If undetected or untreated, virtually all patients develop colonic carcinoma at a young age. Early detection, while essential, can be difficult because of attenuated phenotypes or spontaneous mutations. We present the clinicopathologic features of 11 identical fibromatous lesions that we have termed Gardner-associated fibroma (GAF), which not only appear to be a part of the spectrum of lesions associated with GS but, in some cases, represent the sentinel event leading to its detection. The GAFs occurred in 11 patients (5 boys and 6 girls; age range, 3 months-14 years), were solitary (n = 7) or multiple (n = 4), and occurred in the superficial and deep soft tissues of the paraspinal region (n = 7), back (n = 3), face (n = 2), scalp (n = 2), chest wall (n = 2), thigh (n = 1), neck (n = 1), and flank (n = 1). Histologically, GAFs resemble nuchal-type fibromas (NFs), consisting of thick, haphazardly arranged collagen bundles between which are found occasional bland fibroblasts, and having margins that frequently engulf surrounding structures including adjacent fat, muscle and nerves. After surgical excision, four patients developed recurrences that were classic desmoid fibromatoses (DFs). In one patient with multiple GAFs, one lesion had the features of GAF and DF in the absence of surgical trauma. A family history of GS or polyposis (n = 6) or DF (n = 1) was known at the time of surgery in seven patients. In three patients, the diagnosis of GAF resulted in the diagnosis of unsuspected APC in older family members, with the detection of an occult colonic adenocarcinoma in one parent. In the family of the remaining patient, no stigmata of GS were present. Genetic analysis of this child was performed to investigate the presence of a spontaneous (new) mutation; however, no abnormalities were detected. The significance of GAF is that it serves as a sentinel event for identifying GS kindreds, including those with a high risk for the development of DF, and it may potentially identify children with spontaneous mutations of the APC gene. Because NFs and GAFs resemble one another, we suggest that a subset of NF occurring in multiple sites, unusual locations, or children may be GAF.

Giant cell tumors of soft tissue: a clinicopathologic study of 18 benign and malignant tumors.

Primary giant cell tumors (GCTs) of soft tissue resembling osseous GCTs are uncommon but distinct entities. Malignant GCTs of soft tissue have been designated giant cell malignant fibrous histiocytomas; however, there is scant data regarding benign GCTs of soft tissue. Eleven benign and seven malignant GCTs of soft tissue were identified from the authors' consultation files and the surgical pathology files of the Vancouver General Hospital and Massachusetts General Hospital. The tumors occurred in adults (eight men, 10 women; age range, 25-89 years; mean age, 54 years) in the extremities (n = 14) and in the trunk, abdomen, and pelvis (n = 4). In each patient the skeleton was normal and there was no history of prior osseous GCT. Tumors ranged in size from 0.8 to 9.0 cm. Eleven occurred in the superficial soft tissue and seven occurred in deep soft tissue. Grossly they were circumscribed and frequently hemorrhagic. Cystic change was present in seven tumors. Nine tumors were partially surrounded by a shell of reactive bone. In all tumors, multinucleated osteoclast-like giant cells were distributed uniformly and evenly among mononuclear cells. The histologically benign GCTs of soft tissue were identical to typical osseous GCTs. The mononuclear cells in these tumors lacked nuclear atypia or pleomorphism, and the mitotic rate within this population was low (mean, three mitoses per 10 high-power fields [HPF]). In the malignant GCTs of soft tissue, the mononuclear cells exhibited anisocytosis, nuclear atypia, pleomorphism, and readily detectable mitoses including atypical forms (mean, 25 mitoses per 10 HPF). None of the benign or malignant tumors exhibited neoplastic bone production. The benign and malignant GCTs of soft tissue demonstrated a similar immunohistochemical staining profile to GCT of bone ( 12 tumors examined), exhibiting strong positive staining for CD68 within multinucleated osteoclastlike cells, and focal staining of mononuclear cells for CD68, Ham 56, and smooth muscle actin. All tumors were treated by surgical resection. Follow-up information is available for 15 patients (range, 0-108 months). No benign tumor has recurred or metastasized. Of the four patients with malignant tumors for whom follow-up information is available, one died of metastatic disease at 13 months and one developed a local recurrence at 84 months but is alive, apparently free of disease after additional excisional surgery. Primary GCTs of soft tissue are distinctive neoplasms that, like osseous GCTs, exhibit a wide clinicopathologic spectrum. These neoplasms should be distinguished from other giant cell-rich soft-tissue tumors with which they may be confused.

Epithelioid angiosarcoma arising in a surgically constructed arteriovenous fistula: a rare complication of chronic immunosuppression in the setting of renal transplantation.

Immunosuppression in the setting of solid organ transplantation is associated with the development of a variety of malignant tumors, most commonly squamous carcinomas and non-Hodgkin's lymphomas. Sarcomas, apart from Kaposi's sarcoma, are relatively infrequent. We recently encountered a 71-year-old man with chronic renal failure, treated by allograft kidney transplantation, who developed a high-grade epithelioid angiosarcoma at the site of a nonfunctioning arteriovenous fistula, previously constructed for hemodialysis. At diagnosis, the patient had numerous satellite nodules of angiosarcoma involving the distal skin, soft tissues, and bones. After a below-elbow amputation, there was a rapid local recurrence at the amputation stump. Currently, the patient is alive with numerous pulmonary metastases, 6 months after amputation. A literature review identified three recently reported identical cases of epithelioid angiosarcoma arising in nonfunctioning arteriovenous fistulae. All three patients had been treated by kidney transplantation for renal failure, suggesting a possible causal association between these events. We performed polymerase chain reaction for human herpes virus 8, the recently recognized herpes virus proposed as a major etiologic agent of Kaposi's sarcoma, and possibly some conventional angiosarcomas, but we failed to identify any viral DNA within the tumor.

Immunohistochemical analysis of bcl-2, bax, mcl-1, and bcl-X expression in ovarian surface epithelial tumors.

Cell survival may be enhanced in tumors by the inhibition of apoptosis, which allows tumor promotors to exert their effects. The bcl-2 related genes have been shown to contribute to either the inhibition or induction of apoptosis in a variety of neoplasms; therefore, it was hypothesized that the expression of these genes might contribute to malignant transformation in ovarian surface epithelial tumors. The expression of bcl-2 family proteins was investigated in 28 ovarian surface epithelial tumors, including serous and mucinous benign, borderline, and malignant tumors by immunohistochemical staining with antibodies to bcl-2, bax, bcl-X, and mcl-1 proteins. Staining intensity was scored on a 1+ to 3+ scale and the benign, borderline, and malignant tumors were compared. Significantly less immunoreactive bcl-2 and bcl-X proteins were present in malignant serous tumors compared to their benign counterparts. No difference was seen in immunostaining for bax or mcl-1 when benign, borderline, or malignant serous tumors were compared. In the mucinous tumors, no differences were seen in immunostaining for any of the bcl-2 family proteins between tumor types. The loss of expression of the antiapoptotic proto-oncogenes bcl-2 or bcl-X in serous carcinomas compared to benign serous tumors, together with previous demonstrations that the presence of bcl-2 in ovarian surface epithelial cancers is a favorable prognostic indicator, suggests that bcl-2 and bcl-X have biological functions in the ovary other than inducing apoptosis, acting instead as tumor suppressor proteins.