Lymphatic endothelial cancerization in papillary thyroid carcinoma: hidden evidence of lymphatic invasion.

We hypothesize that cystic structures in metastatic papillary thyroid carcinoma (PTC) develop along the framework of lymphatic channels. To investigate this phenomenon, different categories of PTC were immunostained for D2-40 and TTF1. In this study, reactivity for D2-40 was considered as positive when there is membranous staining as often seen in lymphatic endothelial cells. Thirty cases of PTC with lymph node metastasis or with potential for lymphatic invasion and 20 cases metastatic PTC in lymph nodes were reviewed and found to show double/mosaic immunoreactivity for TTF1/D2-40 in 40-100% of cases. PTC metastasis in lymph nodes with cysts and some branching lymphatic-like channels lined by follicular cells with or without nuclear features of PTC were diffusely reactive to TTF1, and focally to D2-40. For primary and metastatic PTC, focal membranous D2-40 reactivity was also demonstrated in cysts or cleft linings. For25 thyroid neoplasms with no known potential for lymphatic invasion, there was no such immunoreactivity. The mosaic or double immunoreactivity for TTF1/D2-40 suggests lymphatic cancerization and possible endothelial mimicry of follicular cells. Mosaic/double immunoreactivity is helpful to detect the hidden pattern of lymphatic invasion masquerading as 'benign-appearing' follicles and supports our hypothesis of malignant cells developing along the lymphatic framework.

Histopathogenesis of non-HPV-related differentiated oral squamous intraepithelial neoplasia.

INTRODUCTION: A study of immunohistopathologic and cytohistopathologic changes of the parabasal/basal layers in the differentiated squamous intraepithelial neoplasia (DSIN) may elucidate the histopathogenesis and reveal changes aiding early diagnosis and grading of the lesion. MATERIALS AND METHODS: A total of 55 consecutive resection specimens of nonbasaloid squamous cell carcinoma of the anterior oral cavity and 8 biopsies before resections displaying DSIN in the overlying squamous epithelium were examined. RESULTS: Squamous epithelium that is continuous/immediately adjacent to invasive squamous cell carcinoma (type 1) and the more peripheral (type 2) epithelium of resection specimens displayed consistent changes in the parabasal/basal layers: (A) cytologic atypia with proliferation of parabasal cells with downward expansion causing reactive proliferation of the basal cell layer in the early stage, invading the basal layer in the late stage; (B) disordered nuclear/cytoplasmic arrangement; (C) "Cobblestone" appearance. Immunoreactivity for TP53 and Ki67 was helpful in the diagnosis. The epithelial spectrum of changes decreased as one moved from type 1 to type 2 lesions. Five out of 8 biopsies showed type 1 lesions (followed by resection in a period of 11±6 mo) and 3 showed type 2 lesions (followed by resection in a period of 55±20 mo). In addition, resections were margin positive for type 2 lesions in 5 cases associated with recurrence at the site of resection during a period of 69±9 months. CONCLUSIONS: DSIN is characterized by a proliferation of neoplastic parabasal cells with dyskeratosis, downward expansion/pushing of the basal layer with elongation of rete ridges. We proposed grading of DSIN based on the changes of the parabasal/basal layers.

Topographic Distribution of Papillary Thyroid Carcinoma by Mapping in Coronal Sections of 125 Consecutive Thyroidectomy Specimens.

