International Journal of Surgical Pathology

MN protein is the product of the newly described endogenous MN gene that is expressed in the tumorigenic phenotype of HeLa X fibroblast somatic cell hybrids. MN protein has carbonic anhydrase and putative DNA binding activity. With the exception of gastric mucosa, MN protein is expressed in neoplasia, particularly uterine cervix carcinoma, but not in benign tissue. This investigation examined the pathogenetic and prognostic significance of MN-protein immunoreactivity in uterine cervix carcinoma with glandular differentiation. Paraffin sections from 77 cervix carcinomas with glandular differentiations including 36 pure adenocarcinomas and 41 adenosquamous carcinomas were immunostained with anti-MN-protein (M-75 monoclonal proprietary; Ciba Corning Diagnostics, Alameda, CA). A total of 64.9% of cervix carcinomas with glandular differentiation exhibit MN-protein immunoreactivity localized to plasma membranes, cytoplasm, and some nuclei of neoplastic cells only, but not in adjacent benign tissue. The MN-protein staining intensity and distribution was as follows: 37.7% strong diffuse (≥ 50% cells positive), 19.5% strong focal (< 50% cells positive), and weak (7.8%). Immunoreactivity occurred in both squamous and glandular areas of adenosquamous carcinomas and was unrelated to histopathologic features. Follow-up information was available on 67 patients: 31 exhibited recurrent disease (7 pelvic, 14 distant, and 10 both) at 1–144 months (mean 37, median 14), and 36 were disease-free at 12–216 months (mean 67, median 44.5). MN-protein immunoreactivity (all positives, both standard diffuse and strong focal, or standard diffuse only) exhibited no association with clinical outcome. Recurrent disease was associated with nuclear grade (P < .001), lymphatic invasion (P < .005), size on clinical examination or pathologic evaluation (P < .005), pelvic lymph node involvement (P < .05), and clinical stage (P < .05). MN-protein immunoreactivity did not correlate with these features and did not help predict which patients would develop recurrence in the good prognosis groups. Our data show that expression of MN-protein is associated with cervix carcinoma with glandular differentiation carcinogenesis. MN-protein immunolocalization may have a diagnostic role in confirming cervix carcinoma with glandular differentiation in histologically challenging cases.

Eighty-five lesions of pure, noninvasive intraductal carcinoma were analyzed by histologic subtypes. The comedo subtype, defined by a solid growth pattern, high nuclear grade, and central necrosis, accounted for only seven lesions (8.2%). Solid, micropapillary, or cribriform patterns with central necrosis comprised 16 cases (18.8%), micropapillary 19 (22.4%), and cribriform 22 (25.9%). The comedo subtype showed several features different from the other subtypes. They occurred in younger patients and had higher numbers of duct profiles with carcinoma and larger tumor diameters. The intensities of lobular cancerization and periductal stromal chronic inflammation were also marked in the comedo lesions. Two of three comedo lesions examined by flow cytometry showed aneuploidy. Three of five tumors with nipple involvement contained at least some comedo-type duct profiles. These findings indicate greater potential aggressiveness of the comedo subtype. In contrast, the micropapillary and cribriform subtypes had fewer involved duct profiles, lower nuclear grade, and less mitotic activity. Microcalcification identified histologically, multifocality, and multicentricity were present in 54.1, 74.1, and 13.8%, respectively, of all lesions examined, and there were no differences between subtypes. Thus, the operative treatment of the comedo subtype (based on spread of disease within the breast) may not need to be more extensive than for other types of intraductal carcinoma. Central necrosis may prove to be of considerably less importance than nuclear grade in future evaluations of intraductal carcinoma.

Ki-ras codon 12 mutation was detected in: (1) surgically resected formalin-fixed and paraffin-embedded specimens from 109 carcinoma cases, including 46 pancreatic, 35 ampullary, 24 extrahepatic bile duct, and 4 gallbladder carcinomas, showing prevalences of 95.7%, 5.7%, 8.3%, and 0%, respectively, by polymerase chain reaction-restriction fragment length polymorphism technique, and 89.1%, 2.9%, 8.3%, and 0%, respectively, by polymerase chain reaction-dot blot method; and (2) 35 consecutive fine-needle aspiration biopsy specimens by polymerase chain reaction-restriction fragment length polymorphism giving a positive rate of 94.7% (18/19) for pancreatic carcinoma and 0% (0/16) in the specimens from nonpancreatic carcinoma tissues or tumors. Our results demonstrate that the strikingly high prevalence of Ki-ras codon 12 mutation of pancreatic carcinoma could be used as an effective means in the diagnosis and differential diagnosis of pancreatic carcinoma.

