David M. Weinrach

Laxity in healthy and osteoarthritic knees

OBJECTIVE Although it is a cause of osteoarthritis (OA) in animal models, laxity in human knee OA has been minimally evaluated. Ligaments become more compliant with age; whether this results in clinical laxity is not clear. In theory, laxity may predispose to OA and/or result from OA. Our goals were to examine the correlation of age and sex with knee laxity in control subjects without OA, compare laxity in uninvolved knees of OA patients with that in older control knees, and examine the relationship between specific features of OA and knee laxity. METHODS We assessed varus-valgus and anteroposterior laxity in 25 young control subjects, 24 older control subjects without clinical OA, radiographic OA, or a history of knee injury, and 164 patients with knee OA as determined by the presence of definite osteophytes. A device was designed to assess varus-valgus laxity under a constant varus or valgus load while maintaining a fixed knee flexion angle and thigh and ankle immobilization. Radiographic evaluations utilized protocols addressing position, beam alignment, magnification, and landmark definition; the semiflexed position was used, with fluoroscopic confirmation. RESULTS In the controls, women had greater varus-valgus laxity than did men (3.6 degrees versus 2.7 degrees; 95% confidence interval [95% CI] of difference 0.38, 1.56; P = 0.004), and laxity correlated modestly with age (r = 0.29, P = 0.04). Varus-valgus laxity was greater in the uninvolved knees of OA patients than in older control knees (4.9 degrees versus 3.4 degrees; 95% CI of difference 0.60, 2.24; P = 0.0006). In OA patients, varus-valgus laxity increased as joint space decreased (slope -0.34; 95% CI -0.48, -0.19; P < 0.0001) and was greater in knees with than in knees without bony attrition (5.3 degrees versus 4.5 degrees; 95% CI of difference 0.32, 1.27; P = 0.001). CONCLUSION Greater varus-valgus laxity in the uninvolved knees of OA patients versus older control knees and an age-related increase in varus-valgus laxity support the concept that some portion of the increased laxity of OA may predate disease. Loss of cartilage/bone height is associated with greater varus-valgus laxity. These results raise the possibility that varus-valgus laxity may increase the risk of knee OA and cyclically contribute to progression.

Signet-Ring Cell Change Versus Signet-Ring Cell Carcinoma: A Comparative Analysis

Signet-ring cell change (SCC) is a nonneoplastic condition that morphologically simulates signet-ring cell carcinoma (SRCA). The few case reports on SCC have focused on morphologic characteristics in distinguishing benign from malignant. In biopsy specimens, however, SCC can be easily confused with SRCA, which often demonstrates innocuous cytologic features. The object of this study is twofold: 1) to report 14 additional cases of SCC, comparing their morphologic and phenotypic features with that of SRCA; and 2) to evaluate the incidence of SCC in pseudomembranous colitis. Paraffin sections of biopsy or resection specimens containing focal or extensive SCC and 5 cases of colonic SRCA were stained with hematoxylin and eosin, periodic-acid Schiff stain with and without diastase digestion, and by standard ABC immunoperoxidase procedure using antibodies to E-cadherin, p53, and Ki-67. Both cells in SCC and SRCA were strongly positive for neutral mucins. Cells in SCC were strongly positive for E-cadherin and negative for p53 and Ki-67. In contrast, cells in SRCA were strongly positive for p53, exhibited high proliferation, and demonstrated absent or weak positivity for E-cadherin. Although SCC is not well recognized in pseudomembranous colitis, the incidence is fairly high: 14 of 50 (28%) cases showed variable numbers of signet-ring cells. Extensive SCC, although rare, can occur in different clinical conditions and can be easily mistaken for SRCA. When in doubt, routine immunohistochemical stains such as p53, Ki-67, and E-cadherin can help to differentiate SCC from SRCA.

Carotid Body Tumor: A Case Report

Carotid body tumors are rare neoplasms, which typically present as a slow growing, painless neck mass found along the anterior border of the sternocleidomastoid muscle. These tumors are generally benign but possess aggressive local growth potential. Therefore, definitive treatment requires surgical resection. The authors describe a case of a patient with a carotid body tumor and review the most recent literature on this unusual topic.

Immunohistochemical Expression of Matrix Metalloproteinases 1, 2, 9, and 14 in Dermatofibrosarcoma Protuberans and Common Fibrous Histiocytoma (Dermatofibroma)

