Autopsy Standardized Mortality Review: A Pilot Study Offering a Methodology for Improved Patient Outcomes.

A standardized mortality review of hospital autopsies identified discrepancies between clinical diagnoses and autopsy findings, unexpected deaths, adequacy of diagnostic workup, presence of adverse event, and type of a quality issue if present. The standardized review elements were chosen based on a review of quality metrics commonly used by hospitals. The review was completed by the pathologist based on their initial autopsy findings. The final autopsy report was later reviewed to confirm the initial review findings. Major discrepancies in diagnosis were categorized as class I or II based on the modified Goldman criteria. Ninety-six hospital autopsy cases from January 2015 to February 2018 were included in the study. The overall major discrepancy rate was 27%. Class I discrepancies, where a diagnosis found at autopsy might have improved survival had it been made premortem, were identified in 16% of cases. Categories associated with increased discrepancy rates included unexpected deaths, inadequate workup, abnormal labs or imaging not addressed, and certain quality issues. Deaths not expected at admission but expected at the time of death, those with adverse events, those within 48 hours of a procedure, those within 48 hours of admission, those with physician-specific quality issues, and those with system or process issues were not significantly related to diagnostic accuracy.

The microbiology laboratory's role in life-threatening infections.

The microbiology laboratory's contribution to the care of patients who are critically ill is explored. The economic and epidemiologic impact of broad-spectrum antibiotic use is discussed, along with methodology of antimicrobial susceptibility testing and the potential value of an antibiogram. The clinical benefits of blood, sputum, urine, spinal fluid, and wound cultures are discussed, with an emphasis on interpretation of culture results. The significance of, and procedures for, proper specimen collection are emphasized throughout the article, and the ramifications of improper specimen collection are presented.

Clinical, radiographic, and pathologic features of medical calcific sclerosis in the breast.

Medial calcific sclerosis (MCS), a nonocclusive calcification of the media of small to medium-sized muscular arteries, may occur in the breast. To ascertain whether MCS causes difficulty with mammographic interpretation of breast calcifications and to determine its clinical and pathologic associations, we reviewed the records and biopsy specimens from 62 patients who had had screening mammography and breast biopsy, lumpectomy, or mastectomy. Ten specimens from 7 patients showed MCS. Average age of patients without MCS was 48.8 years, and that of the 7 patients with MCS was 61.3 years. Microcalcifications were found in 25 of 62 mammograms (34%). Of the 7 patients with MCS, 2 had hypertension, 1 diabetes mellitus, 2 diabetes mellitus and hypertension, and 2 neither hypertension nor diabetes mellitus. In 5 specimens, calcification only was associated with MCS. In 2 of these specimens, the mammographic calcifications were thought to be suggestive of malignancy on the basis of clustering and spiculation. One of the 2 was benign on histopathology; the other was malignant. Overall, carcinoma was identified in 3 of 7 patients with MCS (compared with 11 of 55 patients without MCS) and in 2 of 5 specimens (2 patients) with mammary MCS as the only type of calcification. The mammographic appearance of the microcalcification in MCS may suggest malignancy.

Fine-needle aspiration of well differentiated small-cell duct carcinoma of the breast.

Historically, fine-needle aspiration of the female breast has been accepted as a useful modality in the diagnosis of ductal as well as other types of breast carcinoma. However, cases of well differentiated small-cell duct carcinoma can be problematic. The differential diagnoses include fibrocystic disease, papillary neoplasia, fibroadenoma, and lobular carcinoma. Retrospectively, 16 cases of well differentiated small-cell duct carcinoma have been identified in the case files of Truman Medical Center/University of Missouri-Kansas City. Patient's ages ranged from 29-81 yr, with the mean being 56.2 yr. The overall cytologic features consisted predominantly of a hypercellular specimen with cohesive and rarely discohesive cells with no demonstrable nuclear atypia. For well differentiated small-cell duct carcinoma, the mean nuclear diameter was greater than that of a red cell (6-8 microns). For the well differentiated small-cell duct carcinoma group, the mean nuclear diameter was 9.86 microns; for fibrocystic disease, 12.86 microns; for papillomas, 8.28 microns; for fibroadenomas, 9.48 microns; and for lobular carcinoma, 11.88 microns. From our data, it appears that specific attention to the clinical presentation, cytologic pattern, and nuclear diameters are useful discriminators for well differentiated small-cell duct carcinoma.

Malignant thymoma in a patient with HIV positivity: a case report with a review of the differential cytologic diagnoses.

