Gilbert Brodsky

Telepathology diagnosis by means of digital still images: An international validation study

Telepathology affords the means to provide pathological diagnosis and consultation to remote sites. However, before telepathology can become an acceptable medical tool, it will be vital to determine the diagnostic accuracy of this technology. We report the results of a single-blind study of the accuracy of diagnosis performed using computerized still images obtained from a telepathology workstation used in a French telepathology network. Four pathologists, each working alone, reviewed a total of 200 cases of routine surgical pathology (50 cases each), and performed diagnosis based on both computer CD-ROM still images (CD) and conventional glass slides (GS). Concordance between GS and CD diagnosis, as well as accuracy, were determined. Other factors related to performance were also measured, including diagnostic certainty, reasons for uncertainty, and causes of diagnostic error. Overall, there was good agreement between CS and CD diagnosis. There was 87.5% concordance between CS and CD diagnosis, and comparison to consensus (correct) diagnosis showed accuracy of 95.5% and 88.5% for GS and CD diagnosis, respectively. Marked variability in accuracy of CD diagnosis was observed among the four pathologists, and issues related to image selection and/or quality appeared responsible for 60% of the diagnostic errors. The lack of sufficient images and clinical information were frequently cited as reasons for diagnostic uncertainty, as well as feelings of insufficient expertise. It is likely that the opportunity for interaction with the referring pathologist and the use of subspecialty consultants would likely improve the performance of telepathology.

Stage I nonseminomatous germ cell testicular tumor: prediction of metastatic potential by primary histopathology.

A study of 60 patients with clinical stage I nonseminomatous germ cell testicular tumor (NSGCT) was conducted to identify prognostic factors that may predict the likelihood of metastasis. Clinical features and histopathologic features of the primary testicular tumor were examined and analyzed for correlations with the presence of retroperitoneal nodal metastasis documented by surgery (N+) and with development of relapse (R+). Pathologic tumor stage greater than or equal to 2, with tumor extension into the tunica albuginea, rete testis, epididymis, or spermatic cord, was correlated with an increased rate of N+ compared with pathologic tumor stage I (P = .001). Vascular invasion was correlated with a higher rate of N+ (P = .05) and had a similar association with R+ (P = .08). Tumors containing less than 50% teratoma were found to have a higher rate of N+ than tumors with greater than or equal to 50% teratoma (P = .02). Based on the identified prognostic factors, a model for predicting the probability of retroperitoneal nodal metastasis in clinical stage I patients is proposed. The risk factors for nodal metastasis are: pathologic tumor stage greater than or equal to 2, vascular invasion, and less than 50% teratoma. Patients with none of the risk factors are considered at low risk and may be offered orchiectomy alone with surveillance for initial treatment. Patients with all three risk factors are at high risk and should be treated with a retroperitoneal lymph node dissection (RPLND) or possibly chemotherapy. Patients with one or two risk factors are at intermediate risk; it is recommended that they undergo RPLND. This risk model facilitates a rational approach to the management of clinical stage I NSGCT.

The Effects of Various Indwelling Ureteral Catheter Materials on the Normal Canine Ureter

In an attempt to objectively evaluate the biocompatibility of materials commonly used for ureteral stenting, stent-catheters made of four different materials were placed randomly in 31 ureters of 19 mongrel dogs. Animals underwent urography at four weeks and were sacrificed at six weeks. Mild hydronephrosis was noted in eight instances, essentially unrelated to specific material. Silicone, C-flex and polyurethane stents caused a similar, mild degree of ureteral edema, but ureters stented with Silitek demonstrated fairly marked edema. Epithelial ulceration and erosion, often severe, occurred with all polyurethane stents, and rarely with the three other materials. All materials differed statistically from controls, and C-flex caused less reaction overall than polyurethane, indicating differences in biocompatibility of the various materials which may be relevant to their use in patients undergoing long-term ureteral stenting. In practical terms, these suggest that certain materials, notably silicone and C-flex, are more suitable for ureteral stenting than others.