CONTEXT Common fibrous histiocytoma (cFH) or dermatofibroma and dermatofibrosarcoma protuberans (DFSP) are 2 spindle cell mesenchymal tumors that are distinguished in part by their microscopic growth patterns and clinically by the greater propensity for DFSP to recur. Matrix metalloproteinases (MMPs) potentially play a role in modulating the growth patterns of cFH and DFSP by remodeling the extracellular matrix. OBJECTIVE To evaluate the immunohistochemical (IHC) expression of MMP-1, MMP-2, MMP-9, and MMP-14 in DFSP and cFH, because (1) MMP-1, MMP-2, MMP-9, and MMP-14 are synthesized by dermal fibroblasts, the major constituent of DFSP and cFH; and (2) platelet-derived growth factor B, which is overexpressed in most examples of DFSP because of t(17;22), activates ets-1, a transcription factor that regulates molecules associated with tumor invasion and metastasis, including MMP-1, MMP-3, and MMP-9. DESIGN Immunohistochemical studies were performed on archived, formalin-fixed, paraffin-embedded tissue of DFSP (n = 48) and cFH (n = 47).Results.-Significant IHC expression (>10% of tumor cells) in cFH included MMP-14 (27 [59%] of 46 tumors positive), MMP-2 (21 [47%] of 45 tumors positive), MMP-9 (9 [20%] of 45 tumors positive), and MMP-1 (6 [13%] of 46 tumors positive). No DFSPs showed significant IHC expression of any of the MMPs evaluated. However, anti- MMP-2 highlighted a rich microvascular element within deep tumor tissue present in 81% of DFSPs with a prominent subcutaneous component. CONCLUSION Our IHC results indicate that MMP-1 and MMP-9 are not up-regulated in DFSP. Convincing expression of MMP-14 in cFH suggests that this MMP may affect the growth pattern of the lesion, perhaps by activating MMP-2 expression in tumor cells. In DFSP, MMP-2 may play a role in tumor angiogenesis.

Soft Tissue Cyst Secondary to Bullet Retention

56-year-old man presented with a painful soft tissue mass in the posterior aspect of the right upper extremity, proximal to the elbow joint. The mass first became noticeable shortly after a gunshot injury to his right elbow region 28 years prior to presentation. Recently, the mass had enlarged to approximately 14 cm. A radiograph of the right elbow revealed a retained bullet within the confines of a well-defined cystic soft tissue lesion, posterior to the distal end of the humerus (Figure 1, arrowheads). Magnetic resonance imaging demonstrated no evidence of communication between the cystic mass and the adjacent joint. Following excision, gross examination revealed a 640-g, 14 3 9 3 6-cm, thick-walled cyst containing 400 mL of turbid brown fluid. The inner surface of the cyst wall was tan-red, smooth, and contained loosely attached necrotic debris. A distorted, silver-gray bullet measuring

Toxoplasmosis in a Bone Marrow Transplant Patient

14-year-old boy underwent an allogenic bone marrow transplant (BMT) 4 months following diagnosis of acute myeloid leukemia. Three weeks after the BMT the patient was intubated secondary to presumed acute respiratory distress syndrome with respiratory failure. The patient’s course was complicated by graft-versus-host disease, recurrent hypotension, hemorrhagic cystitis, and nonoliguric renal failure requiring femoral venous dialysis. The patient improved and was extubated 2 weeks later. The patient’s respiratory status again worsened. Chest radiography showed diffuse infiltrates bilaterally, and the patient required intubation for a second time 5 weeks after the BMT. A bronchoscopy done at the time of the second intubation showed Toxoplasma tachyzoites on cytospins stained with Giemsa (Figure). The patient died 2 days after the bronchoscopy. Autopsy showed disseminated toxoplasmosis. Toxoplasma gondii is a coccidian parasite of cats; humans and other warm-blooded animals serve as intermediate hosts. It belongs to the subphylum Apicomplexa, class Sporozoa, and exists in nature in 3 forms: the oocyst (which releases sporozoites), the tissue cyst (which contains and may release bradyzoites), and the tachyzoite. The tachyzoite form is crescentic and measures 2 to 4 mm wide and 4 to 8 mm long. It requires an intracellular habitat to survive and multiply. Continuous multiplication leads to cell disruption and release of organisms that invade contiguous cells or are phagocytosed and transported to other areas of the body by blood and lymph. Tachyzoites are seen in primary or reactivated infection, and their presence is the hallmark of active infection. 1 Toxoplasmosis is rare following BMT. Because most cases of toxoplasmosis occur in BMT recipients who are seropositive prior to BMT, it is widely believed that toxoplasmosis occurs by reactivation of a latent infection. A few cases have occurred in BMT recipients with negative Toxoplasma antibody titers. In these cases, the infection may have occurred from transmission of infection from

Ferruginous Bodies on Frozen Section

63-year-old man with a history of extensive asbestos exposure and cigarette smoking presented with shortness of breath. The asbestos exposure occurred while the patient was employed as a pipe insulator during the years 1959 to 1973. A computed tomographic scan of the lungs demonstrated bilateral pleural effusions, bilateral pleural plaques, and a 1.3-cm mass in the left lower lung lobe. A left lower lobectomy was performed, and sectioning of the lung demonstrated a 1.3-cm firm, tan-pink mass which was representatively frozen. Microscopically, the frozen section showed adenocarcinoma (Figure 1) associated with ferruginous bodies (Figure 1, arrow). Higher magnification of the ferruginous bodies demonstrated