A 33-yr-old African-American male with known human immunodeficiency virus (HIV) positivity underwent CT guided fine-needle aspiration biopsy of an anterior mediastinal mass. The aspirate was composed of a dimorphic population of cells that included small mature lymphoid cells and scattered cohesive groups of large epithelial cells in equal numbers. The neoplasm stained strongly for low weight molecular cytokeratin, epithelial membrane antigen (EMA), leukocyte common antigen (LCA), and Leu-7 which was consistent with a diagnosis of thymoma. Subsequent biopsies determined the neoplasm to be a malignant (invasive) thymoma. This case emphasizes the efficacy of FNA biopsy for the evaluation of anterior mediastinal masses in HIV infected individuals. Additionally, the differential cytologic diagnoses for HIV infected individuals for this anatomic site are discussed.

Clinical and experimental evidence of inhibition of testosterone production by suramin.

The effect of suramin on testosterone production was evaluated in cancer patients, adult male rats, rat Leydig cells, and NCI-H295 human adrenal cancer cells. Testosterone plasma levels markedly decreased in 14 patients receiving suramin as a therapy for refractory cancer, and in 8 of them, the plasma LH and/or FSH levels increased beyond the normal range. The hCG stimulation test (5000 IU, im) was performed in 8 patients and induced an average 2.1-fold increase in testosterone levels over baseline values. Testicular histology after suramin treatment was available in 1 patient who died of progressive disease; this revealed atrophy of seminiferous tubules and reduced Leydig cells in the interstitium. A significant reduction in plasma testosterone was also observed in rats given 18 mg/kg suramin, ip, twice weekly for 8 weeks, whereas plasma LH and FSH levels did not change significantly. Cytohistochemistry of testes from suramin-treated rats showed a reduced number of 3 beta-hydroxysteroid dehydrogenase-positive cells within the interstitium compared to controls, and light microscopy revealed severe impairment of spermatogenesis. Suramin inhibited the production of testosterone by isolated rat Leydig cells as well as the conversion of pregnenolone to progesterone by the 3 beta-hydroxysteroid dehydrogenase enzyme extracted from rat testes, with 50% inhibitory concentrations (IC50 values) of 108.2 and 87.5 micrograms/mL, respectively. Furthermore, suramin reduced the release of testosterone into the culture medium of NCI-H295 adrenal cancer cells with IC50 values of 91.2 and 83.9 micrograms/mL after 6 and 12 days, respectively. These data provide the first evidence in patients that suramin treatment produces a marked reduction in the circulating levels of testosterone, a result that was also obtained in experimental models.

Tumoral fibrosis and lack of circumscription in granular cell tumor of the breast.

Granular cell tumors are benign neoplasms of putative Schwann cell origin that most commonly occur in the tongue. While granular cell tumors in the breast are uncommon, the occurrence of this tumor at this site warrants special consideration, since the mammographic, gross, and microscopic appearance can mimic carcinoma. We describe the case of a 61-year-old white woman with a granular cell tumor of the left breast. Our case and a review of the international literature show that desmoplasia and lack of circumscription are common features of granular cell tumor of the breast.

Amyloid in adrenal gland pheochromocytomas.

OBJECTIVE: To assess the frequency of amyloid deposits in adrenal gland pheochromocytomas. DESIGN: We evaluated 22 pheochromocytomas using routine hematoxylin-eosin and Congo red stains, polarization microscopy, and electron microscopy. Cases with amyloid were further characterized immunohistochemically. RESULTS: Congo red and polarization microscopy revealed characteristic apple-green birefringence, not abolished by potassium permanganate incubation, in only one neoplasm. In a subset of the remaining tumors, yellow or yellow-green birefringence not characteristic of amyloid was found. We performed electron microscopy on the tumor with characteristic apple-green birefringence and six other neoplasms with abundant yellow or yellow-green birefringence. Amyloid was identified in two tumors, including the Congo red-positive tumor, while the remaining five neoplasms contained collagen. Immunohistochemically, the amyloid deposits were reactive with component P and immunoglobulin kappa- and lambda-light chains in both tumors. Adsorption studies using human urine with monoclonal immunoglobulin kappa- or lambda-light chains abolished reactivity, consistent with specific immunostaining for both light chains. Transthyretin was present in one tumor. The neoplastic cells expressed chromogranin, neuron-specific enolase, and [Leu5]-enkephalin, although the amyloid was not reactive. CONCLUSIONS: We conclude that amyloid is infrequent in pheochromocytomas. Electron microscopic examination is more sensitive than Congo red stain and, in our opinion, is the best technique for the demonstration of amyloid deposits.

Perineurioma.

Perineurioma is a rare, probably benign peripheral nerve sheath neoplasm. Perineurial cell origin is most efficiently demonstrated immunohistochemically by positivity for epithelial membrane antigen and negativity for S-100 protein and Leu 7.

Elastin fibers resembling Sporothrix schenkii in the skin of a patient with acquired immunodeficiency syndrome.

