The dimensions and symmetry of the seminal vesicles.

The traditional anatomical description of the seminal vesicles is based on autopsy and imaging studies. Trans-peritoneal robotic-assisted laproscopic surgery, with its three-dimensional magnified view and miniature articulated working instruments, provides an opportunity to perform accurate dissections of the seminal vesicles even when extremely long and tortuous. We used specimens obtained by robotic-assisted laparoscopic radical prostatectomy (RLRP) for accurate anatomic assessment of the dimensions of the seminal vesicles. Digital photos of 78 specimens from men (mean age 59 ± 6.1 years) who underwent RLRP were analyzed using the Image Pro Plus software. Seminal vesicle dimensions were correlated with patients' age, weight, height, prostate weight, sexual function profile (SHIM) and symptom severity score of the lower urinary tract symptoms (IPSS). We found that the length of the seminal vesicles is highly variable (range of 8.5-94.6 mm). The average seminal vesicle length was 31 ± 10.3 mm and its average volume 7.1 ± 5.2 ml. The right seminal vesicle was significantly larger than the left in length, width and volume (P < 0.003). The seminal vesicles were found to be highly asymmetric with a mean difference of 17.8% in length and 24.9% in width between the sides. No correlation between seminal vesicle dimensions and any of the parameters tested was found. We concluded that the normal human seminal vesicles are characterized by marked (11-fold) variation in length and are asymmetric in most patients. The right seminal vesicle is significantly larger than the left. Seminal vesicle dimensions cannot be predicted from other morphometric or physiologic parameters.

Up-regulation of MKK4, MKK6 and MKK7 during prostate cancer progression: an important role for SAPK signalling in prostatic neoplasia.

Identification of the signalling cascades that are differentially activated during prostatic tumourigenesis is a crucial step in the search for future molecular targets in this disease. The stress-activated protein kinase (SAPK) signalling cascade culminates in the phosphorylation of the JNK and p38 mitogen-activated protein kinases (MAPKs). Recently, the upstream activators of these proteins, the MAPK kinases (MKKs), have been implicated as inhibitors of tumour progression in a variety of clinical and experimental tumour models. This study evaluates MKK4, MKK6 and MKK7 expression during prostate cancer progression in humans and in the transgenic adenocarcinoma of a mouse prostate (TRAMP) model of prostate tumourigenesis. Benign prostate, prostatic intraepithelial neoplasia (PIN) lesions and tumour tissues were collected from 37 TRAMP mice. Additionally, six tissue microarrays were constructed with tumours from a matched group of 102 men who underwent radical prostatectomy. Tissues from 20 patients with extensive high-grade prostatic intraepithelial neoplasia (HGPIN) were also analysed. For all samples, immunohistochemical staining for MKK4, MKK6 and MKK7 was scored in normal and neoplastic glands. Staining intensities of MKK4, MKK6 and MKK7 were significantly increased in HGPIN and prostate cancer compared to surrounding normal glands in both the TRAMP and human samples (p < 0.0001 for all markers). Increased levels of MKK4 or MKK7 correlated with higher pathological stage at prostatectomy (p = 0.01 and p = 0.04). Using multivariate analysis, there was no association between protein levels and time to biochemical recurrence in the human samples. The up-regulation of MKK4, MKK6 and MKK7 during prostate cancer progression in both TRAMP and human tissues highlights an important role for the SAPK signalling cascade in prostatic neoplasia. The finding that higher MKK4 and MKK7 expression is associated with higher-stage prostatic tumours underscores the dynamic regulation of these proteins during prostatic tumourigenesis.

Squamous carcinoma in a major salivary gland: a review of the diagnostic considerations.

