Histologic transformation of polymorphous low-grade adenocarcinoma of salivary gland.

Polymorphous low-grade adenocarcinoma of salivary gland origin (PLGA) was initially described in 1984 and has since become an established clinicopathologic entity. Owing to the indolent nature of PLGA and its relatively recent description, the full clinicopathologic spectrum of this entity has not been elucidated fully. Transformation to a histologically different-appearing lesion or progression to a higher histologic grade has not been reported. We describe 2 PLGAs arising in the palate and associated with multiple locoregional recurrences that were treated with excision and radiation therapy. This was followed by histologic transformation to a higher grade neoplasm after 17 and 26 years, respectively. The histologic appearance after transformation was characterized by a predominantly solid and cystic growth pattern, nuclear atypia with prominent nucleoli, and foci of necrosis. High-grade transformation of PLGA may occur after a protracted clinical course with multiple recurrences of typical PLGA. The possible role of radiation therapy as an initiator of this transformation merits further study. Tumors with these histologic features should not be included under the rubric of typical PLGA. Segregation of these neoplasms will allow further study of their biologic potential, particularly with regard to possible increased rates of local recurrence and metastasis.

Inhibin is not an immunohistochemical marker for hepatocellular carcinoma. An example of the potential pitfall in diagnostic immunohistochemistry caused by endogenous biotin.

Inhibin is a heterodimeric glycoprotein originally detected in gonadal tissues. One report described inhibin immunopositivity in 17 of 19 hepatocellular carcinomas (HCCs) and the hepatocytes of the surrounding nonneoplastic parenchyma. The reported immunohistochemical method, which used avidin-biotin complex, did not describe blocking endogenous biotin. Since liver tissue may contain high levels of biotin, endogenous biotin may result in false-positive immunostaining. We wondered whether this reported immunopositivity represented a false-positive result due to unblocked endogenous biotin. By using a similar antigen retrieval technique and the same specificity, titer, and clonal source of primary antibody as the aforementioned study, we performed immunostaining for inhibin with and without an endogenous biotin blocking step on 23 cases of HCC and the surrounding cirrhotic liver. In all cases, the HCC and the hepatocytes in the cirrhotic nodules were negative for inhibin when the endogenous biotin blocking step was used. When the blocking step was omitted, apparent immunostaining was noted in 20 of 23 HCCs and in the hepatocytes in all cases. Accordingly, HCC and the hepatocytes of the surrounding cirrhotic liver are immunohistochemically negative for inhibin. The previously reported immunopositivity of HCC and nontumoral hepatocytes for inhibin represents a false-positive result due to endogenous biotin.

Detection of the alpha-subunit of inhibin in trophoblastic neoplasia.

Placental trophoblasts are the primary source of serum inhibin during pregnancy. We sought to characterize inhibin immunolabeling in trophoblastic neoplasms and compare the results with those for established markers of trophoblastic differentiation. Formalin-fixed, paraffin-embedded tissues from three normal term placentas, 13 hydatidiform moles (HM), five choriocarcinomas (CC) (three gestational, one testicular, one mediastinal), and five placental site trophoblastic tumors (PSTT) were immunolabeled with antibodies to the alpha-subunit of inhibin, hPL, and beta-hCG. Additionally, six first-trimester placentas were immunolabeled with antibody to inhibin alone. Trophoblastic subpopulations were assessed for the number of positive cells (1% to 24% = 1+,25% to 49% = 2+,50% to 74% = 3+, 75% to 100% = 4+). Immunolabeling in term placenta and HM was similar, because beta-hCG was the most sensitive marker (4+) of syncytiotrophoblasts followed by inhibin (3-4+) and hPL (2-3+). Immunolabeling of syncytiotrophoblasts in CC was similar to that in term placenta and HM, except for negative hPL staining in two cases. In HM, inhibin labeling of intermediate trophoblasts (2-3+) was less than that for hPL (3-4+). In CC, inhibin and hPL labeling of intermediate trophoblasts was more variable with negative hPL reactivity in two cases. Inhibin and hPL did not stain cytotrophoblasts. In PSTT, inhibin immunolabeling was a better marker than hPL in two cases, inferior in two, and similar in one. Inhibin labeling of syncytiotrophoblasts was less than that for beta-hCG, but did not have the often marked background staining that was present with beta-hCG. Immunolabeling of trophoblast subpopulations for inhibin was similar between first-trimester placenta, term placenta, and HM. We conclude that inhibin is a useful immunohistochemical marker of trophoblastic neoplasia and should be included in the antibody panel with beta-hCG and hPL.

The alpha subunit of inhibin in adrenal cortical neoplasia.

We analyzed 23 adrenal adenomas and 15 adrenal cortical carcinomas by immunolabeling for the alpha subunit of inhibin, and we then compared the results with the functional status of the neoplasms. We also studied 19 pheochromocytomas, 30 renal cell carcinomas, and 5 extra-adrenal paragangliomas, tumors posing differential diagnostic problems with adrenal cortical neoplasms. Immunolabeling was performed using automated immunohistochemical methods and an antibody directed against the alpha subunit. Tumors were semiquantitatively assessed for the number of positive cells. Immunopositivity was obtained in 18 (78%) of 23 adrenal cortical adenomas, 12 (80%) of 15 adrenal cortical carcinomas, 2 (11%) of 19 pheochromocytomas, 0 of 5 extra-adrenal paragangliomas, and 0 of 30 renal cell carcinomas. Immunoreactivity was strong in 7 (78%) of 9 adrenal cortical tumors from patients with Cushing's-related or virilizing symptoms. In contrast, only 4 (14%) of 29 tumors that were clinically nonfunctioning or associated with hyperaldosteronism demonstrated strong staining (P < .001). In clinically nonfunctioning tumors, there was a tendency for increased immunopositivity in tumors from patients with elevated levels of cortisol, androgen, or their precursors, with four of six tumors having at least moderate immunopositivity. Similar reactivity was present in only one of eight tumors from patients with normal laboratory values (P=.091). Moderate or strong immunopositivity was present in 9 (60%) of 15 adrenal cortical carcinomas, whereas of the pheochromocytomas, extra-adrenal paragangliomas, and renal cell carcinomas, only 1 (1.9%) of 54 showed moderate-to-strong reactivity. We conclude that moderate or strong immunoreactivity for the alpha subunit of inhibin occurs in adrenal cortical tumors from patients with Cushing's-related or virilizing symptoms. Immunolabeling for the inhibin alpha subunit is potentially useful in the differential diagnosis of neoplasms that include adrenal cortical carcinomas.

