William A. Stinson

Creating digital images of pathology specimens by using a flatbed scanner.

Sir: It surprised me to read of marked siderosis ascribed to Wilsons disease in a decoppered liver. Some years ago, before HFE mutations were found to underlie many cases of genetic haemochromatosis, Jacqueline Schoenlebe and I reviewed 22 hepatectomy specimens from adolescent patients seen at the Childrens Hospital of Pittsburgh who carried the diagnosis of Wilsons disease. Hepatocellular siderosis was present in ®ve of them and in two was extraordinarily marked (unpublished observations). Of course, homozygosity or heterozygosity for HFE mutations could not be excluded then, but I have wondered since if coexistent genetic abnormalities in metabolizing two metals might exacerbate one another. Perhaps it would be of interest to readers today to learn what HFE studies disclosed in the patient reported by Pilloni et al.; I think that to attribute siderosis to Wilsons disease alone would be more defensible if HFE disease had been excluded.

A simple technique for calculation of the volume of prostatic adenocarcinomas in radical prostatectomy specimens.

Tumor volume has been suggested as an important prognostic factor of prostatic adenocarcinoma (PAC) treated with radical prostatectomy (RP). The calculation of tumor volume is complicated by the difficulty in appreciation of tumor nodules at gross examination, multifocality, and variation in the shape of tumor nodules. We propose a simple technique for the calculation of tumor volume. One hundred consecutive specimens of RP were studied with special attention to the shape of tumor nodules. Most small PAC, transitional zone (TZ) PAC, peripheral zone (PZ) PAC without associated benign prostatic hyperplasia (BPH), and PZPAC with Gleasons score (GS) > 3 + 4 had an ovoid shape. Most large sized nodules of PZPAC with GS < 4 + 3 tended to mold according to the boundaries of the TZ that were themselves often compressed by hyperplastic nodules. Therefore, these large tumor nodules were crescentically shaped and had tapering pole(s). We deduced from that tendency that the ratio of height of the tumor nodule = D1 x the height/greatest horizontal diameter of the prostate (D1 = the greatest diameters of the largest section of tumor nodule). Using the mathematical formula for volume of an ellipsoid structure, we propose the following formula to calculate the volume of each tumor nodule = 0.8 x K x D1(2)x D2 (D2 = greatest diameter orthogonal to D1, and K = coefficient for correction of tumor volume due to the compression of hyperplastic nodules). K is empirically estimated as 2/3 for PZPAC in mid prostate and 1/2 for tumor nodules at the apex and base. The total tumor volume is the sum of all tumor nodule volumes. By measuring the two greatest orthogonal diameters, D, and D2, of the largest horizontal section of a tumor nodule, we were able to calculate the corresponding volume and consequently the total tumor volume of the prostate. Analysis of the calculated total tumor volume showed a good correlation with the current technique of measurement on each section of the prostate, particularly for tumors ranging from 1.5 to 3.0 cm3.

Implantable Cardioverter-Defibrillators and the Pathologist: Comment and Cautionary Notes

This paper briefly reviews the components of, the clinical uses of, the techniques to place, and the complications related to implantable cardioverter-defibrillators (ICDs). Information useful in the specific identification of ICDs is presented. A series of recommendations for the autopsy examination or postmortem explantation of ICDs by the pathologist is given. Because of the serious risk of injury to the pathologist possible with postmortem discharges of ICDs which have not been deactivated, and because of the risk of device explosion if the ICD is incinerated, a number of cautionary notes are provided. A brief case with occurrence of accidental postmortem discharge of an active ICD is also presented.

Benign Hürthle Cell Adenoma with Papillary Architecture: A Benign Lesion Mimicking Oncocytic Papillary Carcinoma

