Paul A. Kay

Invasive micropapillary salivary duct carcinoma : a distinct histologic variant with biologic significance

An invasive micropapillary component has been described in tumors of several organs and is nearly always associated with aggressive biologic behavior. We present 14 cases of salivary duct carcinoma (SDC) with an invasive micropapillary component (invasive micropapillary SDC) and compare the clinicopathologic findings of these cases with those of cases of conventional SDC. The mean age of the 14 patients (10 men, 4 women) was 65.8 years (range, 26–80 years). The mean size of the tumors was 2.4 cm (range, 1.3–5 cm). The parotid gland was involved in 12 patients and the submandibular gland in 2. Histologically, all tumors had an invasive micropapillary architecture admixed with features typical for SDC. Invasive micropapillary carcinoma was characterized by morula-like small cell clusters without fibrovascular cores, surrounded by a clear space. Tumor cells exhibited moderate- to high-grade nuclear features, conspicuous nucleoli, and eosinophilic cytoplasm. This component was distributed diffusely in 9 tumors and focally in 5. Angiolymphatic and perineural invasion was seen in all tumors. A residual pleomorphic adenoma was detected in four tumors. Of the 12 tumors examined, all were diffusely positive for cytokeratin 7 and epithelial membrane antigen (with a distinctive “inside-out” pattern) but negative for cytokeratin 20. Tumors were frequently immunoreactive for BRST-2 (gross cystic disease fluid protein-15) and androgen receptor protein. Aberrant expression of HER-2/neu or p53 was detected in seven tumors each. The mean Ki-67 labeling index was 33.1% (range, 6.3%–61.6%). All 14 patients with invasive micropapillary SDC had cervical or periglandular lymph node metastasis, and this value was significantly higher than for conventional SDCs. Local recurrence developed in 4 patients and distant metastatic disease in 9. Clinical follow-up (mean, 25.5 months) was available for 13 patients: 9 died of disease within 24 months after the diagnosis (mean, 17.6 months), 1 was alive with metastatic disease at 19 months, and 3 were free of disease. Overall survival of these patients with invasive micropapillary SDC was significantly shorter than that of patients with conventional SDC (n = 49) in our series (P = 0.031). Our results suggest that invasive micropapillary SDC is a distinct, aggressive variant of SDC, with a propensity for extensive lymph node metastasis and rapid disease progression.

Dedifferentiated Adenoid Cystic Carcinoma: A Clinicopathologic Study of 6 Cases

Dedifferentiated adenoid cystic carcinomas are a recently defined, rare variant of adenoid cystic carcinomas characterized histologically by two components: conventional low-grade adenoid cystic carcinoma and high-grade “dedifferentiated” carcinoma. We examined six cases and analyzed their clinicopathologic profiles, including immunohistochemical features and p53 gene alterations. The 6 patients (3 men and 3 women) had a mean age of 46.8 years (range, 34–70 y). The mean size of the tumors was 3.5 cm (range, 1.7–6 cm). The submandibular gland, maxillary sinus, and nasal cavity were involved in 2 cases each. Postoperatively, 5 patients had local recurrence and 5 developed metastatic disease. Five patients died of disease at a mean of 33.7 months after diagnosis (range, 6–69 mo), and one other was alive with disease at 60 months. Histologically, the conventional low-grade adenoid cystic carcinoma component of the tumors consisted of a mixture of cribriform and tubular patterns with scant solid areas. The high-grade dedifferentiated carcinoma component was either a poorly differentiated adenocarcinoma (4 cases) or undifferentiated carcinoma (2 cases). Three tumors were studied immunohistochemically. Myoepithelial markers were expressed in low-grade adenoid cystic carcinoma but not in the dedifferentiated component. In 2 cases, diffusely positive p53 immunoreactivity together with HER-2/neu overexpression was restricted to the dedifferentiated component. Loss of pRb expression was demonstrated only in the dedifferentiated component of the 1 other case. The Ki-67–labeling index was higher in the dedifferentiated component than in the low-grade adenoid cystic carcinoma component. Furthermore, molecular analysis of 2 cases demonstrated the loss of heterozygosity at p53 microsatellite loci, accompanied by p53 gene point mutation, only in the dedifferentiated carcinoma component of 1 case, which was positive for p53 immunostaining. These results indicate that dedifferentiated adenoid cystic carcinoma is a highly aggressive tumor. Because of frequent recurrence and metastasis, the clinical course is short, similar to that of adenoid cystic carcinomas with a predominant solid growth pattern. Limited evidence suggests that p53 abnormalities in combination with HER-2/neu overexpression or loss of pRb expression may have a role in dedifferentiation of adenoid cystic carcinoma.

PUBOPERINEALES: MUSCULAR BOUNDARIES OF THE MALE UROGENITAL HIATUS IN 3D FROM MAGNETIC RESONANCE IMAGING

PURPOSE The aims of this report are 1) to extend our previous two-dimensional magnetic resonance imaging study to create a three-dimensional image of the pelvic floor, including the puboperinealis, the most anteromedial component of the levator ani; 2) to clarify the historical controversy about this particular component of the levator ani; and 3) to present clinical implications of this muscle with respect to urinary continence and radical prostatectomy. MATERIALS AND METHODS We reused the axial magnetic resonance imaging series from 1 of 15 men in a previous series. Analyze AVWTM allowed creation of three-dimensional images. Further, a movie clip of all three-dimensional images was developed and placed at the manuscript-dedicated Web site: http://www.mayo. edu/ppmovie/pp.html. RESULTS Our three-dimensional images show how the puboperinealis portion of the levator ani flanks the urethra as it courses from the pubis to its insertion in the perineal body. CONCLUSIONS The puboperinealis corresponds to muscles previously designated as the levator prostatae, Wilsons muscle, pubourethralis, and levator urethrae, among others. The images suggest that the puboperinealis is the muscle most responsible for the quick stop phenomenon of urination in the male. Our study supports the suggestion that weakening of the puboperinealis by transection, traction injury, or denervation may affect urinary continence after radical prostatectomy.