The diagnostic utility of inhibin staining in ovarian neoplasms.

Previous immunohistologic studies have suggested that the antibody to the alpha subunit of inhibin is a sensitive marker of sex cord-stromal differentiation. However, detection has also been reported within both ovarian epithelial and germ cell tumors. To further study the normal tissue distribution of inhibin and the utility of its detection for the differential diagnosis of ovarian sex cord-stromal neoplasms, normal tissues and 225 lesions including sex cord-stromal lesions, ovarian epithelial and stromal cancers, ovarian and testicular germ cell tumors, metastases to the ovary, and non-ovarian cancers were analyzed using semi-automated immunohistochemistry. In normal tissues, immunostaining was found in cell subsets of the ovary, testis, adrenal gland, placenta, and kidney. All sex cord-stromal tumors were inhibin-positive and 37 of 50 (74%) cases exhibited at least moderate to strong immunostaining. Two cases originally diagnosed as adult granulosa cell tumors that were inhibin-negative were reassessed; diagnoses of endometrioid stromal sarcoma and endometrioid carcinoma with sertoliform features were rendered. In other primary or metastatic ovarian lesions or metastases to the ovary, weak to moderate immunostaining was found in only 4 of 84 (4.8%) cases, including ovarian clear cell carcinoma (2/2), uterine clear cell carcinomas metastatic to the ovary (1/3), and serous papillary carcinoma (1/2). Similarly, only 4 of 66 (6.1%) non-ovarian neoplasms exhibited weak immunostaining, including melanoma (1/5), uterine endometrioid carcinoma (1/2), transitional cell carcinoma (1/3), and breast adenocarcinoma (1/8). Only one case of a non-sex cord-stromal tumor had moderate or strong immunostaining. Based on these results, immunohistologic detection of the alpha subunit of inhibin is a useful adjunct in the differential diagnosis of sex cord-stromal neoplasms.

Giant glioependymal cyst resembling holoprosencephaly on prenatal ultrasound: case report and review of the literature.

We report the earliest in utero presentation of a 'giant' glioependymal cyst detected on routine prenatal ultrasound at 22 weeks estimated gestational age. The clinicopathologic features of these rare lesions are reviewed as well as previous reports of glioependymal cysts detected in utero. The effects of large intracranial cysts on neurodevelopment are discussed as well as the differential diagnosis of infantile intracranial cysts and therapeutic alternatives.

Molecular and immunological detection of circulating tumor cells and micrometastases from solid tumors.

Histological, immunological, and molecular methods have been used for detecting micrometastases from nonhematopoietic malignancies. Early studies utilizing cytological methods to identify circulating tumor cells demonstrated the uncertain significance of micrometastasis detection for predicting eventual recurrent disease. Recently, reverse transcriptase-polymerase chain reaction (RT-PCR) for the detection of circulating tumor cells has been suggested as a potential technique for staging of cancer. Studies using RT-PCR thus far indicate that test results may be negative in some patients with known metastatic disease, thereby raising doubts about the utility of the method for staging of disease. In this review, we survey the relevant literature and discuss the range of current applications of histological, immunological, and molecular methods for detecting micrometastases from solid tumors in blood, bone marrow, and lymph nodes and the progress toward determining the significance of micrometastasis detection.

Minimal physiologic temperature variations during renal ischemia alter functional and morphologic outcome.

Aortic and renal vascular reconstruction often involve significant renal ischemia. Profound hypothermia during renal ischemia preserves renal tissue. However, in the clinical setting of vascular reconstruction specific attempts at cooling the kidney are often impractical, and renal ischemia frequently occurs at physiologic temperatures. This study demonstrates that minimal temperature changes during renal ischemia alter the functional and morphologic outcome. Rats anesthetized with halothane underwent a right nephrectomy and placement of a snare around the left renal pedicle for 45 minutes to produce renal ischemia. Seventy-five adult male Sprague-Dawley rats, weighing 250 to 350 gm were divided into three groups based on the body temperature maintained during renal ischemia (35 degrees C, 37 degrees C, 39 degrees C). Body temperature was continuously monitored with a rectal thermistor and maintained by adjustment of a heating pad and lamp. Two postischemic protocols were followed including a creatinine assessment protocol with blood samples collected at 24, 48, and 72 hours and a histologic assessment protocol with biopsy of the kidney at 30 hours. At 24 hours after ischemia plasma creatinine concentrations were increased in rats with elevated body temperatures (35 degrees C vs 37 degrees C; [p = 0.001], 37 degrees C vs 39 degrees C; [p = 0.150]). The 30-hour histologic assessment indicated a difference in morphologic outcome (35 degrees C vs 37 degrees C; [p = 0.063], 37 degrees C vs 39 degrees C; [p = 0.016]), with proximal tubular morphology being better maintained at lower temperatures.(ABSTRACT TRUNCATED AT 250 WORDS)