Traumatic shock and electroshock: the difficult relationship between anatomic pathology and psychiatry in the early 20th century.

In the conviction that a look at the past can contribute to a better understanding of the present in the field of science too, we discuss here two aspects of the relationship between early 20th century anatomic pathology and psychiatry that have received very little attention, in Italy at least. There was much debate between these two disciplines throughout the 19th century, which began to lose momentum in the early years of the 20th, with the arrival on the scene of schizophrenia (a disease histologically sine materia) in all its epidemiological relevance.The First World War also contributed to the separation between psychiatry and pathology, which unfolded in the fruitless attempts to identify a histopathological justification for the psychological trauma known as shell shock. This condition was defined at the time as a "strange disorder" with very spectacular symptoms (memory loss, trembling, hallucinations, blindness with no apparent organic cause, dysesthesias, myoclonus, bizarre postures, hemiplegia, and more), that may have found neuropathological grounds only some hundred years later.Among the doctors with a passed involvement in the conflict, Ugo Cerletti, the inventor of electroshock treatment, focused on the problem of schizophrenia without abandoning his efforts to identify its organic factors: if inducing a controlled electric shock, just like an experimentally-induced epileptic seizure, seems to allay the psychotic symptoms and heal the patient, then what happens inside the brain? In seeking histological proof of the clinical effects of electroconvulsive therapy ("the destruction of the pathological synapses"), and attempting to isolate molecules (that he called acroagonins) he believed to be synthesized by neurons exposed to strong electric stimulation, Cerletti extended a hand towards anatomic pathology, and took the first steps towards a neurochemical perspective. However his dedication to finding a microscopic explanation for schizophrenia - in the name of a "somatist" approach that, some years earlier, the psychiatrist Enrico Morselli had labelled "histomania" - was unable to prevent psychiatry from moving further and further away from anatomic pathology.

Malignant peripheral nerve sheath tumor of the bladder A case report.

Malignant peripheral nerve sheath tumor (MPNST) is an uncommon malignant tumor often associated with Neurofibromatosis type 1 (NF1). Although different soft tissue mesenchymal tumors may arise in the bladder, MPNST is a very rare occurrence. Here, we present a case of MPNST of the bladder in a 50 year old patient with NF1 with involvement of the entire wall of the organ leading to a functional exclusion. The principal differential diagnoses and a short review of the literature are presented.

Enrico Sertoli and the supporting cells of the testis "Morphology is function".

In 1865, Enrico Sertoli, at the age of 23, published an article in his own name entitled: "About the existence of special branched cells in the seminiferous tubules of the human testis". These were Sertoli's ideal cells; in this paper he arrived at a perspicacious description of the morphology and function of these cells and in the subsequent articles he investigated the topic of spermatogenesis. Despite the importance of Sertoli's discovery, the attention of the scientific literature remained very limited after Sertoli's death for half a century and the partial eclipse finished only in the 1970s of the twentieth century.

Pathologica in the time of "Spanish flu".

The pandemic "Spanish flu", that in a few weeks of the autumn 1918 caused in Italy a number of deaths between 350.000 and 600.000, was widely discussed by the scientific community, although very little of that debate leaked out, because of the military censorship.In the present article we comment on the original papers describing the hemorrhagic pneumonia, and on discussions about the ideas of the origin of the pandemic infection (Pfeiffer bacillus, vs streptococcus or other bacteria vs a "viral hypotesis") that occurred in Pathologica during and soon after that ominous pandemia.

Cystic mature teratoma and epidermoid cyst associated with granulosa cell tumour: a rare ovarian scenario. Two case reports and review of the literature.

We describe two cases of association between an ovarian granulosa cell tumour and a cystic mature teratoma and an epidermoid cyst. These are very rare combinations that might lead to incorrect diagnostic interpretation, since the simultaneous presence, on routine gross and microscopic examination, of a cystic squamous lesion, intimately connected with (case 1), or contralateral to (case 2) a solid, histologically trabecular or microfollicular tumour, might suggest a diagnosis of a carcinoid tumour in a mature cystic teratoma. The differential diagnostic problems and a review of the literature are presented.

The expression pattern of MUC1 (EMA) is related to tumour characteristics and clinical outcome of invasive ductal breast carcinoma.

