On the question of cognitive limits in diagnostic histopathology.

From a solely morphological point of view, histopathological diagnosis is subject to interpretation variables that may be investigated from an epistemological aspect. On the basis of the most suitable ways of approach, the authors examine some theoretical aspects involved in writing a histopathological report. In particular, the following are considered: problems regarding the perception of shapes, induction, deduction, abduction and some aspects of formal logic connected with the evaluation of immunohistochemical investigations. The main reasons for diagnostic mistakes are underlined, and the opportunity for an awareness of the logical and mental mechanisms involved in the evaluation of morphological data is outlined.

Emergency catheter probe endoscopic sonography (CP-EUS): an effective procedure in the assessment of a bleeding gangliocytic paraganglioma.

Catheter probe endoscopic sonography is a relatively rapid and safe procedure, carried out during standard endoscopy, capable of distinguishing solid from cystic lesions and vascular from avascular masses. Herein we discuss the role of catheter probe endoscopic sonography in the emergency assessment of a patient with recent and severe bleeding from an ulcerated polyp, arising from the papilla. During the endoscopy, catheter probe endoscopic sonography showed the solid and submucosal nature of the lesion, suggesting its localised and benign nature and, most importantly, demonstrating the high risk of rebleeding from vascular structures communicating with the ulcer. Because of this finding three metallic endoclips were positioned. The lesion was not removed endoscopically because of its difficult position and the high risk of haemorrhage. The mass, removed through a duodenotomy, was shown to be a gangliocytic paraganglioma, an uncommon tumour, frequently resulting in surgery because of abdominal pain and gastrointestinal bleeding.

Oral mucosal dysplastic lesions and early squamous cell carcinomas: underdiagnosis from incisional biopsy.

OBJECTIVES: To evaluate the degree and causes of underdiagnosis of incisional biopsy in oral potentially malignant lesions (PML). DESIGN: Cross-sectional retrospective study. MATERIALS AND METHODS: All pathology slides (incisional biopsy and resection specimen) from 46 patients with oral PML were reviewed and scored blind. The provisional diagnosis was considered in order to provide underdiagnosis or overdiagnosis according to whether this score was lower or higher than the final diagnosis. MAIN OUTCOME MEASURES: Concordance between the scores for provisional and final diagnoses was compared for reviewed and unreviewed assessments. RESULTS: Upon review, underdiagnosis significantly decreased from 23.9% to 4.4% (P=0.016, chi-square with the Yates' correction). As the underdiagnosis ratio was not significantly influenced by intra- or inter-observer variability, it is likely to be related to pathologists' interpretation difficulties when examining incisional biopsy specimens. CONCLUSIONS: The good quality of incisional biopsy samples was demonstrated, but clinicians should be conscious of the possible underdiagnosis by incisional biopsy when planning therapy in suspected early oral squamous cell carcinoma lesions.

Biologic differences between noninvasive papillary urothelial neoplasms of low malignant potential and low-grade (grade 1) papillary carcinomas of the bladder.

We investigated the expression of oncogenes p53, c-erbB-2, and bcl-2 and cell proliferative activity in 62 newly diagnosed superficial pTa papillary bladder tumors. Based on the 1998 World Health Organization/International Society of Urological Pathology (WHO/ISUP) and 1999 WHO classifications, 19 were urothelial neoplasias of low malignant potential (LMP) and 43 low-grade (grade 1) papillary carcinomas. All the patients underwent transurethral resection and were followed up to 97 months; 42 had recurrences. Initial biopsies were tested for p53, c-erbB-2, and bcl-2 proteins using DO7, CB11, and bcl-2 124 monoclonal antibodies. Cell proliferation was assessed by MIB-1 mAb and mitotic count. LMP had significantly lower MIB-1 (p = 0.002) and p53 immunopositivity (p = 0.03), mitotic count (p = 0.006), and recurrence rates (p = 0.04) than did grade 1 cases, whereas no difference was observed for c-erbB-2 and bcl-2 expression. The median disease-free survival for LMP was 76 months but only 15 months for grade 1 cases (p = 0.002). Although the cohort is small, the results indicate that the distinction between LMP and low-grade (grade 1) papillary urothelial neoplasias, as proposed by the 1998 WHO/ISUP and 1999 WHO classifications, reflects different biologic activity and clinical behavior; however, a long-term follow-up is advisable also for patients with LMP.

