James S. A. Neill

Age‐linked prognostic categorization based on a new histologic grading system of neuroblastomas. A clinicopathologic study of 211 cases from the pediatric oncology group

Histologic sections (minimum of four sections per patient) from 211 patients with neuroblastoma were reviewed. The tumors were resected before therapy, which was standardized according to age and stage. Low mitotic rate (MR) (≤ ten per ten high‐power fields) and calcification emerged as the most significant prognostic features after statistical analysis by stepwise log‐rank tests (P < 0. 0001 and P = 0. 0065, respectively). Histologic Grades 1, 2, and 3 were defined on the basis of the presence of both, any one, or none of these two prognostic features, respectively (Grade 3 had absence of low MR, i.e., these tumors had high MR [> ten per ten high‐power fields]). Statistically significant differences in survival were observed in the grades after adjusting for age and stage (P < 0. 001). The degree of differentiation, although significant by itself, was no longer significant after adjusting for the grades, Age groups (≤ 1 versus > 1 year of age), which also emerged as an independent prognostic feature (P < 0. 001), were linked with the grades to define two risk groups as follows: (1) a low‐risk (LR) group consisting of patients in both age groups with Grade 1 tumors and patients 1 year of age or younger with Grade 2 tumors and (2) a high‐risk (HR) group consisting of patients older than 1 year of age with Grade 2 tumors and patients in both age groups with Grade 3 tumors. The difference in survival between LR (160 cases) and HR groups (51 cases) was statistically significant (P < 0. 001). Concordance between these LR and HR groups and the Shimada classification was observed in 84% of cases. The new histologic grading system has the following advantages: (1) use of familiar terminology and histologic features in the grading system and (2) relative ease of assessment because the degree of differentiation does not need to be determined. The grading system should be tested on a new data set with an appropriate histologic sample of similar size to confirm these results.

Recommendations for modification of terminology of neuroblastic tumors and prognostic significance of Shimada classification. A clinicopathologic study of 213 cases from the Pediatric Oncology Group.

To develop consistency in terminology and pathologic criteria, the authors reviewed the literature and 213 cases of neuroblastic tumors (NT) registered with Pediatric Oncology Group (POG) protocols 8104 and 8441. The patients were given standardized therapy stratified according to POG stage and patient age, and four or more histologic sections of primary tumor resected before therapy were available in each of these 213 cases. All stages were represented. The recommended nomenclature combines conventional terms and criteria with those used by Bove and McAdams and Shimada et al. The main features of the recommended nomenclature are as follows: (1) the terms neuroblastoma (NB) and ganglioneuroblastoma (GNB) are retained instead of stroma‐poor NB and stroma‐rich NB, recommended by Shimada et al.; (2) undifferentiated NB is considered a subtype separate from poorly differentiated NB; and (3) the term GNB is used only when there is a predominant ganglioneuromatous component admixed with the minor neuroblastomatous component. With the use of these criteria and terms, the Shimada classification was determined in the 213 cases. The results showed that, even after stratification for age, POG stage, and primary site, there is a statistically significant difference in survival rate between favorable histologic and unfavorable histologic prognostic subgroups. The authors recommend that definitive prognostic categorization of an NT according to Shimada classification should be done only when adequate histologic material is available from a primary tumor resected before any other therapy. Categorization done on histologic material from small biopsy specimens, previously treated primary tumors, or meta‐static sites should be considered tentative.

Metastatic Minimally Invasive (Encapsulated) Follicular and Hurthle Cell Thyroid Carcinoma: A Study of 34 Patients

Most studies that have examined minimally invasive, encapsulated, follicular carcinoma (FC) or Hurthle cell carcinomas (HCs) have contained only a few metastatic neoplasms. We studied 34 patients with a single, minimally invasive, metastatic FC or HC and compared them with 38 patients with similar, nonmetastatic FCs or HCs. The numbers of incomplete capsular penetration (neoplasm into but not through the capsule), complete capsular penetration (neoplasm through the capsule), and vascular invasion foci were quantified. The median number (three), range, and distribution of complete capsular penetration and vascular invasion foci were similar in the nonmetastatic and metastatic carcinomas. All of the metastatic FCs and HCs had at least one vascular invasion or complete capsular penetration focus. Sixty-two percent of the metastatic carcinomas had two to four complete capsular penetration foci, and 60% had two to four vascular invasion foci. Two metastatic neoplasms had incomplete capsular penetration but had one and two vascular invasion foci, respectively. One tumor had no vascular invasion but had four complete capsular penetration foci. No metastatic neoplasms had incomplete capsular penetration only. There were no differences in the number of vascular invasion or complete capsular penetration foci between metastatic and nonmetastatic FCs and HCs and between metastatic FCs and HCs. Most metastatic neoplasms had vascular space invasion and complete capsular penetration. The number of complete capsular penetration or vascular invasion foci was not associated with the initial site of metastasis or the interval between the surgery and the metastasis.