CONTEXT: Squamous carcinoma in a major salivary gland has several possible sources: (1) high-grade mucoepidermoid carcinoma, (2) metastasis or direct invasion from a primary skin carcinoma, (3) metastasis from a distant primary carcinoma, or (4) a primary malignant neoplasm. The latter is conventionally regarded as a diagnosis of exclusion after a history of squamous carcinoma elsewhere has been obtained or there is a positive mucin stain. DESIGN: Eleven cases of squamous carcinoma in a major salivary gland are presented and the literature reviewed. RESULTS: Two cases, 1 metastatic from a histologically identical squamous carcinoma from the ipsilateral tonsil and 1 with in situ squamous carcinoma in a duct, demonstrated positive mucicarmine stains. Two cases were high-grade mucoepidermoid carcinomas, also with positive mucin stains. Five cases represented metastases from cutaneous squamous carcinomas. Only 2 cases were regarded as primary carcinomas. There were no histologic clues as to correct subclassification. Six patients died, 4 from their disease. Three of the 5 still alive had recurrence or metastasis. CONCLUSION: The occurrence of squamous carcinoma in a major salivary gland exhibits a histologic sameness that precludes accurate subclassification and assignation of origin. Also irrespective of tumor origin, the clinical approach to diagnosis and treatment is similar. Adjuvant therapy (eg, radical neck dissection, radiation, chemotherapy) is not uniformly applied. Most patients present with a sizable (>3-cm) mass for which total excision is attempted. The natural evolution of the tumor is aggressive, irrespective of clinical context. The traditional subclassification of squamous carcinoma in a major salivary gland may not be clinically relevant.

Proliferation markers and prognosis in Merkel cell carcinoma.

Merkel cell carcinoma (MCC) is a frequently aggressive primary cutaneous neuroendocrine malignancy. We investigated 3 cell proliferation markers which may be useful in predicting the aggressiveness of MCC: 1) p53, a tumor suppressor protein, 2) Ki-67, a marker of cell cycling, and 3) proliferating cell nuclear antigen (PCNA). Twenty patients with MCC were studied. The 3 cell proliferation markers were studied by immunoperoxidase. Clinical and immunoperoxidase results were tabulated according to recurrence or death from disease. Of the 20 patients, 10 experienced recurrence, and 10 did not. Seven tumors were positive for p53. We found correlations between recurrence and death in MCC patients, between p53 positivity and recurrence/death, and between p53 positivity and head/neck primary sites. We found no correlation with recurrence by gender or primary site. PCNA was positive in only 1 patient, while Ki-67 was positive in all patients, making these 2 markers unsuitable for predicting recurrence. Further clinical studies will be helpful to confirm and refine the application of this test. Prognostic information from such studies may be useful in planning observation and treatment for patients in the future.

Squamous carcinoma of the nasal vestibule: an analysis of five cases and literature review.

Five examples of squamous carcinoma of the nasal vestibule are reported. Possibly because this keratinizing tumor is histopathologically identical to squamous cancer in other locations, reports of this tumor in the pathology literature are uncommon. The patients were four men and one woman, of whom three men were smokers, although there are no consistent published associations with any environmental toxins to determine patients at risk. All five patients had localized disease treated by combinations of surgery and radiation therapy. Flap reconstructions and skin grafting were used in three patients; two patients underwent nasal amputations. Three patients also received postoperative irradiation. Three patients experienced recurrences from 2 to 13 years after the original treatment; there were no deaths related to this tumor. Histologically, these are typically ulcerated tumors seldom showing evidence of in situ carcinoma. Surgical margins of excision were positive or close in three cases but did not influence the chronic course of the disease. No clinical tumor staging system is generally accepted, and it seems that the prognosis for localized disease is good irrespective of clinical stage. Aggressive features, including penetration of cartilage and invasion of overlying skin, may be impressive, but do not preclude long-term survival if bulk disease can be surgically removed.

Long-term survival and DNA ploidy in advanced epithelial ovarian cancer.