One hundred consecutive advanced breast biopsy instrumentation procedures: complications, costs, and outcome.

BACKGROUND: Needle localization and excision have been the preferred techniques for treating nonpalpable mammographic abnormalities. Recently, a less invasive approach, using the Advanced Breast Biopsy Instrumentation (ABBI) system, was introduced. This study was undertaken to determine the feasibility, utility, and cost of this new alternative approach. METHODS: Between April 1996 and May 1997, 100 consecutive women underwent excisional breast biopsies using the ABBI system. Demographic information, mammographic findings, pathological findings, hospital/professional fees, complications, and subsequent interventions were documented. RESULTS: Excisional biopsies using the ABBI system were successful for 99 women (average age, 62 years; range, 34-87 years). Of the 99 lesions removed with the ABBI system, 27 were microcalcifications, 60 were suspicious solid nodules, and 12 were nodules with microcalcifications. The ABBI system was used in an outpatient surgical setting, with only one patient requiring sedation (because of anxiety). Cancer was seen in the biopsy specimens for 18 patients, seven of whom (35%) exhibited no residual tumor at the time of definitive treatment. Postoperative hematomas occurred in two patients; one hematoma required surgical drainage. One missed cancer was detected in follow-up mammograms 6 months after biopsy. The total average procedural cost was $3406.44 +/- 486.63. CONCLUSIONS: Excisional breast biopsy using the ABBI system is an effective diagnostic method. It has a low complication rate, and its cost is comparable to that of classical needle localization.

Agglomeration inhibition reflected stone-forming activity during long-term potassium citrate therapy in calcium stone formers.

OBJECTIVES: The agglomeration of preformed crystals of calcium oxalate has been hypothesized to be the rate-limiting step in renal stone-forming activity (SFA). The effect of urine on the in vitro inhibition of agglomeration of seed crystals of calcium oxalate monohydrate, designated [tm], has been used to monitor SFA in calcium oxalate stone formers (CaOxSF). The objective of the present study was to determine whether [tm] could be used to help monitor the long-term effectiveness of oral potassium citrate therapy (K-Cit-Rx) in CaOxSF. METHODS: Clinic and radiographic (or ultrasound) reports were evaluated for 80 patients, aged 20 to 72 years, 55 men and 25 women, who were treated with oral K-Cit for recurrent calcium oxalate urolithiasis at the Ochsner Stone Clinic between January 1992 and July 1996. Seventy-five of these patients had at least one 24-hour citrate excretion rate of less than 3.0 mm/day before or after K-Cit-Rx. SFA graded on a scale of -2 to +2 by radiographic criteria was combined with information on stone passage to evaluate clinical stone status, and 24-hour urine collections were evaluated for volume, pH, calcium, citrate, uric acid, oxalate, creatinine, and [tm] on free diet before and after 6 to 53 months of K-Cit-Rx. Historical information on procedures performed for urolithiasis before and on K-Cit-Rx was also reviewed. RESULTS: K-Cit-Rx resulted in increased urine pH (P <0.0001) and decreased calcium (P=0.0475), [tm] (P=0.0045), number of stones passed per year (P=0.0016), and remedial procedures per year (P <0.0001). Patients taking allopurinol in addition to K-Cit required higher doses (P <0.0001) of K-Cit to control their disease, had lower pretreatment urine pH (P=0.0493), and showed greater increase in urine citrate (P=0.0092) than those on K-Cit alone. Those taking high-dose K-Cit were younger (P=0.0363) and showed greater decrease in SFA (P=0.0005) than those taking lower doses. A small group of 10 medication refractory patients, who retained (n=9) or increased (n=1) their stone burden during K-Cit-Rx, was identified. Compared with the medication-responsive group, the refractory patients were older (P=0.0124), and had greatly increased SFA (P <0.0001) and higher (P=0.0347) urine pH before and during (P=0.0173) treatment (data not shown). CONCLUSIONS: The data confirm that [tm] can be used not only to verify previously documented stone formation rate but also to help evaluate the long-term effectiveness of therapy. In this report, changes in [tm] after K-Cit-Rx reflected decreased stone formation rate and decreased remedial procedures.

Stereotactic excisional breast biopsies utilizing the advanced breast biopsy instrumentation system.

