Mn-salen catalysed benzylic C-H activation for the synthesis of aryl [(18)F]CF3-containing PET probes.

The development of a Mn-salen complex catalysed oxidative benzylic fluorination of non-activated C-H bonds using [(18)F]fluoride is described for installation of [(18)F]CHRF, [(18)F]CR2F and particularly [(18)F]CF3 containing groups in the presence of other functional groups.

Reconstruction of the symphysis pubis to repair a complex midline hernia in the setting of congenital bladder exstrophy.

PURPOSE: A 40-year-old man with congenital midline defect and wide pubic symphysis diastasis secondary to bladder exstrophy presented with a massive incisional hernia resulting from complications of multiple prior abdominal repairs. Using a multi-disciplinary team of general, plastic, and urologic surgeons, we performed a complex hernia repair including creation of a pubic symphysis with rib graft for inferior fixation of mesh. METHODS: The skin graft overlying the peritoneum was excised, and the posterior rectus sheath mobilized, then re-approximated. The previously augmented bladder and urethra were mobilized into the pelvis, after which a rib graft was constructed from the 7th rib and used to create a symphysis pubis using a mortise joint. This rib graft was used to fix the inferior portion of a 20 × 25 cm porcine xenograft mesh in a retro-rectus position. With the defect closed, prior skin scars were excised and the wound closed over multiple drains. RESULTS: The patient tolerated the procedure well. His post-operative course was complicated by a vesico-cutaneous fistula and associated urinary tract and wound infections. This resolved by drainage with a urethral catheter and bilateral percutaneous nephrostomies. The patient has subsequently healed well with an intact hernia repair. The increased intra-abdominal pressure from his intact abdominal wall has been associated with increased stress urinary incontinence. CONCLUSIONS: Although a difficult operation prone to serious complications, reconstruction of the symphysis pubis is an effective means for creating an inferior border to affix mesh in complex hernia repairs associated with bladder exstrophy.

Encapsulated papillary neoplasms of the thyroid. A study of 14 cases followed for a minimum of 10 years.

Fourteen cases of encapsulated papillary thyroid neoplasm in which extracapsular extension was not observed and a minimum of 10 years follow-up was available are herein presented. The cases were divided into three categories: encapsulated papillary carcinomas (five cases), which had cytologic features typical of papillary thyroid carcinoma (vesicular or indented nuclei) and an entirely or predominantly thick capsule with capsular invasion; encapsulated papillary neoplasms of undetermined malignancy (seven cases), in which the cytologic features were also typical of papillary carcinoma but the capsule was predominantly thin (less than 0.1 mm thick) or was thick without capsular invasion; and follicular adenomas with papillae (two cases), which resembled follicular adenomas cytologically (rounded, stippled nuclei and Hürthle cell change) but contained a significant number of papillary structures (both cases had an entirely or predominantly thin capsule). The only evidence of malignant behavior in the entire series was a cervical lymph node metastasis in one case of encapsulated papillary carcinoma; the "encapsulated papillary neoplasms of undetermined malignancy" were so labeled because other authors have reported "encapsulated papillary carcinomas without capsular invasion" and it was therefore thought that the malignant potential of this category is as yet best considered undefined.

Low-grade fibromyxoid sarcoma. A report of 12 cases.

Twelve cases of low-grade fibromyxoid sarcoma are presented. The patients' ages ranged from 6 to 51 years; all but three were between 26 and 46 years of age. The tumor was located in the thigh or inguinal area in four patients, in the shoulder area in three patients, and in the axilla-chest wall area, the perineum, the small bowel mesentery, the neck, and the buttock in one patient each. Tumor size (maximum dimension) varied from 3.5 to 15 cm in the nine cases in which it was known (median, 9.5 cm). Histologically, the neoplasms demonstrated contrasting fibrous and myxoid areas, a swirling, whorled growth pattern (at least in part), and bland, deceptively benign-appearing fibroblastic spindle cells; cellularity was low to moderate, mitotic figures were uncommon, and nuclear pleomorphism was usually absent or slight. Focal histologic findings in a minority of the cases included increased perivascular cellularity, moderate nuclear pleomorphism (more often in recurrent tumors), and, in myxoid areas, a rich capillary vascular network (vascularity was usually not prominent). On follow-up, nine patients experienced local recurrence (from one to numerous times); recurrence was subsequently controlled in five cases but not in the remaining four. Distant metastasis occurred in seven cases, chiefly to the lungs, but two of these patients were rendered tumor-free (to latest follow-up) by excision of metastases. At latest follow-up, four patients had died of tumor at 8, 9, 31, and 31 1/2 years, respectively, three were alive with recurrent or metastatic tumor at 6 1/2, 12 1/2, and 50 years, respectively, and five were alive and tumor-free at 5 1/2, 10 1/2, 12, 22 1/2, and 44 years, respectively. One tumor, in the patient who died at 31 years, demonstrated "dedifferentiation" at 30 years. Low-grade fibromyxoid sarcoma is a distinctive, indolent soft-tissue sarcoma.