We studied the significance of encapsulated Hürthle cell thyroid nodules with papillary structures lacking the nuclear features of papillary thyroid carcinoma (PTC); 19 cases fulfilling these criteria were encountered The patients ages ranged from 22 to 40 years (32±6), and the F:M ratio was 3:1 The tumors measured from 0.5-5 cm (2±1 .1). The diameter of the tumor cell nuclei ranged from 5.6 to 7.2 microns. Many nodules had nuclei displaying a fine chromatin pattern somewhat resembling those of PTC, but these were present in <20% of the tumor cells. Immunohistochemically, there was reactivity for MIB-I in the papillary structures, negativity to focally weak reactivity for HBME and galectin-3, and negativity to moderate diffuse reactivity for CK19. Clinical follow-up from 1 to 19 years revealed no evidence of metastases in any of the cases. It is unlikely that the papillary structures in the study cases represent degenerative changes in view of the proliferative activity we have demonstrated in them. In view of (1) the encapsulation and the uniformity of the constituent cells, (2) the negative or weak immunoreactivity for galectin-3 and HBME and negative to moderate immunoreactivity for CK19, and (3) the absence or paucity of nuclear criteria for the diagnosis of PTC and the absence of lymph node metastasis in all study cases, we believe that these lesions represent the papillary variant of oncocytic follicular adenoma (Hürthle cell adenoma). Recognition of this entity is important to avoid an overdiagnosis of oncocytic PTC.

Histopathological and immunohistochemical study of papillary urothelial neoplasms of low malignant potential and grade associated with extensive invasive low-grade urothelial carcinoma

To report five cases of papillary urothelial neoplasm of low malignant potential (UNLMP) and papillary urothelial carcinoma of low grade (UCLG) associated with extensive muscle invasion, and to investigate the clinical and histopathological presentation and their immunohistochemical properties.

Identification of Isolated and Early Prostatic Adenocarcinoma in Radical Prostatectomy Specimens with Correlation to Biopsy Cores: Clinical and Pathogenetic Significance

Prostatic adenocarcinoma (PAC) is a multifocal disease. In this study, we identified isolated and small foci of PAC (ISPAC) in radical prostatectomy specimens, described the histopathologic features, investigated their zonal distribution in the prostate and their relationship with large tumor nodules, and correlated the findings with those of preceding biopsy cores. One hundred and thirty radical prostatectomy specimens performed for PAC or for urothelial carcinoma of the urinary bladder with incidental PAC were reviewed for identification of ISPAC. Prostates were serially sectioned in the horizontal plane and submitted in toto for microscopic examination. ISPAC were defined as foci of PAC measuring less than 3 mm in maximum diameter. There were 461 ISPAC identified in 114 cases. They were distributed in the transitional zone (TZ) (18 foci), the apex (73 foci), the anterior horn of the non-TZ (NTZ) (118 foci), the base (8 foci), and the remaining NTZ (244 foci). ISPAC usually consisted of groups of small acini with a GS ranging from 2 to 7 (3 + 4). GSs of ISPAC consisted of single grade or two consecutive grades equal to or lower than those of the main PAC. ISPAC were more often located in close proximity to large tumor nodules. The number of ISPAC increased with the tumor volume up to 3 cm3, then decreased as the PAC became more extensive (p value = 0.02, statistically significant). Prostates with NTZ PAC <1.5 cm3 and TZ PAC or prostates containing 4 or more than 4 ISPAC tended to be frequently associated with small foci of PAC in biopsy cores In this study, we identified ISPAC that likely represent foci of PAC in early development and account for the multicentricity and heterogeneity of PAC. ISPAC in the NTZ were common and may account for small foci of PAC or atypia in biopsy cores. Although these small foci of PAC or atypia in biopsy cores without accompanying higher GS PAC were often associated with significant PAC, they may also occasionally represent insignificant or vanishing PAC in subsequent radical prostatectomies.

High grade prostatic intraepithelial neoplasia involving small ducts and acini

with fragments of incompletely digested microorganisms forming an organic matrix on which the deposition of iron and calcium can occur (Liesengang phenomenon). Whether this defect is the expression of a common (genetic) disorder or the result of an altered immune system remains to be clarified. Apart from the urinary bladder and distal ureter, which represent 75% of all cases, malacoplakia is frequently seen in the gastrointestinal tract (15%) and kidney (12%). The involvement of other organs such as the gallbladder represents a pathological curiosity. To the best of our knowledge the first example of malacoplakia of the gallbladder was reported by Hanada et al. in 1981. They reviewed the clinicopathological features of 17 cases of cholecystic granulomas detecting four main histological types: xanthogranulomatous, foreign body, pigmented and malacoplakia. The latter (represented only by case 17 in their series) was characterized by the presence of Michaelis-Gutmann bodies in an otherwise typical xanthogranulomatous cholecystitis. Since then, two additional cases of malacoplakia involving the gallbladder have been reported in English literature. That described by Charpentier et al. arose in the setting of non-specific chronic granulomatous inflammation, while that reported by Hide et al. lacks a detailed histological description. Our case represents the first example of malacoplakia of the gallbladder associated with the presence of microorganisms, since cultures of gallbladder bile or staining for microorganisms have been negative in two of the previous reported cases and not assessed in the latter. It is possible that in those rare conditions in which bile is no longer sterile, microorganisms may represent the trigger for the Liesengang phenomenon. On the other hand, as suggested by Hanada et al. and supported by data presented by Charpentier and by the findings in the present case, malacoplakia may develop in an otherwise typical xanthogranulomatous cholecystitis. The latter is thought to arise secondary to unsuccessful phagocytosis of bile material; thus it can be speculated that xanthogranulomatous cholecystitis and malacoplakia of the gallbladder are part of the spectrum of the same disease: a disorder of phagocytosis which can present different histological features. Despite earlier descriptions that considered malacoplakia to be a benign, self-healing, process, it is now clear that rare cases are associated with significant morbidity and mortality. In these cases aggressive surgery is the treatment of choice. In the remaining cases conservative therapy is preferred. L Di Tommaso C Arizzi M Roncalli