AIMS: To clarify MUC1 patterns in invasive ductal breast carcinoma and to relate them to clinicopathological parameters, coexpression of other biological markers and prognosis. METHODS AND RESULTS: Samples from 243 consecutive patients with primary ductal carcinoma were incorporated into tissue microarrays (TMAs). Slides were stained for MUC1, oestrogen receptor (ER), progesterone receptor (PR), Her2/neu, p53 and cyclin D1. Apical membrane MUC1 expression was associated with smaller tumours (P = 0.001), lower tumour grades (P < 0.001), PR positivity (P = 0.003) and increased overall survival (OS; P = 0.030). Diffuse cytoplasmic MUC1 expression was associated with cyclin D1 positivity (P = 0.009) and increased relapse-free survival (RFS; P = 0.034). Negativity for MUC1 was associated with ER negativity (P = 0.004), PR negativity (P = 0.001) and cyclin D1 negativity (P = 0.009). In stepwise multivariate analysis MUC1 negativity was an independent predictor of both RFS [hazard ratio (HR) 3.5, 95% confidence interval (CI) 1.5, 8.5; P = 0.005] and OS (HR 14.7, 95% CI 4.9, 44.1; P < 0.001). CONCLUSIONS: The expression pattern of MUC1 in invasive ductal breast carcinoma is related to tumour characteristics and clinical outcome. In addition, negative MUC1 expression is an independent risk factor for poor RFS and OS, besides 'classical' prognostic indicators.

The expression pattern of MUC1 (EMA) is related to tumour characteristics and clinical outcome in 'pure' ductal carcinoma in situ of the breast.

AIMS: To classify MUC1 according to five predefined expression patterns in ductal carcinoma in situ (DCIS) and related clinicopathological parameters, coexpression of other biological markers and prognosis. METHODS AND RESULTS: With a manual tissue arrayer, 92% (n = 80) of the 87 DCIS samples were successfully targeted. Immunohistochemistry was carried out for MUC1, oestrogen receptor (ER), progesterone receptor (PR), Her2/Neu, p53 and cyclin D1. Entire membrane expression was related to Her2/neu negativity (P =0.042). Apical membrane expression was associated with low grade (P = 0.027), Her2/neu negativity (P = 0.014) and PR positivity (P = 0.005). Focal cytoplasmic expression was related to high grade (P = 0.006). Diffuse cytoplasmic expression was associated with high grade (P = 0.004), large tumour size (P = 0.046), Her2/neu positivity (P =0.042) and cyclin D1 positivity (P = 0.002). On the basis of these analyses the four patterns were reclassified as membranous or cytoplasmic expression. On multivariate analysis, cytoplasmic MUC1 expression (hazard ratio 8.5, 95% confidence interval 1.0, 73.0; P = 0.04) was the only independent predictor of local recurrence. CONCLUSIONS: Four patterns of MUC1 expression are recognized in DCIS that suggest a relationship to functional differentiation and can be simplified into two types that are clinically relevant and could therefore be helpful in the distinction between different subgroups of DCIS.

Re-occurrence of the CD20 molecule expression subsequent to CD20-negative relapse in diffuse large B-cell lymphoma.

We report the first case of diffuse large B-cell lymphoma (DLBCL) of the stomach displaying CD20-negative relapse after rituximab-containing treatment and the re-appearance of CD20 expression at the second failure. The loss of CD20 expression in B-cell lymphomas relapsing after rituximab is a well-known phenomenon, but its actual impact in DLBCL is difficult to estimate. This paradigmatic case suggests that CD20-expression reappearance after purging of CD20-positive clones with rituximab might be an underestimated occurrence in B-cell lymphomas. Accordingly, every relapse, whenever possible, should be histologically assessed with diagnostic and immunophenotyping purposes.

Histopathological findings after radiofrequency (RITA) treatment for prostate cancer.

Radiofrequency interstitial tumor ablation (RITA) is a thermal ablation method that uses needles and low radiofrequency (RF) energy. The aim of our study was to evaluate the histopathology of thermal lesions induced by RF energy delivered interstitially in prostate cancer patients who subsequently underwent prostatectomy, and to determine the feasibility, effectiveness and safety of this new method in a pilot study.

Elevated E-cadherin and alpha/beta-catenin expression after androgen deprivation therapy in prostate adenocarcinoma.

The histological patterns of anti-androgen-treated prostate adenocarcinoma mimic high grade tumors classified according to the widely used Gleason scoring system. However, the biological characteristics of anti-androgen treated carcinoma are largely unknown. E-cadherin, alpha-catenin, and beta-catenin adhesion molecules are down-regulated in pharmacologically untreated high grade prostate carcinoma. In this study, we used immunohistochemical techniques to investigate their expression in twenty acinar adenocarcinomas after anti-androgen therapy in prostatectomy specimens. After adrogen ablation therapy, expression of all these adhesion molecules was higher than that of pretreatment biopsies of the same patient group and high grade matched untreated controls. These results emphasize the inaccuracy of the Gleason score for anti-androgen-treated prostate adenocarcinoma and the more differentiated phenotype of prostate adenocarcinoma after anti-hormonal therapy.