Desmoplastic fibroblastoma. A report of seven cases.

Seven cases of desmoplastic fibroblastoma, a distinctive fibrous soft-tissue tumor, are presented. The patients, four men and three women, ranged in age from 25 to 83 years (median 57 years). The tumors were located in the neck (two cases), the upper arm, the forearm, the shoulder, the lateral thigh, and the dorsum of the foot (one case each). Three neoplasms were intramuscular, and four were subcutaneous (two of the latter were directly on top of muscle). Maximum tumor dimension varied from 1.8 cm to 9 cm (median 3.2 cm). Grossly, the lesions were well circumscribed, firm, and white to gray to tan on cut section. Microscopically, they were composed of medium-sized to large "reactive appearing" spindled to stellate fibroblasts sparsely distributed in a fibromyxoid to densely fibrous background; mitotic figures were very rare or absent, tumor necrosis was not seen, and vascularity was low. The tumor border was generally well de-limited, although interdigitation with adjacent muscle or fat was present in areas in some cases. Follow-up ranging from 15 months to 46 months (median 28 months) after excision was available on five patients. No recurrences were observed.

Encapsulated columnar-cell neoplasms of the thyroid. A report of four cases suggesting a favorable prognosis.

Four encapsulated thyroid neoplasms with columnar-cell features were studied. The patients were a 29-year-old man and three women aged 42, 60, and 83 years. The tumors measured from 1.2 to 8.0 cm in maximum dimension. All were completely surrounded by a thick capsule; three demonstrated invasion into the capsule (but no farther), whereas one (from the 60-year-old woman) did not. In addition to columnar-cell areas, all the neoplasms had areas with follicular and solid growth, in varying proportions. Although the growth pattern in the columnar-cell zones was usually papillary, nuclear characteristics of papillary carcinoma were not present in these areas or elsewhere. Follow-up on the four patients was 112, 51, 112, and 29 months, respectively, and none had any evidence of recurrence or metastasis. The findings suggest that encapsulated columnar-cell thyroid tumors have a much more favorable prognosis than those that are unencapsulated and invasive into adjacent thyroid or extrathyroid tissue.

Smooth muscle in atypical lipomatous tumors. A report of three cases.

Three cases of atypical lipomatous tumor with areas of smooth muscle are presented. The patients were a 49-year-old man, a 45-year-old woman, and a 63-year-old man; their neoplasms were located in the spermatic cord, the mediastinum, and the retroperitoneum, respectively. The smooth muscle foci were well differentiated in all cases. Smooth muscle was present in the primary tumor in the first and second cases (spermatic cord and mediastinum) and in a recurrence in the second case (there has been no recurrence in the first case). In the third case (retroperitoneum), smooth muscle was found only in a recurrence; it was absent from later recurrences, which showed the features of dedifferentiated liposarcoma. The smooth muscle component did not appear to influence the behavior of the tumor in any case.

Dermatofibrosarcoma protuberans. A clinicopathologic review with emphasis on fibrosarcomatous areas.