Dedifferentiation in low-grade mucoepidermoid carcinoma of the parotid gland

Mucoepidermoid carcinoma (MEC), a common malignant salivary gland neoplasm, is generally divided into low-, intermediate-, and high-grade types according to the histologic features. To our knowledge, the present report describes the first case of dedifferentiation occurring in a low-grade MEC. A 55-year-old man presented with a biphasic neoplasm of the right parotid gland composed of low-grade MEC and dedifferentiated high-grade anaplastic undifferentiated carcinoma. Immunohistochemically, carcinoembryonic antigen expression was restricted to the low-grade MEC portion. The Ki-67-labeling index was higher in the dedifferentiated component than in the low-grade component. On image cytometric analysis, the low-grade MEC was diploid, whereas the dedifferentiated carcinoma was aneuploid. Although the patient was alive 10 years after the initial diagnosis, the tumor has recurred twice, at 3 months and 7 months after the initial resection. It is important to recognize that dedifferentiation can occur in a low-grade MEC, similar to other low-grade salivary gland carcinomas.

Prostate cancer microvessels: a novel method for three-dimensional reconstruction and analysis

Studies of prostate cancer microvessels to date have relied on routine two‐dimensional images from histologic tissue sections, and there have been no previous reports of three‐dimensional (3D) reconstruction and analysis of prostatic microvessels in benign or malignant specimens. Knowledge about the 3D architecture of microvessels would be useful for determining the utility and limitations of two‐dimensional (2D) measures, as well as for determining the usefulness of 3D measures to predict pathologic stage and patient outcome in prostate cancer. However, the ability to study microvessels in 3D must first be demonstrated.

Desmoplastic Melanoma of the Head and Neck: Histopathologic and Immunohistochemical Study of 28 Cases

Studies of the immunohistochemical profiles and clinical course of desmoplastic melanoma have produced conflicting results. We identified 28 cases of desmoplastic melanoma after a search of our files for spindle cell neoplasms of the head and neck from 1960 through 1995. The 17 male (61%) and 11 female (39%) patients averaged 65 years of age. The cheek was the most common location (12 cases, 43%). The average length of follow-up was 5 years. Overall 5-year survival rate was 46%. Melan A and tyrosinase positivity (P = 0.0195), smooth muscle actin positivity (P = 0.0328), tumor size (P = 0.0297), and tumor thickness (P = 0.0419) were significantly associated with local progression-free survival. No histologic or immunohistochemical marker was associated with overall or metastasis-free survival.

Robust 3-D Reconstruction and Analysis of Microstructures from Serial Histologic Sections, with Emphasis on Microvessels in Prostate Cancer

We have developed a technique to reconstruct 3-D microstructures from serial histologic section, and demonstrated the robustness of the method on microvessels associated with prostate cancer and bile ducts in liver specimens. The method is critically based on image coregistration techniques, particularly two dimensional surface matching between extracted image features. The reconstruction paradigm allows 3-D regions of information in several locations throughout a block of tissue to be obtained at different magnifications while maintaining proper spatial relationship to the original data. The reconstructed objects have a generally unmapped and unknown topography. Visualizing anatomic microstructures in 3-D and analyzing their topography will help physicians to better understand and correctly interpret changes in disease.

Creation and Validation of Patient Specific Anatomical Models for Prostate Surgery Planning Using Virtual Reality

Prostate surgery to remove cancer can be associated with morbidity due to complex and variable individual anatomy. We have developed and demonstrated the ability to accurately extract patient-specific anatomic regions from MRI pelvic scan data of pre-prostatectomy patients and to effectively convert these volume images to faithful polygonal surface representations of anatomic models for use in interactive virtual surgical planning. Models of the prostate gland and surrounding structures from several patients were created then evaluated by a radiologist and a surgeon who found them to be faithful and consistent with real anatomy. The surgeon provided confirming post-operative validation of the patient-specific models in planning radical prostatectomies.

Three-dimensional visualization and analysis of microvessels in prostate cancer

A significant increase in diagnostic incidence of prostate cancer underscores the need to accurately stratify and quantify the cancers to facilitate appropriate therapy. Currently, there is no reliable method to preoperatively predict pathological stage and thus malignant potential of prostate cancer. Tumor volume and microvessel density have been shown postoperatively to be accurate predictors of cancer metastatic potential. 3D visualization and analysis of image volumes produced from series of immunocytochemically stained pathological sections may improve our understanding of the relationships of the tumor to angiogenesis, i.e., to the microvessel density of the tumor. Sequential thinly sliced (approximately 7 microns) pathological sections of the prostate will be differentially stained with fluorescent antibodies to clotting factor VIII- related antigen, which labels the endothelial cells of the vessels, facilitating automated color separation for visualization of the microvessels. Digitized images of the sections can be synthesized into 3D volumes and measured to quantify vessel quantity and density. Using 3D colorwash and transparency display techniques, anatomic and densitrometric relationships between the tumor and microvessels can be visualized. The microvessel density can be measured using image processing algorithms and compared to measurements made by pathologists. Advanced approaches to imaging the prostate in vivo include dynamic MRI techniques using contrast agents to accurately detect and quantify the region of prostate cancer. The cancerous region can be correlated with histologic specimens using the same methods described for measurement of microvessel density. This detailed information could lead to improved methods to properly stratify patients with diagnosed prostate cancer.