INTRODUCTION: Mapping of different foci in multifocal papillary thyroid carcinoma (PTC) has previously not been done as it is difficult to do so when thyroid specimens are serially sectioned transversely (ie, parallel to the horizontal plane). In this study, thyroidectomy specimens were serially sectioned coronally (ie, parallel to the largest surface of the thyroid gland), which allows for panoramic and 3-dimensional visualization of PTC foci and their relationship to one another. MATERIALS AND METHODS: A total of 125 consecutive total thyroidectomies or lobectomies followed by completion thyroidectomies were serially sectioned coronally and reviewed with identification and characterization of PTC foci. PTCs were grouped into either discrete, encapsulated nodule(s) (EN) of both follicular or papillary architecture, usual variant (UV), or tall cell variant (TCV). RESULTS: The predominant tumor masses were identified in the right lobe, isthmus, and left lobe in 52%, 8%, and 40%, respectively. The largest tumor nodules ranged from 3 to 60 mm (18.8 ± 6.6) with the UV, EN, and TCV groups accounting for 58%, 24%, and 18% of cases, respectively. Three topographic patterns of PTC can be distinguished as follows: (a) single tumor nodule (37 cases), (b) main tumor nodule with satellite nodule(s) displaying no or varying degrees of fusion with the main one (30 cases), and (c) main tumor nodule with either a second large nodule or randomly occurring tumor nodules (58 cases). Bilaterality can be seen in all 3 patterns but was most prevalent in the group comprising the main tumor nodule with either a second large nodule or random tumor nodules. It was least frequent in the EN group without random tumor nodules. The difference in rates of bilaterality between tumors <10 mm and ≥10 mm was statistically significant (P < .01). For all 3 groups, satellite nodules displayed histopathological features that were similar or dissimilar to the main tumor mass. They may be of a different variant than that of the main tumor nodule. CONCLUSIONS: With panaromic and 3-dimensional visualization, individual tumors/satellite or random nodules of multifocal PTC were readily identified in serial coronal sections of thyroidectomy specimens. Bilaterality was frequently observed in tumors associated with random PTC foci, whereas, the EN group tended to be unilateral and was not associated with random foci.

Hemolytic transfusion reactions after administration of intravenous immune (gamma) globulin: a case series analysis.

BACKGROUND: This case series summarizes our observations of hemolytic reactions after the administration of large amounts of intravenous immune (gamma) globulin (IVIG). STUDY DESIGN AND METHODS: Cases of hemolysis were identified by a decrease in hemoglobin not otherwise explained following IVIG administration. RESULTS: Sixteen cases were identified over a 2 1/2-year period at the Ottawa Hospital of approximately 1000 patients receiving IVIG (1.6%). Characteristics of these patients include a large dose of IVIG, female sex, non-O blood group, and underlying inflammatory state. CONCLUSIONS: Significant hemolysis may occur after the administration of large doses of IVIG. A two-step mechanism of hemolysis is proposed, sensitization by ABO isohemagglutinins followed by phagocytosis by activated macrophages. A simple protocol to facilitate the early detection of such cases is presented.

A pilot trial evaluating the clinical effects of prolonged storage of red cells.

The clinical consequences of prolonged storage of red cells have not been established. In this pilot study, we evaluated whether it would be feasible to provide a continuous supply of red cells stored <8 days. In addition, we examined the potential benefits attributed to "fresh" as compared to standard red cells in 66 critically ill and cardiac surgical patients. Nine patients were issued red cells but were not transfused. From the 57 remaining patients, the number of units transfused averaged 5.5 +/- 8.43 red cell units in the experimental group compared to 3.3 +/- 3.27 red cell units in the standard group (P = 0.25). The median storage time was 4 days in the experimental group compared to 19 days in the standard group (difference of 15 days; interquartile range of 12-16 days; P < 0.001). Overall, 73% of patients received red cells with storage times that corresponded to the treatment allocation more than 90% of the time. The group receiving red cells <8 days old tended to be older on average (68 +/- 8.54 yr versus 63 +/- 15.30 yr; P = 0.13) and have more comorbid illnesses (85% versus 65%; P = 0.09). In total, 27% of patients in the experimental group died or had a life-threatening complication as compared to 13% in the standard group (P = 0.31). There were no differences in prolonged respiratory, cardiovascular, or renal support after randomization (P > 0.05). A large clinical trial comparing red cell storage times is feasible and warranted given the limited available evidence.