We reviewed 75 cases of dermatofibrosarcoma protuberans (DFSP) from the University of Texas M.D. Anderson Cancer Center. All accessions were examined for areas of giant cell fibroblastoma (GCF), but none was found. The 30 cases having a minimum of 5 years follow-up were studied in more detail. The histologic findings were typical of DFSP in 24 cases, whereas in six cases discrete areas with a fascicular or "herringbone" growth pattern, considered to represent fibrosarcomatous change (DFSP-FS), were evident. The mitotic rate was usually but not always higher in fibrosarcomatous areas, and occasional examples of typical DFSP demonstrated relatively numerous mitotic figures (up to 35 per 10 high-power fields). Other histologic findings of interest were the presence of melanin in two cases of DFSP and the focal presence of a distinctive type of multinucleated giant cell similar to those seen in GCF in six cases. Patients with DFSP-FS differed from those with DFSP in that they had a higher median age (56 years vs. 37 years). Tumor location was similar in both groups, with the trunk being the most common site. No significant difference in either the rate of local recurrence or the interval until recurrence between DFSP and DFSP-FS was evident; the only factor strongly related to local recurrence was adequacy of surgical margins. However, the only two patients who died of tumor, including the sole patient with distant metastasis, had DFSP-FS. We conclude that DFSP-FS deserves recognition as a variant of DFSP.

Polymorphous low-grade adenocarcinoma: a study of 40 cases with long-term follow up and an evaluation of the importance of papillary areas.

Forty cases of polymorphous low-grade adenocarcinoma with a minimum of 10 years of follow up were reviewed. The patients included 13 men and 27 women age 22 to 71 years (median age, 54 years); 30 were white and 10 were black. The tumors were all intraoral, and the palate was the most common site (n = 24). Histologically, the neoplasms were characterized by nonencapsulated, infiltrative borders: bland, regular nuclei; and highly variable growth patterns, including tubular, solid, papillary, microcystic, cribriform (with true lumens), pseudoadenoid cystic (without true lumens), fascicular, single file, and strand-like. Papillary areas of more than focal extent were present in 17 cases, but these cases were otherwise similar to the remainder and were considered to form part of the spectrum of polymorphous low-grade adenocarcinoma. Thirteen patients had local recurrence, which was not controlled by subsequent treatment in six; six patients had cervical lymph node metastasis; three patients had distant metastasis; and five patients died of or with tumor after prolonged periods. There was a statistically significant relationship between more than focal papillary growth and cervical lymph node metastasis, and between positive or unknown surgical margins and local recurrence (although not uncontrolled local recurrence); however, these were the only independent statistically significant correlations found between any clinical or pathologic parameter and any aspect of tumor behavior or patient survival.

Follicular and Hurthle cell carcinomas of the thyroid: a comparative study.

University of Texas M. D. Anderson Cancer Center cases filed as Hurthle cell and follicular carcinoma were reviewed. Requirements for including a case in the study were that the diagnosis of Hurthle cell or follicular carcinoma be confirmed, that histologic material and clinical information be adequate, and that there be at least 9 years of follow-up. The study group included 18 cases of Hurthle cell carcinoma and 33 cases of follicular carcinoma. Ten of the Hurthle cell carcinomas had extrathyroid invasion, three had intrathyroid invasion, and five were encapsulated (i.e., they had intracapsular invasion only). In the follicular carcinoma group, 5 tumors had extrathyroid invasion, 14 had intrathyroid invasion, and 14 were encapsulated. When the cases were stratified according to extent of invasion in this manner, there was no statistically significant difference in rate of local recurrence, rate of metastasis (either regional lymph node or distant), or patient survival between Hurthle cell carcinoma and follicular carcinoma. Other variables including patient age and sex, treatment differences, tumor size, vascular invasion, predominant growth pattern (follicular versus solid-trabecular), nuclear size and pleomorphism, mitotic rate, and tumor necrosis did not provide significant additional prognostic information. Metastases of both Hurthle cell and follicular carcinoma were mostly distant and predominantly involved bone and lung. Behavioral differences between Hurthle cell and follicular carcinoma that were not statistically significant included a higher rate of local recurrence in Hurthle cell carcinoma with intrathyroid invasion, more frequent occurrence of regional lymph node metastasis in Hurthle cell carcinoma with extrathyroid invasion, and absence of distant metastasis and death caused by tumor in encapsulated Hurthle cell carcinoma. Five follicular carcinomas and one Hurthle cell carcinoma appeared to have arisen within an adenoma.