Mitral Annular Calcification With Staphylococcus aureus Periannular Abscess

A woman presented to the hospital with generalized back pain. The patient’s medical history included systemic arterial hypertension and mild chronic renal failure. There was no history of fever or delirium. The patient was afebrile and normotensive with no respiratory distress, and findings on cardiopulmonary examination were unremarkable. Palpation of the abdomen revealed right upper quadrant tenderness without guarding. A complete blood cell count revealed leukocytosis with neutrophilia and a left shift. The patient had evidence of chronic renal failure with a mildly elevated urea. Her serum lactate level was mildly elevated, and she was admitted with a diagnosis of possible bowel ischemia. She was observed for signs of a surgical abdomen and did not receive prophylactic antibiotic therapy. Blood cultures were not performed. Three days after admission, the patient was found unresponsive, and she died shortly thereafter. A complete postmortem examination revealed no bowel ischemia. The heart weighed 400 g, secondary to mild, concentric left ventricular hypertrophy. Changes of mild congestive heart failure were present. Cultures of a 200mL purulent pericardial effusion grew abundant Staphylococcus aureus. Examination of the cardiac valves revealed severe mitral annular calcification (MAC), indicated by small dark arrows, at the junction of the left ventricle (V) and left atrium (A). The overlying thrombus had eroded and perforated the posterior mitral valve leaflet (white arrows). Microscopy of the MAC revealed amorphous basophilic calcific debris intimately associated with clusters of grampositive cocci, consistent with Staphylococcus infection. Myocardial and adrenal septic emboli were discovered, along with myocardial, renal, cerebral, and cerebellar microabscesses. Early purulent leptomeningitis was also present. Our patient’s cause of death was sepsis, secondary to a S aureus periannular abscess superimposed on MAC. With an aging population, MAC is not an uncommon finding at antemortem imaging or at postmortem exami-

The 3-dimensional structure of isolated and small foci of prostatic adenocarcinoma: the morphologic relationship between prostatic adenocarcinoma and prostatic intraepithelial neoplasia.

BackgroundTransitional histopathologic changes from high-grade prostatic intraepithelial neoplasia (HGPIN) into early prostatic adenocarcinoma (PAC) have not been well studied to date. To investigate the histogenesis of PAC, we examined isolated and small foci of PAC (ISPAC) found in prostatectomy specimens and the 3-dimensional structure of these foci. DesignTwelve consecutive radical prostatectomy specimens having ISPAC, performed for peripheral zone PAC (10 cases) and for transitional zone PAC (2 cases), of Gleason score were studied. One to 2 tissue blocks with representative sections were used. ResultsEight ISPAC, with Gleason score 3+3 had complete serial sections of the entire lesion. PAC consisted of continuous, tortuous and branching tubules and acini arising from benign ducts displaying: (a) HGPIN in 5 ISPAC and (b) no HGPIN in 3 ISAPC. At the junctions between benign epithelia with or without HGPIN and malignant epithelia, there were transitional lesions with HGPIN involving small ducts and acini. ConclusionsPAC develops as a result of multiple outpouchings of the epithelium with formation of small ducts and acini showing cytologic atypia and gradual or abrupt loss of basal cells. Grade 3 ISPAC consists of a system of continuous duct pushing into the stroma. There is also evidence suggestive of HGPIN as being both a precursor lesion and an accompanying lesion of PAC.