Systematization of primary histopathologic and fine-needle aspiration cytologic features and description of unusual histopathologic features of neuroblastic tumors: A report from the pediatric oncology group

On the basis of a detailed review of the primary histopathologic features of 239 cases and the fine-needle aspiration cytologic features of seven cases, a systematized schema of differentiation, progressive maturation and organization, and biologic behavior in neuroblastic tumors (NTs) is presented. The differentiation is of the gangliocytic and schwannian lineages. Maturation occurs in differentiating neuroblasts, leading to the formation of various stages of ganglion cells and Schwann cells. Organization is characterized by nesting pattern, rosette formation, parallel arrangement of neuropil, and alignment of Schwann cells along the neurites. According to this schema the NTs can be arranged in the following order: undifferentiated, poorly differentiated, and differentiating neuroblastoma; nodular, intermixed, and borderline ganglioneuroblastoma; and ganglioneuroma. Formulation of such a schema is helpful in gaining a better understanding of the complex pathologic features and in defining the criteria for various types of NTs. Therefore, the schema also would be helpful in achieving uniformity and reproducibility of the diagnosis of various types of NTs. Previously unreported features related to shape, size, nucleus, and cytoplasm of neuroblasts; secondary changes and patterns; changes in the fibrovascular septa; and other morphologic aspects of NTs and features (such as large tumor cells, karyorrhectic cells in fine-needle aspiration biopsy, tumor giant cells, anaplasia, and nesting pattern of tumor cells that have not been sufficiently emphasized) also are described. The importance of these previously unreported and insufficiently emphasized features relates to the histologic and cytologic diagnosis of NTs. For example, some of the features, such as starry sky appearance and spindle-shaped neuroblasts, may be misleading if seen in a small biopsy specimen. Others, such as tumor giant cells resembling ganglion cells and nesting pattern, will provide clues to the correct diagnosis. Some of the features, such as sclerosing pattern, hyalinization, and dense lymphoplasmacytic infiltration, may be related to the phenomenon of regression exhibited by neuroblastomas.

A Steroid-Responsive Nephrotic Syndrome in a Patient with Human Immunodeficiency Virus (HIV) Infection

Patients with human immunodeficiency virus (HIV) seropositivity may present with various renal abnormalities, including minimal, focal, or diffuse glomerular mesangial proliferation (1-3). In addit...

Apocrine nevus: light microscopic, immunohistochemical and ultrastructural studies of a case

The apocrine nevus (AN) is a rare tumor occurring in the upper chest and the axilla. We report a case of a AN in a 33‐year‐old female occurring unilaterally. The presenting complaint related to tenderness and swelling in the right axilla. The initial impression was hidradenitis suppurativa. The gross specimen revealed the presence of irregular thickening just beneath the dermal subcutaneous interface. Microscopically the lesion was composed of mature apocrine glands with apical snouts. The glands were arranged in lobules divided by thin fibrous septa. immunohistochemical studies revealed the following profile in the glandular epithelium: positive low molecular weight cytokeratin, epithelial membrane antigen, and gross cystic disease fluid protein reactivity and negative high molecular cytokeratin and S‐100 protein reactivity. Carcinoembryonic antigen reactivity was found in the duet epithelium. Ultrastructural studies revealed cells lining the lumen of the glands with a concentration of granules in the apical region and light and dark granules. These findings support the previously described light microscopic observations and provide unreported ultrastructural studies in this rare tumor.

The Effect of Electrothermal Cautery-Assisted Resection of Diminutive Colonic Polyps on Histopathologic Diagnosis

We examined diminutive colonic polyps to identify relationships between thermal electrocoagulation or resection trauma cytologic artifacts, type of thermal electrocoagulation, polyp size, and the interobserver variation among 3 pathologists. The 3 pathologists independently evaluated 119 colonic polyps 5 mm or less in maximum dimension for diagnosis and degree of thermal electrocoagulation or resection trauma cytologic artifacts. The maximum dimension of the polyps and type of thermal electrocoagulation were recorded. The average percentage of polyps in which a definitive diagnosis could not be made because of cytologic artifacts was 16.5% (range, 11.8%-19.3%). Decreasing polyp size was associated linearly with the inability to make a definitive diagnosis owing to cytologic artifacts. Polyps smaller than 2 mm significantly more often could not be definitively diagnosed by at least 1 pathologist owing to cytologic artifacts, including some polyps that were excised without thermal electrocautery. Interobserver variation increased with decreasing polyp dimension. Two millimeters seems to represent a cut point, below which the likelihood that a definitive diagnosis can be made can be increased if thermal electrocoagulation is used. This small size seems to make them especially susceptible to cytologically injurious forces.

Utilizing biologic assimilation of bovine fetal collagen in staged skin grafting.

Seven patients underwent 2-stage skin grafting with bovine fetal collagen (BFC) as an initial wound cover. Split-thickness skin grafts were successfully placed on the wounds after completion of interval management. BFC proved to be a resilient acellular dermal matrix that could proceed to assimilation and skin grafting under a variety of wound conditions. BFC may prove to be a valuable material, as the role of acellular dermal matrices in skin grafting becomes better defined.

Tissue Response to Bovine Fetal Collagen Extracellular Matrix in Full-Thickness Skin Wounds

OBJECTIVES To present the findings of the biological response and assimilation of bovine fetal collagen (BFC) as observed in biopsy specimens taken after implant. METHODS The biopsy specimens were from 9 patients with full-thickness skin wounds who received the BFC biomaterial in the first stage of a 2-stage reconstruction. Biopsy specimens were taken at the second stage of skin grafting from the wound margins. RESULTS The response to the BFC included neovascularization and infiltration of the collagen matrix with fibroblasts. The acellular matrix had the tinctural properties of devitalized tissue, which may be mistaken for coagulative necrosis if one is unaware of the biomaterial implant. CONCLUSIONS The characteristics of BFC histology should be recognized by pathologists involved in patients treated for reconstruction and wound care.