Metastasizing cellular dermatofibroma. A report of two cases.

Two cases of metastasizing cellular dermatofibroma (cutaneous fibrous histiocytoma) are presented. The first patient, an 18-year-old man, had a nodule excised from his right upper thigh. He developed three local recurrences at 1.5, 2, and 2.5 years and metastasis to inguinal lymph nodes. He underwent lung segmentectomies for metastases 1.5 and 4 years later and was alive with no evidence of tumor at latest follow-up, which was 15 months after the last surgery. The second patient, a 33-year-old man, had a nodule removed from his right posterior neck. The tumor recurred 3 months later and was reexcised. Right cervical lymph node metastases were excised at 7 and 8 years. A year later, a right cervical lymph node dissection yielded one positive node of 35, and multiple metastases were excised from the right lung. The patient was alive with lung metastases 6 years later, which was the latest follow-up. Grossly, both tumors were single 2 cm nonulcerated dermal-subcutaneous nodules. Histologically, they were characteristic of cellular dermatofibroma; they were composed of plump to spindled "fibrohistiocytic" cells arranged in a storiform pattern and had areas of hemorrhage, hemosiderin, and infiltration between dermal collagen bundles peripherally. Recurrences and metastases were histologically similar except that lung metastases were cystic. The alternative diagnosis of angiomatoid malignant fibrous histiocytoma was considered for these two cases but was excluded because the tumors were partly dermal, had a well-defined storiform pattern, and lacked large blood lakes, multinodularity, a fibrous pseudocapsule, and surrounding chronic inflammation. We conclude that dermatofibromas can rarely metastasize. Risk factors for metastasis may include relatively large size, high cellularity, and local recurrence. Judging from these two cases, metastasizing dermatofibromas behave in an indolent manner.

"Dedifferentiated" chordoma. A clinicopathologic and immunohistochemical study of three cases.

Three cases of "dedifferentiated" chordoma arising in the sacrococcygeal region are presented. In all three cases, the "dedifferentiated" component arose de novo in conjunction with conventional chordoma. Two of these patients, whose tumors had a prominent malignant fibrous histiocytoma (MFH) component, died within 6 months of diagnosis. Both patients had lung metastases, one of which was histologically documented to be MFH. The third patient, whose initial tumor contained osteosarcoma, died 76 months after diagnosis and multiple recurrences. Most notable in this case was the absence of the "dedifferentiated" component (in this instance, osteosarcoma) in all of the local recurrences as well as the lung metastases. These were composed exclusively of conventional chordoma. None of the patients had a previous history of radiation therapy. The immunohistochemical staining pattern of conventional chordoma was similar to that of previous reports, where the epithelial-like cells stained for cytokeratin and epithelial membrane antigen. In addition, they stained for alpha-1-anti-chymotrypsin and vimentin. These latter two markers were also identified in the "dedifferentiated" component. As with "dedifferentiated" chondrosarcomas and liposarcomas, "dedifferentiation" in a chordoma usually portends an accelerated clinical course.

Heterologous elements in the dedifferentiated component of dedifferentiated liposarcoma.

Five cases of dedifferentiated liposarcoma in which heterologous elements were present in the dedifferentiated component are presented. Two patients, men 54 and 66 years of age, had retroperitoneal atypical lipomatous tumors (well-differentiated liposarcomas) that recurred (after 2.5 and 12 years, respectively) as dedifferentiated liposarcomas with rhabdomyosarcomatous elements in the dedifferentiated components. The third patient, a 63-year-old woman, had a retroperitoneal dedifferentiated liposarcoma whose dedifferentiated component demonstrated focal osteoid formation. The fourth patient, a 36-year-old woman, had two seemingly separate retroperitoneal masses, one composed of atypical lipomatous tumor with foci of smooth muscle and the other of leiomyosarcoma; despite the apparent separation, it was thought more logical to consider this a dedifferentiated liposarcoma with leiomyosarcoma as the dedifferentiated component than two unrelated neoplasms. The fifth patient, a 45-year-old man, had a mediastinal dedifferentiated liposarcoma with angiosarcomatous areas in the dedifferentiated component. The relatively short follow-up thus far available on these cases has not demonstrated tumor behavior significantly different from that of dedifferentiated liposarcoma as a whole.

