Patterns of stromal invasion in ovarian serous tumors of low malignant potential
Causes of death, as determined by autopsy, in previously healthy or near-healthy children
Occurrence of a double-positive T-cell population in nodular lymphocyte predominant Hodgkin lymphoma
Stromal-epithelial patterns of invasion in serous tumors of the ovary have been subclassified as destructive and nondestructive. By definition, well-differentiated serous tumors featuring destructive stromal invasion are classified as low-grade serous carcinomas, whereas those with no stromal invasion or stromal microinvasion are classified as serous tumors of low malignant potential (S-LMP). The histologic features of stromal microinvasion in ovarian S-LMP have been addressed in a variety of studies, but controversy persists regarding diagnostic criteria and prognostic significance, particularly in patients with high-stage disease. In addition, a subset of otherwise typical S-LMP has patterns of invasion that are not classic destructive invasion and do not meet the diagnostic criteria for stromal microinvasion because of qualitative features or size restrictions. To further evaluate the full histologic spectrum of stromal-epithelial patterns of invasion in otherwise typical S-LMP, the authors examined a series of 60 ovarian S-LMP (34 FIGO stage I; 26 FIGO stages II, III, and IV) with stromal-epithelial alterations that do not meet the criteria for classic destructive invasion. This group of cases included those defined as microinvasion and a subset that would be excluded based on size measurements or unusual qualitative features but that did not exhibit significant stromal reaction. Five patterns of invasion were identified: individual eosinophilic cells and cell clusters, cribriform, simple and noncomplex branching papillae, inverted macropapillae, and micropapillae. Individual, discrete aggregates of invasive epithelium ranged from 1 to 12 mm (mean, 1.4 mm) in greatest linear dimension as measured by conventional methods. The number of discrete foci ranged from one to more than 10; in seven tumors (12%), the invasive foci were diffusely scattered throughout the stroma without discrete aggregates. These stromal-epithelial alterations were associated with disease progression or death due to disease, or both, in nine of 50 (18%) patients with followup (mean, 92.5 months). They were also co-variant with other adverse prognostic features, including invasive implants, nodular lymph node aggregates, high stage, and unresectable disease. Disease progression was most strongly linked to the presence of micropapillae, but the majority of patients with an adverse outcome had the more common, classic stromal-epithelial patterns associated with microinvasion—that is, individual cells, cell clusters, and simple papillae. Neither size of the largest contiguous aggregate nor extent of stromal involvement correlated with outcome. Classic microinvasion disproportionately occurred in patients presenting during pregnancy (P<0.0001) and was not associated with adverse outcome in that setting, but followup was limited. Based on cumulative outcome data, the presence of stromal-epithelial patterns of invasion distinct from classic destructive invasion in otherwise typical S-LMP stratified patients at long-term risk for disease progression. However, it does not warrant a diagnosis of carcinoma or a change in management schemes. Maintaining classification as a S-LMP (serous borderline tumor) with stromal invasion seems appropriate, even in the presence of diffuse stromal involvement or discrete aggregates measuring greater than 3 mm or 5 mm. The authors concluded that the stromal-epithelial alteration featuring micropapillae may represent a comparatively higher risk lesion with a clinical course analogous to that of low-grade serous carcinoma. Therefore, pathologists should identify this specific stromal-epithelial pattern in the diagnostic report until there are sufficient data to form more definitive conclusions regarding prognosis.
McKenney JK, Balzer BL, Longacre TA. Patterns of stromal invasion in ovarian serous tumors of low malignant potential (borderline tumors): a re-evaluation of the concept of stromal microinvasion. Am J Surg Pathol. 2006;30:1209–1221.
Reprints: Dr. Teri A. Longacre, Dept. of Pathology, Stanford University School of Medicine, Room L235, 300 Pasteur Drive, Stanford, CA 94305; email@example.com
The diseases responsible for the nontraumatic deaths of previously healthy children cannot be determined from mortality statistics because such statistics may reflect deaths from chronic disease. The authors conducted a study to identify causes of nontraumatic death in previously healthy or near-healthy children presenting to a children’s hospital. They retrospectively reviewed autopsy protocols from 572 children who died at Children’s Hospital of New Orleans between 1985 and 2003. They adhered to the premise that autopsy was performed after most deaths of previously healthy or near-healthy children. Causes of death were grouped by disease processes and age groups and were compared to premortem clinical diagnoses. Eighty-eight autopsy protocols were from children who were previously healthy or near healthy before the hospital admission during which they died. The median age was 11.4 months, and the median length of stay was two days. Infection, primarily of the central nervous system and systemic (septicemia), was the most common cause of death (53%, 47 cases). Neoplasia, primarily of the central nervous and hematologic systems, was the second most common cause (15%, 13 cases). The predominant organ system involved with disease was the nervous system (36%, 32 cases). Unrecognized congenital disorders were found in approximately 10 percent of the cases. The authors concluded that infectious diseases are a frequent cause of death in previously healthy children, and that fatal diseases most frequently affect the nervous system. Autopsy provides valuable information in the death of healthy children.
Taggart MW, Craver R. Causes of death, determined by autopsy, in previously healthy (or near-healthy) children presenting to a children’s hospital. Arch Pathol Lab Med. 2006;130:1780–1785.
Reprints: Dr. Randall Craver, Dept. of Pathology, Children’s Hospital of New Orleans, 200 Henry Clay Ave., New Orleans, LA 70118; firstname.lastname@example.org
Nodular lymphocyte predominant Hodgkin lymphoma is a distinct subtype of Hodgkin lymphoma for which T-cell subsets have not been studied specifically. The authors reviewed 24 cases of nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) and compared flow cytometric results with those of 13 progressively transformed germinal centers (PTGC) cases, 78 nonspecific reactive hyperplasia cases, and 31 classical Hodgkin lymphoma cases. A double-positive (CD4+CD8+) T-cell population was present in 58 percent of NLPHL cases, constituting 10 percent to 38 percent of T cells. The cells were CD3+, CD5+, CD2+, CD7+, CD1a–, and terminal deoxynucleotidyl transferase–. Similar CD4+CD8+ T cells were identified in 38 percent of PTGC cases (P=0.31), four percent of reactive hyperplasia specimens (P<0.00001), and six percent of classical Hodgkin lymphoma specimens (P<0.0001). The authors concluded that the presence of a CD4+CD8+ T-cell population in NLPHL may reflect an activated or reactive T-cell subset and should not lead to a misdiagnosis of T-cell lymphoma. This population may be a clue to the diagnosis of NLPHL, particularly in cases with limited tissue.
Rahemtullah A, Reichard KK, Preffer FI, et al. A double-positive CD4+CD8+ T-cell population is commonly found in nodular lymphocyte predominant Hodgkin lymphoma. Am J Clin Pathol. 2006;126:805–814.
Reprints: Dr. A. Rahemtullah, Dept. of Pathology, WRN 219, Massachusetts General Hospital, 55 Fruit St., Boston, MA 02114
Dr. Cibull is professor of pathology and laboratory medicine and direct of surgical pathology, University of Kentucky Medical Center, Lexington. Dr. Kesler is hematopathology fellow, University of Texas Southwestern Medical Center at Dallas.