Growth factor modulation of distraction osteogenesis in a segmental defect model.

A model was established in 39 dogs to investigate the growth factor modulation of regenerate bone in distraction osteogenesis. A segment of the diaphysis of the radius was resected unilaterally. An osteotomy was made proximal to the segmental defect to create a transport segment. A monolateral external fixator was applied. After a latency period, the segment was transported across the defect. One week after the transport assembly contacted the distal pin clamp, an ipsilateral osteotomy of the proximal ulna was performed. In 20 dogs, transforming growth factor-beta was injected into the regenerate bone halfway through the transport period. Four dogs were sacrificed before docking, when the regenerate bone was still immature. In specimens harvested halfway through the transport period, evidence was found of intramembranous ossification during distraction. In specimens harvested after the transport assembly contacted the distal pin clamp, evidence was found that the mature regenerate formed by endochondral ossification. Therefore, a combined mechanism of ossification is proposed for this segmental defect model that includes mechanical stimulus for bone differentiation. The one-time administration of transforming growth factor-beta retarded the formation of a stable, united regenerate. It is concluded that transforming growth factor-beta caused an effect opposite to that which was desired.

Overexpression of Her-2 in patients with poorly differentiated carcinoma or poorly differentiated adenocarcinoma of unknown primary site.

PURPOSE: To determine the frequency of Her-2 overexpression in patients with poorly differentiated carcinoma or poorly differentiated adenocarcinoma of unknown primary site. PATIENTS AND METHODS: Tumor specimens from 100 patients with poorly differentiated carcinoma or poorly differentiated adenocarcinoma were stained for the Her-2 protein using the Dako immunohistochemical method. Clinical and pathologic characteristics of patients with and without Her-2 overexpression were compared. RESULTS: Staining for Her-2 overexpression was successful in 94 of 100 patients. Ten (11%) of 94 tumor specimens overexpressed Her-2. Eight of 10 overexpressors had poorly differentiated adenocarcinoma, and all overexpressors had predominant tumor location above the diaphragm, usually in the mediastinum or lungs. CONCLUSION: Her-2 overexpression occurs in a minority of patients with poorly differentiated carcinoma/adenocarcinoma of unknown primary site. Because most overexpressors had poorly differentiated adenocarcinoma, further evaluation of patients with adenocarcinoma of unknown primary site is necessary to determine the frequency of Her-2 overexpression in this common subgroup. Evaluation of the efficacy of trastuzumab in Her-2 overexpressors with carcinoma of unknown primary site is indicated.

Histologic findings of silastic medialization in the canine model.

OBJECTIVES: Examine the long-term histological effects of Silastic medialization using a canine model. STUDY DESIGN: Prospective study evaluating the effects of Silastic medialization in six canine larynges. METHODS: Two subject groups were evaluated. The first group of four dogs underwent recurrent laryngeal section followed by Silastic medialization on the paralyzed side and placement of a smaller implant on the mobile side. Two of the dogs were sacrificed at 9 months and two at 2 years. The second subject group consisted of two additional dogs who underwent Silastic medialization followed by removal of the implants at 7 months and were sacrificed 18 months later. The larynges were then processed, sectioned in the axial plane, and examined microscopically. RESULTS: Histological findings of both the mobile and paralyzed sides showed a thin (< 0.5 mm) fibrous capsule surrounding the implant and minimal inflammatory response. Vocal fold mobility was maintained in all cases in which the recurrent laryngeal nerve was left intact. Capsule formation and inflammatory response were similar in all cases. CONCLUSIONS: Minimal tissue reactivity over a prolonged period of time suggests that long-term results of Silastic medialization remain stable in paralyzed and mobile vocal folds for up to 2 years. Similar tissue response in the subjects in which the Silastic block was removed also suggests that Silastic medialization is a reversible procedure.

Epididymal cribriform hyperplasia. A variant of normal epididymal histology.

We describe a case of orchiectomy for testicular germ cell neoplasm with a peculiar associated cribriform hyperplasia of the epididymis. The process, which we have termed epididymal cribriform hyperplasia (ECH), is tantalizingly akin to patterns of cribriform ductal carcinoma in situ of the female breast and is characterized by complex arcades and cellular bridges spanning dilated epididymal lumina. The cells lining these interconnecting arches have hyperchromatic nuclei, but lack significant atypia or mitotic activity. A limited search of the Vanderbilt University Medical Center (Nashville, Tenn) surgical pathology files produced 30 cases with evaluable epididymis, 15 of which had some degree of ECH. The ECH occurred in a broad age range with a mean of 40 years. No association of ECH with testicular germ cell neoplasia, adenomatous hyperplasia of the rete testis, or parenchymal atrophy could be documented. We conclude that ECH is a seldom recognized variant of normal epididymal histologic appearance that may be present in up to half of epididymides.

Primary lymphoma and Paget's disease of the femur.

Malignant neoplasms associated with Paget's disease of the bone are most commonly metastatic and rarely primary malignant transformations. Sarcomatous transformations, such as osteogenic sarcoma, predominant in Paget's disease. The authors discuss the synchronous and synostotic occurrence of a primary lymphoma of bone in association with Paget's disease. The simultaneous occurrence of isolated primary lymphoma of bone and its phenotype in association with Paget's disease in the femur, which had not been rigorously documented in the previous literature, is reported.

Ductal carcinoma in situ of the breast. Heterogeneity of individual lesions.