Behavioral assessment of visual toxicity.

A wide variety of behavioral methods has been employed with animals to assess visual changes induced by drugs or toxicants. The methods range from simple to complex, from broad screening devices to narrowly focused techniques. Their relative advantages for the environmental toxicologist are discussed. Manipulation of stimulus values is an essential ingredient in the identification of specific sensory functions. The percentage of correct choices from a discrete-trial, multiple-choice discrimination procedure is to be preferred to measures of response rate, speed or reaction time when experiments require answers about specific visual functions.

Utility of immunohistochemistry in bone marrow evaluation of T-lineage large granular lymphocyte leukemia.

Although T-lineage large granular lymphocyte (LGL) leukemia has been described for over 20 years, many patients with this neoplasm go unrecognized. Chief among the difficulties in diagnosing this entity is that the morphologic features are nonspecific and that it is difficult to distinguish it from reactive processes. The purpose of this study was to examine the histologic and immunophenotypic appearance of T-LGL leukemia in the peripheral blood and bone marrow, and to determine what features may suggest that ancillary studies such as flow cytometric and molecular analysis should be pursued to make a definitive diagnosis. We took a multidisciplinary approach by using morphology, immunoperoxidase staining, flow cytometric analysis, and molecular studies on 9 cases of T-lineage LGL leukemia. Our findings indicate that T-lineage LGL leukemia typically infiltrates the marrow diffusely. Most cases show a hypercellular marrow with an increase in myeloid precursors relative to the mature cells (i.e., an inversion of the myeloid maturation pyramid) and a decreased myeloid:erythroid ratio. Neutropenia without a left shift is usually seen in the peripheral blood. The tumor cells are usually CD3+, CD8+, CD57+, and TIA-1+. Most notably, the number of CD3+ T cells per high-power field is markedly elevated in T-LGL leukemia compared with normal, reactive, and pathologic marrows with neutropenia (mean values, 559 cells/mm(2) v. 7/mm(2), 11/mm(2), and 263/mm(2), respectively, P<.01). Moreover, CD57 staining also shows an increase in positive cells in T-LGL cases in comparison with normal, reactive, and pathologic marrows with neutropenia. Taken together, these findings indicate immunoperoxidase findings may be a useful tool to identify cases that should proceed to molecular or flow cytometric analysis.

Low-grade fibromyxoid sarcoma. A report of two metastasizing neoplasms having a deceptively benign appearance.

Two deceptively benign-appearing, unclassifiable but very similar fibromyxoid sarcomas characterized histologically by bland, innocuous-appearing fibroblastic cells and a swirling, whorled growth pattern are presented. The tumors both occurred in women in their late twenties and were located in the soft tissues of the scapular area and the axillary-chest wall area, respectively. Lung metastases developed in both cases; one patient died 94 months after excision of the primary neoplasm, whereas the other was alive at 82 months. The designation "low-grade fibromyxoid sarcoma" is suggested for these tumors.

Columnar-cell carcinoma of the thyroid. A report of two cases of an aggressive variant of thyroid carcinoma.

Two cases of thyroid-carcinoma characterized by tall columnar epithelium with marked nuclear stratification are presented. There were small foci exhibiting solid spindle-cell growth in both cases and a component demonstrating a microfollicular pattern in one. Both tumors were unencapsulated and invasive. Regional lymph node metastasis occurred in one case and distant metastasis in both, and both patients died of tumor within two years of initial thyroid surgery.

Mucoepidermoid carcinoma of salivary glands: a study of 69 cases with special attention to histologic grading.