BACKGROUND AND OBJECTIVES: The relationship of the tumor DNA content to survival of patients with advanced epithelial cancer has not yet been clarified. A large amount of contradictory data exists in the literature. This study analyzes the putative relationship between ploidy and advanced ovarian carcinoma. METHODS: A retrospective analysis of tumor ploidy, DNA index, and the S-phase fraction from 35 patients with nonborderline epithelial ovarian carcinomas was determined by flow cytometry of paraffin-embedded tissue. All patients had FIGO stage III or IV disease. Those patients who survived > 5 years were assigned to Group A (10 patients). Group B consisted of 25 age-matched subjects who succumbed to their disease within 5 years of diagnosis. RESULTS: Group A had not reached a median overall survival with a median follow-up of 114 months (range 67-226), whereas Group B had a median overall survival of 17 months (range 1-48). Two of the patients in Group A and all of the patients in group B had died of the disease. The two groups were similar in age, histologic type, and treatment. In Group A, three patients had grade 1 tumors, in contrast to group B where all the patients had either grade 2 or 3 disease (P = 0.018). However, the distribution of aneuploidy was similar in both groups. Also, the DNA indices were similar: 1.40 +/- 0.42 in Group A, and 1.36 +/- 0.44 in Group B. The median S-phase fraction was 14% (range 3-23%) in Group A, and 15% (range 2-23%) in Group B. The grade and type of tumor were not related to the ploidy or the DNA index. There was no significant correlation between ploidy or the DNA index and survival. CONCLUSION: This study suggests that the DNA content of tumor as measured by flow cytometry is not a predictor of long-term survival in ovarian cancer patients with advanced disease.

Neoadjuvant chemotherapy in uterine papillary serous carcinoma.

Uterine papillary serous carcinoma (UPSC) is an aggressive variant of endometrial cancer that frequently imitates serous carcinoma of the ovary in its clinical presentation and histologic appearance. Unlike the ovarian lesion, however, it is known to be particularly resistant to chemotherapy. A patient with a putative diagnosis of unresectable Stage IV ovarian cancer was treated with three cycles of neoadjuvant chemotherapy containing paclitaxel and carboplatin. After a remarkable response, interval cytoreductive surgery was performed. A primary endometrial tumor with the pathologic features of UPSC was found. To our knowledge, the use of paclitaxel-containing chemotherapy in UPSC has not been reported. We suggest that this therapy might be useful in the treatment of patients with advanced uterine papillary serous carcinoma, as well as in an adjuvant setting.

Breast cancer metastatic to the uterus. Clinical manifestations of a rare event.

Adenocarcinoma of the breast rarely metastasizes to the mucosal surfaces of the uterus. We present two patients with endometrial involvement, in one of whom it was the initial manifestation of her breast cancer. Two additional patients with cervical involvement had abnormal Papanicolaou smears and grossly normal cervices. One of these patients underwent a biopsy, the results of which confirmed metastatic adenocarcinoma. Three of the four patients had previously well-established metastatic disease. The presence of genital, especially mucosal, metastases is indicative of widespread disease and imminent demise. This occurred in one of the patients described here; however, another patient survived 30 months. Breast cancer is a chronic disease for which the metastatic behavior is exceptionally unconventional. Tissue acquired by endometrial curettage or colposcopy may require an awareness on the part of the pathologist to such a clinical circumstance.

Role of the autopsy in congenital cystic hygroma.

Sixteen cases of congenital cystic hygroma were identified through a retrospective review of surgical pathology and autopsy records. Tissue sections of the cystic hygromas were available in 10 cases and were examined histopathologically and for reactivity to factor VIII antiserum. Of 13 cases with ultrasound examinations, cystic hygroma was diagnosed prenatally in 9. In 11 cases with successful karyotyping, six were 45, X. Histopathologic observations of lymphatic vascular architecture were apparent in 10 cases, and immunoreactivity of the endothelium to factor VIII antiserum was preserved regardless of the degree of autolysis.

Necrotizing squamous/mucinous metaplasia in oncocytic salivary gland tumors. A potential diagnostic problem.

