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.

Prevalence of enteric pathogens in HIV-related diarrhea in the midwest.

HIV disease is often associated with the condition of diarrhea, which may be accompanied by enteric infection or gastrointestinal tumor. This study prospectively investigated 27 episodes of chronic diarrhea in 24 patients with HIV infection. Upper endoscopy and sigmoidoscopy with biopsies at three sites (distal duodenum, sigmoid colon, and rectum) and viral and mycobacterial blood cultures were performed. Stool specimens were sent for standard tests. A primary infectious diagnosis was found in 10 (37%) of 27 episodes: cytomegalovirus (CMV) colitis (n = 4), 3 microsporidiosis (n = 3), cryptosporidiosis (n = 2), and colonic histoplasmosis (n = 1). Patients with CD4 counts of less than 50 cells/mm3 and with lower albumin levels were more likely to have a primary infectious diagnosis. Adenovirus was found in 7 cases but was often associated with another organism; these were not considered to be primary diagnoses. Blood cultures for viruses were not useful, and all mycobacterial cultures were negative. A flexible sigmoidoscopy with histologic examination and culture of biopsy samples were the diagnostic tools that yielded most infectious diagnoses. Follow-up showed that two thirds of patients improved with nonspecific antidiarrheal medications regardless of diagnosis. The study supports a minimalistic approach to the problem of diarrhea in patients with HIV infection. Upper and lower endoscopy lead to a precise diagnosis in a minority of cases, and the outcome was similar in patients with or without a primary infectious diagnosis.

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.

Sjögren's syndrome salivary gland immunopathology: increased laminin expression precedes lymphocytic infiltration.

Previous studies have demonstrated increased expression of a laminin-like protein in labial salivary glands from Sjögren's syndrome (SS) patients. The objective of the present study was to verify the identity of this protein and to compare lymphocytic infiltration and laminin expression in minor salivary gland ductal epithelium. This was carried out by comparing laminin protein and laminin mRNA expression in 13 SS patients, 11 normal controls, and 12 patients with non-specific sialoadenitis. Laminin protein and laminin mRNA expression was determined using immunoperoxidase (IP) and in situ hybridization (ISH) techniques, respectively. In addition, the relationship between lymphocytic infiltration and laminin expression was evaluated on adjacent serial salivary gland sections from SS patients, using routine histological methods and IP immunohistochemistry. Biopsies from SS patients showed significant increases in staining for both laminin protein and laminin mRNA compared to normal controls. On seven of the eight SS samples that showed significant laminin protein staining, the ductal epithelial staining occurred in the absence of periductal lymphocytic foci. Results of the ISH assay strongly suggest that the increased expression of the laminin-like protein is laminin, since the cDNA probe was specific for the B1 chain of laminin. In addition, this increased expression in ductal epithelial cells occurs without significant lymphocytic infiltration. These studies provide further evidence that altered laminin expression is an early event associated with salivary gland pathology in SS, since these data demonstrate a potential pathologic event prior to the arrival of lymphocytes. Further studies are underway to examine the relationship between laminin and lymphocytic infiltration in salivary gland pathology.

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.

Monoclonal antibody detection of laminin in minor salivary glands of patients with Sjögren's syndrome.

The potential roles of the basement membrane proteins, laminin and fibronectin, and the cytoskeletal protein, tubulin, were assessed in the pathogenesis of Sjögren's Syndrome (SS) by comparing their expressions in SS with normal labial salivary gland (LSG) tissue. Laminin, fibronectin and tubulin expression were determined using well characterized monoclonal antibodies in the peroxidase anti-peroxidase technique on formalin-fixed LSG's from patients with SS and normal controls. Characteristic periductal staining for laminin occurred in the LSG's of 14/18 SS patients scored by one observer and 16/18 scored by the second observer. Staining of LSG's for laminin occurred in 2/35 control specimens consisting of 15 normal LSG's and 20 inflammatory lesions with attached normal LSG. The staining which occurred in the two controls was diffuse and 'non-specific' in one case, and indistinguishable from the characteristic periductal staining found in SS in the other case. Among the 20 controls containing inflammatory lesions, four showed diffuse staining for laminin within the actual lesion, but the adjacent LSG's did not stain. No statistically significant difference between SS and normal tissues stained by anti-fibronectin and anti-tubulin was observed. The study concluded that there was an increase in laminin or a laminin-like substance on salivary ductal epithelia of SS patients. This suggests a potential role for laminin in the pathologic mechanism and may indicate that increased laminin expression is a marker for SS.

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.