We describe a patient with the acquired immunodeficiency syndrome who presented with an erythematous skin rash on his trunk and extremities. Initial histologic examination of a skin biopsy revealed silver-staining elements resembling Sporothrix schenkii. Additional histochemical and ultrastructural studies revealed that these elements were elastin fibers rather than fungi. The literature describing pseudofungal infections is reviewed.

AgNOR counts as a discriminator of lesions of the endocervix.

Recently the argyrophil for staining proteins associated with nucleolar organizing regions (AgNORs) has been applied widely in cytohistopathology in various malignancies. Nucleolar organizer region-associated proteins (NORs) are located on the short arm of chromosomes 13, 14, 15, 21 and 22. We applied the technique to 78 cytologic smears from the endocervix stained with the Papanicolaou technique. These included 36 normal endocervical cases, 17 reactive endocervical cases, 19 dysplastic endocervical cases and 6 endocervical adenocarcinoma cases. Statistically significant differences were found between AgNOR counts from normal endocervical smears and smears of endocervical gland dysplasia (P < .001), between normal endocervical smears and smears of endocervical adenocarcinoma (P < .001), between reactive endocervical smears and smears of endocervical gland dysplasia (P < .001) and between reactive endocervical smears and endocervical adenocarcinoma (P < .005). The AgNOR technique appears useful as an adjunct in the diagnosis of endocervical lesions.

Ovarian lymphoma and serous carcinoma of low malignant potential arising in the same ovary. A case report with literature review of 14 primary ovarian lymphomas.

Ovarian lymphoma was incidentally identified in the ovary of a 31-year-old patient who underwent surgical exploration for an ovarian mass. The 6-cm mass was a serous carcinoma of low malignant potential and was located in the same ovary with the lymphoma. The lymphomatous nodule measured 1.5 cm and was diagnosed as diffuse, large-cell lymphoma of B-cell phenotype. Careful search during surgery, as well as extensive postoperative workup, showed no evidence of spread of either tumor type beyond the ovary. In a small pilot study, we examined 37 randomly selected oophorectomy specimens to determine the possible occurrence of lymphoid tissue in the ovary that could serve as substrate for development of ovarian lymphoma. Variable numbers of lymphocytes were identified in 34 of 37 ovaries, mainly in association with common ovarian lesions. This finding and the clinicopathologic data of 14 other reported cases of ovarian lymphoma provide evidence that lymphomas can arise primarily in the ovary.

Evidence for cytoprotection by prostaglandin E1 with normothermic hepatic ischemia.

Although the liver is relatively resistant to normothermic ischemia, prolonged periods of inflow occlusion have produced evidence of hepatocyte injury. We have developed an animal model of liver ischemia using the pig and maintaining subtotal inflow (hepatic artery and portal vein) occlusion, allowing mesenteric portal decompression via patent portal veins through the caudate lobe, obviating the need for portosystemic shunting. This produced biochemical [aspartate transaminase (AST), lactate dehydrogenase (LDH)] and histopathologic evidence, using a microscopic grading system, of hepatocyte necrosis after 2 hr of normothermic ischemia. By administration of prostaglandin E1 (PGE1) prior to and during inflow occlusion, we have produced a statistically significant reduction in LDH (1085.9 +/- 413.5 U/liter compared to 669.1 +/- 161.4 U/liter) and AST (236.5 +/- 80.4 U/liter compared to 85.1 +/- 39.7 U/liter) (P < 0.05) between control and PGE1 animals 24 hr after reperfusion. Moreover, using the blinded microscopic grading system for hepatocellular necrosis, we have found significantly less (2.86 +/- 0.90 compared to 1.57 +/- 1.13, P < 0.01) necrosis when control and PGE1 animals were compared. Our experimental model supports the hypothesis that PGE1 exerts a cytoprotective effect during prolonged normothermic hepatic ischemia but does not aid in elucidating a mechanism for this effect.

Artifactual endocervical atypia induced by endocervical brush collection.

The cytologic distinctions between artifactual atypia induced by endocervical brush collection, endocervical glandular repair, and endocervical glandular dysplasia or neoplasia are often difficult. This difficulty is amplified by the lack of accepted cytologic criteria for endocervical glandular dysplasia, and the fact that earlier studies defining the significant cytologic features of endocervical adenocarcinoma in situ and endocervical adenocarcinoma (endocervical neoplasia) utilized a swab for endocervical cell retrieval. With the almost universal adoption of the endocervical brush, it is important to redefine those cytologic characteristics that differentiate true endocervical glandular dysplasia or neoplasia from reactive or reparative processes and instrument artifact. From our data, it appears that the classically described cytologic discriminators between a negative smear and smears of endocervical dysplasia or neoplasia are basically unchanged with some minor modifications for endocervical brush-collected samples.

Metastatic signet ring carcinoma of the breast as a source of positive cervicovaginal cytology. A case report.