OBJECTIVE: To compare the stereotactic excisional breast biopsy ABBI (Advanced Breast Biopsy Instrumentation) system with "open" excisional breast biopsy with needle localization. METHODS: Twenty-three women underwent excisional breast biopsy using the ABBI system, 23 women concomitantly underwent needle localization and excisional breast biopsy. All women had mammograms displaying microcalcifications or nonpalpable noncystic nodular densities suspicious for cancer. RESULTS: Biopsies with ABBI were undertaken with local anesthesia whereas needle localization biopsies were undertaken using general anesthesia. The ABBI system allowed completion mammography. Although preoperative mammograms were comparable, biopsy specimen diameter, volume, and weight were less with ABBI, and patient acceptance was higher. Efficacy, procedural duration, and blood loss were not different between the techniques. CONCLUSIONS: The ABBI system is a minimally invasive yet efficacious excisional breast biopsy technique. It is utilized with local anesthesia in an environment more relaxed and less expensive than the operating room. It allows for smaller biopsy specimens and higher patient acceptance and is as efficacious as needle localization biopsy techniques. The ABBI system belongs in the surgical armamentarium against indeterminant nonpalpable mammographic breast lesions.

High and low risk prostate carcinoma determined by histologic grade and proliferative activity.

BACKGROUND: Histologic grade of differentiation is a strong prognostic factor for prostate carcinoma. However, most tumors fall in the intermediate group. Nuclear and nucleolar morphometry and analysis of the argyrophilic nucleolar organizer regions (AgNORs) were performed to improve prognosis, especially for patients with intermediate histologic grade tumors. METHODS: Core needle biopsies from 65 patients with primary prostate carcinoma at diagnosis were studied. Patients received only hormone therapy. Formalin fixed and paraffin embedded sections were stained with the method of Ploton. The mean AgNOR count was calculated in 100 tumor cells for each case. Nuclear and nucleolar areas from 100 cells were measured with an automated image analyzer. One-way analysis of variance and uni- and multivariate survival analyses were used for statistical evaluation. RESULTS: In the whole series, World Health Organization (WHO) tumor grade, nuclear and nucleolar areas, and AgNOR counts were correlated with survival time. By multivariate analysis, only AgNOR counts retained independent prognostic significance. In WHO Grade 2 carcinoma, the 5-year survival rate for patients with AgNOR/cell < or = 7.84 was 77%, but was only 12% for those with higher counts (P < 0.0001). These survival rates were similar to those obtained when patients with WHO Grade 1 carcinoma and Grade 2 carcinoma plus low AgNOR counts were compared with patients with Grade 3 carcinoma and Grade 2 carcinoma plus high AgNOR counts. In Gleason intermediate Grade 6 and 7 carcinomas, the 5-year survival rate for patients with AgNOR/cell < or = 7.84 was 71%, but was only 7% for those having higher counts (P = 0.0001). CONCLUSIONS: Nuclear and nucleolar areas, as well as AgNOR counts, supplement histologic grading in the prognostic assessment of prostate carcinoma in patients receiving only hormone therapy. AgNOR count also is a prognostic factor for patients with intermediate grade tumors. The combination of histologic grade and proliferative activity allows the stratification of patients into low and high risk groups.

[Signet-ring-cell adenoma of the thyroid: description of a case and review of the literature]. / Adenoma di cellule ad anello con castone della tiroide: descrizione di un caso e revisione della letteratura.

An occasional finding of a signet-ring cell type adenoma, occurring in a 81-year-old man, suffering from inoperable pharyngo-laryngeal carcinoma, is described. Multinodular thyroid parenchyma was excided in performing tracheostomy and histologically examined. On the basis of extensive morphological, histochemical and immunohistochemical observations and of reviewed literature, an unifying morphogenetic interpretation of the signet-ring cell transformation is proposed, with special reference to the pathogenesis of this cytotype and the significance of the cytostructural and cytometabolic characteristics. Problems related to the differential diagnosis and clinicopathological correlation are also discussed.

Monosomy 6q: report on four new cases.

We report on four patients with partial monosomy of the long arm of chromosome 6: two children presenting with an interstitial deletion del(6)(q14q16), the two others presenting with a terminal deletion del(6)(q25qter). These patients are compared with previous reports in the literature: 16 cases of terminal deletion and 17 cases of interstitial deletion. The deletions most often occur de novo. Mental retardation is always described. Dysmorphic facial features range between minor and major. There may be associated visceral abnormalities. After comparing the size and the localisation of the deletions with clinical data, we are now able to suggest a clinical localisation on chromosome 6.