An assessment of grafts in the posterior cricoid lamina

Subglottic stenosis is a recognized complication of prolonged intubation. To date, there is no uniformly successful operative procedure for severe subglottic stenosis, fulfilling the criteria of decannulation and a serviceable voice. The surgical ideals for such a procedure should include the use of autogenous grafting material, avoidance of internal stenting, and limited manipulation of the mucosa. This study was intended to assess the fate of isolated hyoid and thyroid alar grafts interposed in the posterior cricoid lamina. Additionally, anterior/posterior splits with and without anterior grafting were evaluated. Seventeen dogs were used in the determinate animal model. Vocal cord mobility was evaluated by direct laryngoscopy prior to sacrifice. Graphic gross anatomical specimens depict the effects of anterior/posterior splitting on the cricoid cartilage. Clinical correlations are suggested.

Clinical and pathologic features of ductal carcinoma in situ associated with the presence of flat epithelial atypia: an analysis of 543 patients

Flat epithelial atypia is an alteration of mammary terminal duct lobular units that is considered to be a precursor to, or early stage in, the development of some forms of ductal carcinoma in situ. No prior study has systematically evaluated the relationship between various clinico-pathologic features of ductal carcinoma in situ and the presence of coexistent flat epithelial atypia. An understanding of such relationships could provide insight into the connection between flat epithelial atypia and ductal carcinoma in situ. We reviewed slides from 543 ductal carcinoma in situ patients enrolled in a case–control study assessing epidemiologic and pathologic risk factors for local recurrence. We examined the association between the presence of flat epithelial atypia and various clinical factors, pathologic features of the ductal carcinoma in situ, and the presence of coexistent atypical ductal hyperplasia, lobular neoplasia, and non-atypical columnar cell lesions. In univariate analysis, the presence of flat epithelial atypia was significantly related to ductal carcinoma in situ nuclear grade (most common in low grade, least common in high grade; P<0.0001), architectural pattern (most common in micropapillary and cribriform, least common in comedo; P<0.0001), absence of comedo necrosis (P<0.001), absence of stromal desmoplasia (P=0.02) and absence of stromal inflammation (P=0.03). In multivariable analysis, features of ductal carcinoma in situ independently associated with flat epithelial atypia were micropapillary and cribriform patterns and absence of comedo necrosis. Additionally, flat epithelial atypia was significantly associated with the presence of atypical ductal hyperplasia, lobular neoplasia, and columnar cell lesions in both univariate and multivariable analyses. These observations provide support for a precursor–product relationship between flat epithelial atypia and ductal carcinoma in situ lesions that exhibit particular features such as micropapillary and cribriform patterns and absence of comedo necrosis.

Studies of nontraumatic osteonecrosis. The role of core decompression in the treatment of nontraumatic osteonecrosis of the femoral head.

This study reports a five-year experience with core decompression for treatment of nontraumatic osteonecrosis of the femoral head. There were 25 patients (39 hips) with predominantly steroid-associated osteonecrosis followed postoperatively for a minimum of two years. All patients were evaluated functionally, roentgenographically, histologically, and hemodynamically. At latest follow-up examination, two of 12 hips (17%) with Stage I disease, seven of 12 hips (58%) with Stage IIA disease, four of four hips with Stage IIB disease, and nine of 11 hips (82%) with Stage III disease have progressed roentgenographically and/or clinically. A lack of correlation between pressure manometrics, venography, and clinical outcome in this study suggests that mechanisms other than progressive ischemia may be involved. Current indications for core decompression are Ficat Stage 0, I, and IIA (sclerotic predominant) disease.

Nuclear magnetic resonance for the differentiation of benign and malignant breast tissues and axillary lymph nodes.