Tumor necrosis and squamous and/or mucinous metaplasia was found in 4 of 26 oncocytic salivary gland tumors (24 Warthin's tumors and 2 oncocytomas). The necrosis was extensive in two cases, producing architectural and cytologic atypia sufficient to simulate a squamous carcinoma. In a third tumor, necrotic and inflammatory debris occurred within dilated tumor spaces exhibiting squamous and mucinous foci, suggesting low-grade mucoepidermoid carcinoma. Adequate sampling revealed Warthin's tumors in all four cases. An additional 13 tumors showed incidental foci of squamous metaplasia, often accompanied by stromal scarring but without necrosis. Four of these tumors also had focal mucinous metaplasia. In the adjacent non-neoplastic salivary gland, oncocytic metaplasia of ducts was seen in 22 glands; there were 7 oncocytic cysts and 3 oncocytic nodules. The tumor necrosis and metaplasia are reminiscent of necrotizing sialometaplasia of the minor salivary gland, thought to be ischemic in origin. The etiology of necrotizing squamous/mucinous metaplasia described here and the extent to which oncocytosis contributes to these changes is unknown. Possibly the extravasation of oncocytic and/or mucinous secretions or cyst contents may result in the reactive changes observed. Necrotizing sialometaplasia and squamous/mucinous metaplasia of oncocytic tumors appear to be related only morphologically, but the shared histologic features may be useful in excluding the diagnosis of salivary gland carcinoma.

Meningioma of the paranasal sinuses. A report of two cases.

Two patients presented with primary meningiomas arising in the paranasal sinuses. Despite nonspecific symptoms, both patients had extensive local clinical disease. One patient had a lateral rhinotomy with total removal of tumor; he has remained well for 3 years. The second patient, who was not a surgical candidate because of her cerebrovascular disease, was identified retrospectively. Her tumor was not originally studied using current day morphologic methods. She was irradiated following a diagnosis of malignant tumor. The histologic features of nasal meningioma are similar to those of conventional intracranial lesions, including nuclear pseudoinclusions. Although the unusual location may suggest carcinoma, melanoma, or olfactory neuroblastoma, adjunctive use of electron microscopy and immunohistochemistry can be combined to arrive at the correct diagnosis.

The intrathyroidal hyperfunctioning parathyroid gland.

Six cases of primary hyperparathyroidism due to hyperfunctioning intrathyroidal parathyroid glands are reported. In five cases, hyperparathyroidism was due to an intrathyroidal parathyroid adenoma; in the sixth case, hyperparathyroidism resulted from an intrathyroidal parathyroid carcinoma. All five patients with adenoma were female with ages ranging from 40 to 70 yr. The patient with carcinoma was a 55-yr-old male. In all five patients with intrathyroidal parathyroid adenoma, thyroidectomy was performed when an abnormal parathyroid gland could not be located in the neck during surgery for hyperparathyroidism. The patient with intrathyroidal parathyroid carcinoma presented with hypercalcemia and a palpable right thyroid mass. The differential diagnosis of intrathyroidal parathyroid adenoma includes thyroid follicular adenoma. In some cases, the possibility of medullary carcinoma of thyroid might also be considered. Immunocytochemical staining for parathormone (PTH), thyroglobulin, and calcitonin is valuable in establishing the correct diagnosis.

Anal cancer. Microscopic condyloma and tissue demonstration of human papillomavirus capsid antigen and viral DNA.

Sixteen cases of squamous cell carcinoma of the anus, including 4 incidentally discovered in situ lesions, and 3 anal condylomas, were examined for the presence of human papillomavirus (HPV). All in situ tumors and 6 of the invasive tumors were associated with histologic changes typical of condyloma, despite the absence of clinical anogenital warts. Immunohistochemical studies for viral capsid antigen gave positive reactions in two anal warts and in the condylomatous area associated with one invasive tumor. In situ hybridization was accomplished using isotopic DNA probes for HPV 6/11, 16, 18, and 31. Human papillomavirus 6/11 was expressed in the corresponding capsid-positive regions in the two warts and the wart-associated invasive carcinoma. Both HPV 6/11 and HPV 16 were associated with one carcinoma in situ, and HPV 16 was also found within two invasive anal carcinomas, one of which was associated with an extensive vulvar cancer. While these observations do not resolve the "passenger" or direct oncogenic role for HPV in anal carcinoma, the circumstantial evidence is that the oncogenic influence is similar to that accepted for female genital tract cancer.