Diagnostic role and prognostic significance of a simplified immunophenotypic classification of mature B cell chronic lymphoid leukemias.

We verified the diagnostic and prognostic role of a simplified immunophenotypic classification (IC) in a series of 258 patients (M/F: 1.4; median age: 64 years; median follow-up: 64 months; 75 deaths) with mature B cell lymphoid leukemias (MBC-LL) for whom no histopathological diagnosis was available because of minimal or no lymph node involvement. The IC was based on the reactivity of three pivotal immunophenotypic markers: CD5, CD23 and SIg intensity. On the basis of different expression patterns, we identified four diagnostic clusters (C) characterized by distinct clinico-biological features and different prognoses: C1 (149 patients) identified most classical B cell chronic lymphocytic leukemias (CLL-type cluster; SIg(dim)/CD5+/CD23+); C2, 38 patients whose clinico-hematological characteristics were intermediate between C1 and C3 (CLL-variant cluster; SIg(bright)/CD5+/CD23+/-or SIg(dim)/CD5-/-/CD23 indifferent); C3 (16 patients) most situations consistent with mantle cell lymphoma in leukemic phase (MCL-type cluster; SIg(bright)/CD5+/CD23-); and C4, 55 cases, most of whom were consistent with leukemic phase lymphoplasmacytic/splenic marginal zone lymphomas (LP/S-type cluster; SIg(bright)/CD5-/+/CD23 indifferent). At univariate survival analysis, prognosis worsened from C1 to C4, C2 and C3 (P = 0.0001), and this was maintained at multivariate analysis (P = 0.006), together with CD11c expression (P = 0.0043), age at diagnosis (cut-off 70 years; P = 0.0008) and platelet count (cut-off 140 x 10(9)/l; P = 0.0034). Besides recognising the two well-known situations of classic B-CLL and MCL, our IC identified situations with distinct prognostic and/or clinical behaviors.

Molecular disorders in transitional vs. peripheral zone prostate adenocarcinoma.

Loss of heterozygosity (LOH) and microsatellite instability (MSI) have been shown to be mechanisms for tumor-suppressor gene inactivation in human oncogenesis. In our study, we examined LOH and MSI using 16 polymorphic markers of DNA for chromosomes 1, 3, 7, 8, 10 and 11. Microdissected tumor samples were isolated from 32 patients, representing 11 foci of incidentally discovered prostate cancer of the transitional zone (TZ), 12 prostate cancer of the peripheral zone (PZ) and 10 of high-grade PIN. We found loss of heterozygosity in the TZ group in 91% of informative cases (10/11) with al least 1 marker compared to 58% of cases (7/12) in PZ group and 70% of cases (7/10) in the HGPIN group. Chromosome 7 showed the highest rate of allelic loss in all 3 categories, with loss of 43% of loci in PIN, 37% in TZ tumors and 31% in PZ tumors. At chromosome 11, LOH was detected in 26% of loci in the TZ group, in 7% of loci in the PZ group and in 13% of loci in the PIN group. On chromosome 8, the PZ and HGPIN group showed allelic loss in 22% and 21% of loci, respectively, compared to 10% detected in the TZ group. The TZ group showed a significant higher rate of allelic instability compared to that observed in tumor samples from the peripheral zone: 73% of cases (8/11) showed genetic alterations (RER+ phenotype) in at least 4 loci analyzed compared to 8% and 10% in the PZ and HGPIN groups, respectively (p = 0.0006). These data suggest that transitional zone carcinoma and peripheral zone carcinoma display distinct and specific genetic alterations in different chromosomes. This diversity may help explain biologic and clinical differences between carcinomas arising in these distinct zones of the prostate. Also our results strongly suggest that the RER+ mutator phenotype could be linked to early development of transitional zone prostate carcinoma.

Intravascular lymphomatosis (IL) in a child mimicking a posterior fossa tumor.

Intravascular lymphomatosis (IL) is a rare entity only recently included in lymphoma classification, whose main feature is the exclusive or predominant growth of neoplastic cells within blood vessels. The vast majority of the patients affected by IL belong to the 7th or 8th decade of life and present with skin rash or CNS diffuse necrotic or demyelinating lesions. Case report. SS, a 13-year-old girl, was admitted to a Neurosurgery Unit because of endocranic hypertension, where, after CT and MRI documenting a IV ventricle 3 cm diameter tumor, she was submitted to complete tumor excision: extemporary diagnosis was suggestive of medulloblastoma. When referred to us she had persistent fever with normal blood and spinal fluid cultures. Whole CNS MRI did not give evidence of residual or metastatic disease while CSF cytology showed only pleiocytosis. Treatment was started according to our ongoing protocol for medulloblastoma with pre-radiation chemotherapy. Before delivering radiotherapy (RT), upon review of histologic specimens, the definitive diagnosis of IL B-phenotype was made. The girl was re-admitted and, after a complete re-staging, chemotherapy was intensified according to our schedule for high-grade B-cell lymphoma and CNS was irradiated up to a total dose of 25 Gy. She remained alive in continuous complete remission at 21 months after diagnosis. The case here reported is unique for age, tumor presentation, and, so far, favourable outcome, in spite of the delayed histological diagnosis.