Sixty-nine cases of mucoepidermoid carcinoma with a minimum of five years follow-up are presented. Major salivary glands were involved in 46 cases (44 parotid, two submandibular), and intraoral minor glands in 23. The tumor was considered histologically high grade (20 cases) when 90% or more of its area was made up of tumor cells and 10% or less of intracystic space and low grade (49 cases) when this ratio was lower. The proportion of cell types was not considered in grading: although intermediate, epidermoid, and clear cells usually predominated in high-grade tumors, several such examples contained numerous mucous cells. Grade was highly significant prognostically; all but 2 of the 14 deaths due to tumor and all six instances of distant metastasis occurred in cases with high-grade tumors. High histologic grade also was associated with an increased incidence of local recurrence (particularly recurrence not subsequently controlled) and cervical lymph node metastasis; in the case of recurrence this was due in part to the fact that inadequate surgical margins were more common with high-grade tumors. Tumors measuring less than 2.5 cm were rarely fatal regardless of grade, there being only two such deaths (one high grade, one low grade). Nuclear anisochromia and pleomorphism of more than slight degree, frequent mitoses, and tumor necrosis of more than focal extent were found to be untypical of mucoepidermoid carcinoma regardless of grade; these findings should occasion consideration of other diagnoses such as poorly differentiated adenocarcinoma with a solid growth pattern and adenosquamous carcinoma.

Adrenal cortical neoplasms. A study of 56 cases.

Fifty-six cases of adrenal cortical neoplasm with a minimum of 5 years follow-up are presented: 48 carcinomas and 8 adenomas. Adenomas typically had a maximal mitotic rate of fewer than 2 mitotic figures per 10 high-power fields (all cases), a prominent small nest growth pattern (7 cases), predominantly clear or foamy cytoplasm (6 cases), and no tumor necrosis (all cases), whereas carcinomas were characterized by at least 4 mitotic figures (often many more) per 10 high-power fields in the most active area (all cases), lack of a significant small nest growth pattern component (45 cases--solid or trabecular growth most common), at least a considerable proportion of cells with eosinophilic cytoplasm (all cases), and tumor necrosis (45 cases). Carcinomas were almost always larger than adenomas, but two adenomas (5.9 cm and 7 cm) overlapped in size with the four smallest carcinomas (5.5 cm, 6 cm, 7 cm, and 7 cm, respectively). The patients with adenomas were older on the average than those with carcinomas (median 58 years, range 31-71 years versus median 41 years, range 5 months-66 years). Two adenomas and 19 carcinomas were functional. No patient with adenoma had recurrence of tumor after excision, whereas all but nine carcinoma patients died of tumor, after 1 to 183 months. Among carcinoma patients, survival was significantly shorter when distant metastases were manifest at diagnosis (P = .0003). There was a trend toward shorter survival with higher mitotic rates and functional tumors, but neither these nor any other parameter had a statistically significant relationship to survival or tumor behavior when presence/absence of metastases at diagnosis was taken into account.

Carcinoma of the anal canal: a study of 79 cases.

Seventy-nine cases of carcinoma of the anal canal treated initially by surgery and having a minimum follow-up of five years were reviewed. It was found that all of the tumors were basically squamous cell carcinomas. They were divided into five histologic categories: keratinizing squamous cell carcinoma (52 cases), nonkeratinizing squamous cell carcinoma (6 cases), basaloid squamous cell carcinoma (11 cases), squamous cell carcinoma with mucous microcysts (6 cases), and pseudoadenoid cystic squamous cell carcinoma (4 cases). There was considerable overlap among the categories. The neoplasms also were stratified according to depth of invasion: 4 into submucosa only, 30 into smooth muscle of the anal sphincter, and 45 into perianal tissue. There were no significant differences in survival among the histologic categories but marked differences relating to depth of invasion: none of the 4 patients with submucosal invasion died of tumor, whereas 8 of the 30 with smooth muscle invasion and 35 of the 45 with perianal tissue invasion did so. The histologic categories also did not differ significantly in regard to the rates of lymph node metastasis (either at the time of initial surgery or later) or local recurrence; however, the rate of distant metastasis was higher in pseudoadenoid cystic squamous cell carcinoma (three of four cases) than in the other categories (11 of 75 cases combined). Based on our pathologic and clinical findings, we believe that there is no entity "cloacogenic carcinoma," "transitional cell carcinoma," "basaloid carcinoma," or "mucoepidermoid carcinoma" in the anal canal separable from squamous cell carcinoma, and we therefore suggest that these terms be dropped (or restricted to appropriate tumors in other locations). Pseudoadenoid cystic squamous cell carcinoma was the most distinctive of our histologic categories and is deserving of further study.