Cellular fibronectin mediates the adhesion of cells with the extracellular matrix and thus probably regulates tumor invasion. Evaluation of proliferating cell nuclear antigen expression and counting of silver nuclear organizer regions potentially assess proliferative fraction and biologic aggressiveness in several malignancies. We investigated the above markers’ prognostic value in 60 malignant melanomas of the skin. Deep Clark levels were statistically associated with discontinuous fibronectin staining pattern (SPII) (P < .05) as well as with high proliferating cell nuclear antigen and silver nuclear organizer regions indexes (P < .01 and P < .05, respectively). Fibronectin staining pattern (SPII) was frequently observed in thick melanomas (P < .05). High proliferating cell nuclear antigen immunoreactivity positively correlated with mitotic activity (P < .05), the presence of vertical growth phase (P < .05), and increased silver nuclear organizer regions counts (P < .05). Patients with continuous fibronectin staining pattern (SPI) and low proliferating cell nuclear antigen scores were unlikely to develop metastatic disease (P < .01). Therefore, the simultaneous comparative assessment of these factors is very promising in predicting melanomas clinical evolution.

The clinical details and radiologic and histopathologic findings of lesions from three male siblings and their female cousin with hyperphosphatemic tumoral calcinosis are presented. The three siblings were children of consanguineous parents. The patients were aged 5, 17, 19, and 20 years; however, they first presented when they were 3.5, 8, 4, and 5 years of age, respectively; resulting in a disease duration ranging from 1.5 to 15 years. All are alive with persistent disease. The eldest patient has an alpha-thalassemia trait. Sites of lesions included the periarticular soft tissues of gluteal region, the shoulder, elbow, interscapular area, axilla, and popliteal fossa. A calcified soft tissue mass was seen radiologically at all sites affected. Histologically, locules of calcified debris surrounded by multinucleated osteoclast-type giant cells and foamy histiocytes characterized all lesions. The cells showed cytoplasmic vacuoles that stained positively both with anti-alpha-1-antichymotrypsin and anti-alpha-1-antitrypsin. Ultrastructurally hydroxyapatite deposits were demonstrable in these cytoplasmic vacuoles. All patients had normocalcemia and hyperphosphatemia. A low normal blood level of 25-hydroxycholecalciferol was noted in the youngest patient. Surgical excision was unsuccessful as the lesions recurred and progressed. Medical therapy may only slow the progression of the disease process.

Thirty-three specimens from 25 transplant recipients with Epstein-Barr virus-associated lymphoproliferative disease were studied by in situ hybridization for 2 lytic and 4 latent Epstein-Barr virus transcripts. All specimens were found to contain at least 1 latent transcript while 28 were positive for at least 1 lytic transcript. The amount of Epstein-Barr virus infection and lytic activity varied with histopathology and number of involved sites. Patients with localized polymorphous disease contained the lowest number of infected cells with an almost equal lytic:latent ratio. Disseminated polymorphous and single and multisite monomorphous specimens showed a large latent cell population. Minimal lytic activity was seen in single site monomorphous specimens, but disseminated monomorphous specimens showed the highest levels of lytic transcripts. Most post-transplant lymphoproliferative disorder specimens demonstrate lytic Epstein-Barr virus transcripts, although the majority of cells contain latent Epstein-Barr virus. Lytic activity is highest in patients with disseminated disease. Lytic Epstein-Barr virus infection may aid in the development and maintenance of lymphoproliferative disorders in transplant recipients.

A case of pure extragonadal choriocarcinoma in the rectum of an 84-year-old man is described. The patient complained of rectal bleeding and lower abdominal pain. The trophoblastic origin of the tumor was documented by immunoperoxidase staining for human chorionic gonadotropin. The DNA histogram showed a diploid pattern. The patient died 106 days after diagnosis. Only eight cases of choriocarcinoma of the large intestine have been reported, three of which were located in the rectum. The age of patients affected range widely, from 28 to 84 years with a mean of 54 years: 79 for males and 46 for females. Women are affected three times as often as men. The pathologic study showed adenocarcinoma with germ cell elements in seven cases: six choriocarcinoma and one mixed (choriocarcinoma and endodermal sinus tumor). Germ cell differentiation may be difficult to identify in small biopsy samples, which may not be representative of the tumor as a whole. The prognosis of patients with choriocarcinoma of the large bowel is very poor; survival is less than 5 months. Although choriocarcinoma in the rectum is very rare, it should be included in the differential diagnosis of rectal neoplasms.

A rare case of gynandroblastoma of the right ovary with a typical morphologic appearance in a 10-year-old girl is reported. Clinically, there were both feminizing and masculinizing symptoms with elevated estradiol and testosterone levels. The pathomorphology, immunohistochemistry, and ultrastructural features of this tumor are described, and the reported cases in the literature are reviewed.

Heterotopic pancreas is not an uncommon finding in surgical or autopsy specimens. It may be asymptomatic or produce mechanical obstruction, surface ulceration, and other rarer complications. Cystic dilation of pancreatic ducts within heterotopic pancreas has been reported. This case report gives the clinicopathologic findings of heterotopic pancreas in a 37-year-old woman. It illustrates how cystic dilation of the pancreatic duct in heterotopic pancreas may masquerade as gastric duplication.