[Value of ultrasonic diagnosis of fetal malformations in the detection of chromosomal abnormalities]. / Intérêt du diagnostic échographique des malformations foetales dans le dépistage des anomalies chromosomiques.

We report 118 foetal karyotypes studied on the basis of ultrasonographic warning signs which appeared in pregnancies with no significant risk of chromosomal abnormalities, judging from the personal and familial histories. Foetal karyotyping was performed either in amniotic fluid (AF) or in foetal blood. The ultrasonographic warning signs fell into 3 categories: (1) intrauterine growth retardation (IUGR) which was harmonious and below the 5th percentile, without foetal malformation at ultrasonography and without maternal cause (doppler examination, normal Pourcelot's index): 30 cases (24.4%). IUGR was isolated in 22 cases and associated in 8 cases with abnormal amounts of amniotic fluid: oligoamnios 6, hydramnios 2; (2) Isolated abnormality of AF volume: 22 cases (18.8%); hydramnios 19 and oligoamnios 3; (3) Foetal malformations in 66 cases (56%), including 16 central nervous system malformations, 4 cystic hygromas, 10 urinary tract malformations, 9 foetal effusions, 9 abdominal wall abnormalities, 7 gastrointestinal malformations, 5 malformations of the limb and 3 cardiac malformations. The mothers' mean age was 27.5 +/- 4.5 years; the mean term of pregnancy at the time of foetal karyotyping was 28 +/- 6.5 AW. In 51% of the cases the ultrasonographic warning sign was discovered after 29 AW. Among the 118 foetal karyotypes studied, 12 chromosomal abnormalities (10.6%) were detected. During the same period, 712 foetal karyotypes were studied in women aged 38 or more and 18 chromosomal abnormalities (2.53%) were detected. This study confirms that more chromosomal abnormalities can be detected by ultrasonographic warning signs than by relying on the mother's age which is the most frequent reason for foetal karyotype studies. Ultrasonography performed during the second trimester of pregnancy is of value to evaluate foetal growth and the amount of AF and to investigate for possible foetal malformations.

Signet-ring cell carcinoid of the gallbladder.

A case of signet-ring cell carcinoid of the gallbladder is reported. The tumour diffusely infiltrated the gallbladder wall and extensively ulcerated the mucosa. Neoplastic nests were composed of numerous signet-ring cells mixed with clear endocrine cells. The latter expressed chromogranin A, gastrin and somatostatin and contained neurosecretory granules. The diagnostic problem of differentiating between signet-ring cell carcinomas and composite adenocarcinoma-carcinoid tumours is discussed.

[Role of direct immunofluorescence in the diagnosis of oral lichen planus]. / Ruolo della immunofluorescenza diretta nella diagnosi del lichen planus orale.

A series of 25 cases with clinical signs indicative of oral lichen planus was examined. Samples stained with haematoxylin-eosin as for traditional histology and others for DIF were taken in each case. The results obtained by both techniques were then compared with the clinical picture. It is concluded that DIF is a valuable diagnostic aid in doubtful cases.

[Keratotic lesions of the oral cavity. Notes on histopathologic differential diagnosis in leukoplakia, lichen planus, lupus erythematosus. Cases investigation]. / Lesioni cheratosiche del cavo orale. Note di diagnosi differenziale istopatologica tra leucoplachia, lichen planus, lupus eritematoso. Indagine casistica.

A series of 24 white mouth lesions variously diagnosed as leukoplakia, lichen planus and discord lupus erythematosus is examined. A number of histological parameters were investigated using samples stained with haematoxylin-eosin and orcein and by Wohlgemulh's test. The 24 cases were also assessed by direct immunofluorescence (DIF) using the standard techniques. The aim of the study was to discover which of the histological and DIF findings were most helpful for diagnosis. The results confirm the view that histological diagnosis is only possible in some cases and that DIF helps to clarify histologically uncertain ones. Even so, clinical examination of the patient remains essential in order to eliminate the uncertainty created by the histological findings. It therefore follows that close collaboration between clinician and pathologist is essential.

[Morphologic characteristics of leukoplakias of the oral cavity and review of case material]. / Considerazioni sulle caratteristiche morfologiche delle leucoplachie del cavo orale e revisione casistica.

Cases of oral mucosa leukoplakias are presented. The authors discuss histologic features, clinical and prognostic findings.