We have utilized proton T1 (spin-lattice relaxation time) values of Nuclear Magnetic Resonance to study 110 tissue samples obtained from 11 mastectomy specimens. Samples of 1 cm3 from primary tumor sites, nipples, and other breast quadrants, as well as intact lymph nodes were studied and then histologically scored for the presence or absence of carcinoma and, if present, whether it was an isolated microscopic focus (micro). Of 54 samples of breast tissue, 12 contained carcinoma, 5 micro: of 45 lymph nodes, 15 contained metastatic carcinoma, 2 micro; of the 11 nipples, 2 had carcinoma, both micro. For the malignant samples (excluding micro) mean T1 value was 0.47 ± 0.07 sec, (range 0.39–0.79 sec). For the 72 benign samples (excluding nipple) mean T1 value was 0.26 ± 0.03 sec (range 0.14–0.36 sec). The 13 tumor-bearing nodes had a mean T1 value of 0.47 ± 0.03 sec (range 0.40–0.63 sec); mean for the benign nodes was 0.26 ± 0.007 sec (range 0.19–0.35 sec). The differences were highly significant in each case (p < 0.001). For micro examples, T1 values were at malignancy threshold levels or just below, except for nipple tissues, where discrimination was poor. For the 20 other malignant samples, there was no correlation between T1 value and the per cent of sample containing malignancy.

Superficial (early) endocervical adenocarcinoma in situ: a study of 12 cases and comparison to conventional AIS.

Although established histologic criteria for the diagnosis of endocervical adenocarcinoma in situ (AIS) have been published, some lesions are not readily classified or present with more subtle degrees of epithelial atypia. Lesions confined to the surface mucosa may be particularly challenging, possibly because they represent early disease. Twelve cases of superficial AIS (SAIS) confined to the surface mucosa or crypt openings culled from the in-house and consultation practices were examined histologically, immunostained for MIB-1 and p16, and analyzed (when possible) for HPV nucleic acids by DNA-DNA in situ hybridization (INFORM). The mean age was 26.7 years for SAIS versus 37.0 years for 42 consecutive cases of conventional AIS from the same practice (P < 0.001). Seven and five were biopsies and conization specimens, respectively. Five coexisted with CIN, four arose in endocervical papillae, and two arose in endocervical polyps. Nuclear hyperchromasia was conspicuous in 10 and mitoses were present in all; however, apoptosis was rare or absent in four, and six exhibited only mild nuclear atypia. Mib-1 staining exceeded 40% in 5 of 7 cases tested, and all (8 of 8) were strongly positive for p16ink4. Five of five were positive for HPV by ISH with an “integrated” dot-like pattern. SAIS is an early variant of AIS that 1) occurs at a younger mean age, 2) exhibits variable atypia, and 3) arises adjacent to morphologically normal columnar epithelium. Diffuse p16 expression and integrated HPV pattern are identical to that seen in more extensive forms of the disease. Superficial AIS should be suspected in endocervical columnar epithelium with segmental nuclear hyperchromasia with mitotic activity, and confirmed by biomarker staining (p16 and Mib-1) if the pathologist is uncertain of the diagnosis.

Metastasis to the submandibular gland as the initial presentation of small cell ("oat cell") lung carcinoma.

A 45-year-old man had a submandibular mass, which was resected. Histopathologic evaluation and the subsequent course revealed it to be a metastasis from a small cell carcinoma of the lung. This is the first case in which a metastatic lesion in the submandibular gland was the presenting manifestation of an extrasalivary neoplasm, predating discovery of the primary tumor. Metastases to the salivary glands in general and to the submandibular gland in particular are discussed, as is the differential diagnosis with primary salivary gland carcinoma.

Bias in the assessment of family history of melanoma and its association with dysplastic nevi in a case-control study.

Family history of melanoma is an important risk factor for both melanoma and, it is thought, dysplastic nevi. However, assessment of family history of melanoma in epidemiologic investigations has typically been limited to interview of the proband. As part of a case-control study of dysplastic nevi, we attempted to confirm family histories. We disproved about half of the reported family histories of melanoma among first-degree relatives, and confirmed them by medical records in only 17%. Few family histories pertaining to other relatives could be confirmed. We documented the association of melanoma family history with dysplastic nevus risk, and we further documented a substantially greater odds ratio for this association when history was based on confirmation by medical records, compared to confirmation by proband interview only. The bias thus documented must be considered in evaluating the many published epidemiologic studies of melanoma and related disorders. Future research should attempt to confirm family histories of melanoma whenever possible, despite the practical difficulties.