Macrocryosectioning of the prostate: a simple technique.

Whole mount sections of the prostate are widely used in many laboratories. Macrocryosections of the gland; that is, whole mount frozen sections of the prostate from radical prostatectomies represent a useful new research protocol. The technique is very simple and does not require expensive equipment.

Lack of CD 29 (beta1 integrin) and CD 54 (ICAM-1) adhesion molecules in intravascular lymphomatosis.

Intravascular Lymphomatosis (IL) is a rare and usually aggressive form of non-Hodgkin's lymphoma characterized by the growth of neoplastic cells within vascular lumina that usually presents with skin or central nervous system (CNS) involvement. The mechanism(s) for the selective intravascular growth of this neoplasm remain(s) unexplained. We now report clinical and immunohistologic data on surgical material from 6 cases of IL; in 4 of 6 cases, autopsies were performed. Our IL cases shared the following features: (1) B-cell lineage; (2) lack of skin involvement at presentation; (3) aggressive behavior; and (4) lack of extravascular lymphomatous masses; in addition, 1 case had an associated gastric low-grade MALT lymphoma. We studied by immunohistochemistry formalin-fixed, paraffin-embedded sections with monoclonal antibodies to molecules known to be involved in lymphocyte and endothelial adhesion phenomena, that is, CD29 (beta1 integrin subunit), CD43 (leukosialin), CD44 (H-CAM), CD54 (ICAM-1), embryonal N-CAM (e-NCAM), and EMA (episialin). In all cases, the surfaces of IL aggregates reacted for CD44 but were consistently negative for CD29; also absent was CD54. Conversely, the integrity of the endothelial cells was underscored by their even reactivity for CD29, CD44, and CD54. Given that CD29 is currently regarded as critical for lymphocyte trafficking in general and for transvascular migration in particular, and CD54 is also involved in transvascular lymphocyte migration, we conclude that their consistent absence in IL may contribute to its intravascular and disseminated distribution pattern. The rather frequent association of IL with various conventional lymphomas is known; yet, one of our cases appears to be the first report of IL associated with a low-grade MALT lymphoma.

Integrin laminin receptor profile of pulmonary squamous cell and adenocarcinomas.

The differential expression of laminin receptors has been shown to modulate the invasive capability of malignant cells. We have investigated the reactivity of human pulmonary squamous carcinomas (SSC, n = 20) and adenocarcinomas (ADC, n = 20) with monoclonal antibodies to the cytoplasmic and extracellular domains of the integrin subunits alpha3 and alpha6. Integrins containing these subunits are laminin receptors. Monoclonal antibodies to beta1 and beta4 subunits, the beta1C splice variant of beta1, as well as to Ki-67, were also used. Reverse transcription polymerase chain reaction (PCR) single-strand conformational polymorphism analysis was done to detect possible mutations in the cytodomains. All carcinomas expressed alpha3 extensively; alpha3 expression predominated (40 of 40) over alpha6 (25 of 40). In all alpha6-positive carcinomas, alpha6A was expressed, whereas alpha6B was weakly expressed only in some of them. No mutations of the intracytoplasmic domain A of alpha3 and of the A or B intracytoplasmic domains of alpha6 were shown. Notably, in normal bronchial epithelium, alpha6 colocalized with beta4, whereas in the tumors, alpha6A frequently overlapped with beta1 in a circumferential pattern; alpha6beta1 coexpression was also shown by coprecipitation experiments. Strong and extensive beta4 reactions were invariably polarized at the cell/stroma interface in SCC and ADC. An inverse correlation was found between the expression of beta1C and Ki-67. The prevalence of alpha6A in pulmonary SCC and ADC is in contrast with previous results in colonic ADC in which alpha6B prevails, and alpha6 predominates over alpha3. The absence of mutations of the cytodomains suggests that the integrin subunits of these carcinomas are potentially active. Predominance of alpha3 over alpha6 and of alpha6A over alpha6B may contribute to explain the aggressive and metastatic behavior of lung carcinomas.