The cellular manifestations of extrauterine cancer have been well documented. While finding metastatic carcinoma in gynecologic specimens should not be unexpected, descriptions of certain types of neoplasms are not well represented in the cytology literature. We describe the clinical, cytopathologic and histologic features of a case of signet ring cell breast carcinoma metastatic to the uterine cervix. Signet ring cell breast carcinoma is a rare neoplasm, and its possible histogenesis is discussed.

Primary prostatic signet-ring cell carcinoma.

We report an uncommon case of primary prostatic signet-ring cell carcinoma which meets all criteria that define this clinicopathologic entity. Histologically, the tumor showed three different growth patterns, all of which contained large numbers of signet-ring cells. The predominant pattern, comprising approximately 50 percent of the tumor, was solid sheets of pure signet-ring cells. An intriguing finding was the presence of intestinal metaplasia involving the prostatic urethra and the large periurethral ducts. All mucin stains were intensely positive within the signet-ring cells and in the mucin lakes. Signet-ring cells stained positively for prostatic specific antigen, prostatic acid phosphatase, and carcinoembryonic antigen immunoperoxidase markers. Our patient presented with symptoms of urinary tract obstruction and locally widespread disease, infiltrating the rectum and the bladder, thus demonstrating the aggressive biologic behavior that traditionally has been ascribed to signet-ring cell carcinomas.

Papanicolaou smears in pregnancy. Positivity of exfoliated cells for human chorionic gonadotropin and human placental lactogen.

Trophoblastic cells are seen rarely in cervical exfoliative cytology during normal pregnancy but are thought to occur with increasing frequency in the clinical setting of threatened abortion. We performed a clinicopathologic and immunologic study to determine the significance of multinucleate syncytiotrophoblastic and cytotrophoblastic cells in cervicovaginal smears from 13 women identified by cytomorphologic screening during a six-year period. Control groups included 11 patients who subsequently had spontaneous abortions and 15 patients with uneventful pregnancies. Immunocytochemistry was performed using a cocktail of antihuman chorionic gonadotropin and antihuman placental lactogen antisera. Five of the 13 screen-positive cases, 1 of the 11 spontaneous abortion cases and 0 of the 15 normal pregnancies were positive on immunostaining. Clinical follow-up showed that none of the screen-positive pregnancies, including those also positive on immunostaining, ended in spontaneous abortion. Further, there was no significant difference in fetal weight or Apgar scores between the controls and the screen-positive group. The presence of trophoblastic cells on cervicovaginal smears during pregnancy is not a reliable indicator of impending abortion.

Immunohistochemical localization of amyloid beta-protein deposits in extracerebral tissues of patients with Alzheimer's disease.

An autopsy study was conducted on patients with Alzheimer's disease in order to explore the possibility of amyloid beta-protein deposits in tissues other than the brain. Immunoperoxidase staining techniques were employed using an amyloid beta-protein antiserum as primary antibody; paraffin sections of kidney, liver, heart, lung, spleen, bone marrow, colon, stomach, adrenal, thyroid, and brain were examined. Our autopsy cases were divided into two groups. The first group comprised 10 patients with Alzheimer's disease. The second group consisted of eight control cases, of age-matched individuals, that died of unrelated causes and showed no clinicopathologic evidence of Alzheimer's disease. Identification was made of strong, although focal, positive staining in two kidneys and one lung of three different patients with Alzheimer's disease. All other tissues, including the control cases, showed negative staining.

Spinal arterial aneurysm: case report.

Isolated aneurysms of the spinal artery (not associated with arteriovenous malformations) are exceptionally rare. Fewer than 17 cases have been reported in the literature. We report a case of an isolated spinal artery aneurysm causing acute subarachnoid hemorrhage. Spinal artery aneurysms are contrasted with the more common intracranial aneurysms in terms of presentation and pathogenesis. The various clinical presentations of spinal artery aneurysms are discussed as well. A summary of all reported cases of spinal aneurysms, with and without associated arteriovenous malformations, is listed.

Multinodular goiter of the thyroid mimicking malignancy: diagnostic pitfalls in fine-needle aspiration biopsy.

A case of multinodular goiter with multicentric papillary hyperplasia is presented with cytologic features suggestive of thyroid papillary carcinoma. While the cytologic criteria for papillary thyroid carcinoma is well defined, occasional diagnostic difficulties can arise. Cytologically, the presence of focal papillary aggregates, the presence of a psammoma body within a background of copious colloid and scattered follicular cells led to diagnostic confusion. Histologically, the presence of secondary follicles in the papillae and protrusion of the papillary structures into colloid lakes supported the diagnosis of goiter. It is our opinion that most, if not all, of these difficulties can be circumvented by the incorporation of all major and some minor cytologic criteria for papillary carcinoma in the analysis of such lesions. Single criteria for papillary carcinoma, either major or minor, is not sufficient.