BACKGROUND: The increased prevalence of ductal carcinoma in situ (DCIS) has produced a growing awareness of the importance of its diverse patterns. These differences in pattern have become clinically significant as predictive indicators of success for planned local excisions of small DCIS lesions. METHODS: The authors reviewed 100 sequentially collected DCIS cases from a consultation practice. Recognizing the bias of such a series toward exclusion of easily recognizable comedo DCIS, the authors investigated the spectrum of mixed pattern lesions to identify variations and common features in the architectural arrangement of the various histologic patterns. RESULTS: Patterns of atypical ductal hyperplasia (ADH) with specific criteria of recognition were intermixed in 17 cases (11 cribriform, 1 solid, 1 micropapillary, 4 mixed). Thirty-three cases of DCIS consisted of mixed patterns of comedo and noncomedo types. No case of comedo DCIS with associated areas of ADH was identified. In all cases of combined DCIS and ADH, the more advanced patterns of DCIS were present in the central portion of the lesion, with the ADH components arranged peripherally. This tendency for the more severely atypical areas to be located centrally was present throughout the study. CONCLUSIONS: Different patterns of DCIS are frequently present within individual lesions (46 of 100), and the more advanced features of architectural atypia are regularly present centrally. This strongly supports the hypothesis that these lesions develop from a central focus and expand peripherally. Also, those lesions with low-grade DCIS at the periphery may be as amenable to local excision for cure as purely low-grade lesions.

Mesenchymal hamartoma of liver. A regional ischemic lesion of a sequestered lobe.

OBJECTIVE: To evaluate histologic and gross features of mesenchymal hamartoma of liver and similar lesions in relation to determining likely pathogenesis. DESIGN: Case series of patients presenting to a tertiary care hospital over 16 years. PATIENTS: Three children with mesenchymal hamartoma ranging from newborn to 11 months of age and one 12-year-old girl with torsion of an accessory lobe of liver. MAIN OUTCOME MEASURES: Similarity of gross vascular and segmented anomalies as well as apparent consequent histologic features of mesenchymal hamartoma to those of torsion of an accessory lobe of liver indicate that they are pathogenetically related. RESULTS: Dissecting microscopic examination revealed a single vascular supply in one case and remote thrombi in two cases of mesenchymal hamartoma evaluated. The histologic features of mesenchymal hamartoma (hypocellular central zone and hypercellular periphery) were duplicated in the lobe of liver with torsion. CONCLUSIONS: Mesenchymal hamartoma represents a lesion with an anomalous solitary vascular supply that may evolve into its specific pattern with stromal cysts as a result of early ischemic changes.

Tubular adenoma of the main pancreatic duct.

We report a case of tubular adenoma of the duct of Wirsung with focal villous changes. To our knowledge, this is the 13th reported case of this uncommon neoplasm and the first with a primarily tubular histologic pattern. The patient presented with abdominal pain and diarrhea and was found on endoscopic retrograde cholangiopancreaticography to have a mass in the head of the pancreas, which was confirmed by endoscopic ultrasound. Clinical and pathological features of the 12 previously reported cases are reviewed. Intraoperative testing failed to rule out adenocarcinoma which, in addition to difficulties presented by local anatomic relationships of the tumor, supports wide surgical resection as the preferred surgical solution.

The significance of skeletal magnetic resonance imaging after open bone biopsy.

The performance of a bone biopsy results in a dramatically altered magnetic resonance image (MRI) signal in both the biopsied segment and the surrounding bone. An experimental canine model was used to determine the cause and imaging sensitivity of this postbiopsy signal change in the adjacent intraosseous contents. Six dogs were used in the study. Half of the dogs had the cortical window left open, and the other half had a polymethylmethacrylate plug inserted. After hemostatic closure, images were obtained immediately postbiopsy and 6 weeks thereafter. MRI defect length was examined on both T1 and T2 weighted sequences at both time periods. After the final image was taken at 6 weeks, the bone was harvested and examined grossly and histologically for the purpose of making pathoradiographic correlations. The results suggest that magnetic resonance imaging is a sensitive method that accurately reflects the defect caused by bone biopsy and the surrounding hemorrhage. The defect length increased in size over time. The image was slightly smaller than the corresponding histologic response. Insertion of a cortical plug had no predictable effect on defect length, which depended upon the amount of pressurization used during insertion. We conclude that MRI may be useful in the staging of intraosseous primary neoplasms of bone after bone biopsy, especially in the detection of an iatrogenically induced tumor/hemorrhage margin. This may be critical when planning an intraosseous surgical resection in which short, wide margins are anticipated.

Correlation of infecting serovar and local inflammation in genital chlamydial infections.

The relationship between acute inflammation and serovar of Chlamydia trachomatis was evaluated in patients with genital chlamydial infection who attended a sexually transmitted diseases clinic. Polymorphonuclear leukocytes (PMNLS) were enumerated on Gram's-stained smears of endourethral contents in men; cervicitis was scored by visual observation of the endocervix in women. Isolates were serotyped with a monoclonal antibody-based radioimmunoassay. The distribution of serovars in 99 women did not differ in the presence or absence of cervicitis or concurrent gonorrhea. An overall difference (P = .037) was observed when serovar distributions in men with less than or equal to 3 PMNLs (n = 42), greater than or equal to 10 PMNLs (n = 41), and gonococcal urethritis (n = 42) were compared. Follow-up pairwise comparisons revealed that men with less than or equal to 3 PMNLs had fewer isolates of serovars F and G than did men with greater than or equal to 10 PMNLs (P less than .05). No strong overall association was observed between inflammation and serovar.