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Cowden Syndrome (CS) is an autosomal dominant disorder characterized by hamartomatous growth in several organs and by an increased risk of malignancies, which makes its recognition essential to undertake risk reduction measures. Although the involvement of gastrointestinal tract is extremely common, awareness of this entity among gastroenterologists appears limited. We report on two unrelated patients: a 46-year-old male and a 38-year-old woman, who were referred to the Genetic Clinic because of the endoscopic finding of multiple colorectal polyps. Despite both displayed striking clinical (and, in the first case, familial) manifestations of Cowden Syndrome (PTEN Hamartoma Tumor Syndrome-PHTS), they had not been recognized before. Diagnosis of PHTS was confirmed by the detection of causative PTEN variants. Pathological examination of the polyps showed multiple histology types: hyperplastic, juvenile, serrated and lymphoid. Hyperplastic polyps analyzed from both patients failed to show BRAF V600E and KRAS codon 12/13 mutations, which provides evidence against their potential to evolve to colorectal cancer through the serrated pathway. We then reviewed the literature on gastrointestinal polyps detected in patients with Cowden Syndrome, in order to provide a comprehensive scenario of presentations: among a total of 568 patients reported in the literature, 91.7 % presented with colon polyps, with 63.0 % having two or more different histological types of polyps; besides, 58.5 % had extra-colonic polyps (located either in stomach and/or in small intestine). Finding multiple polyps with mixed and/or unusual histology should alert gastroenterologists and pathologists about the possible diagnosis of Cowden Syndrome and prompt the search for other manifestations of this condition in the patient., (Copyright © 2021 Elsevier GmbH. All rights reserved.)

Abstract: We report a case of pilomatrical tumor showing intermediate histological features between pilomatricoma and pilomatrical carcinoma. The lesion recurred twice with the same histological features. Similar cases were was probably called aggressive or proliferating pilomatixoma; we think that the term pilomatrical tumor of low malignant potential is more suitable for this lesions. Excision with wide free margins and follow-up are recommended., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Mycosis fungoides (MF) is defined as an epidermotropic primary cutaneous T-cell lymphoma composed of small-to-medium-sized T lymphocytes with cerebriform nuclei and with a T-helper phenotype. LeBoit first described an unusual variant of MF with dermal acid mucin deposition. Such a variant was still considered in the list of clinicopathological variants of MF by Cerroni and colleagues. We herein report a case of patch-stage MF with abundant papillary dermal mucin deposition in a clinical setting of an erythematous patch on the lower abdomen and thigh., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2021 by S. Karger AG, Basel.)

Introduction: For energy production, cancer cells maintain a high rate of glycolysis instead of oxidative phosphorylation converting glucose into lactic acid. This metabolic shift is useful to survive in unfavorable microenvironments. We investigated whether a positive glycolytic profile (PGP) in gastric adenocarcinomas may be associated with unfavorable outcomes under an anticancer systemic therapy, including the anti-angiogenic ramucirumab., Materials and Methods: Normal mucosa (NM) and primary tumor (PT) of 40 metastatic gastric adenocarcinomas patients who received second-line paclitaxel-ramucirumab (PR) were analyzed for mRNA expression of the following genes: HK-1, HK-2, PKM-2, LDH-A, and GLUT-1. Patients were categorized with PGP when at least a doubling of mRNA expression (PT vs. NM) in all glycolytic core enzymes (HK-1 or HK-2, PKM-2, LDH-A) was observed. PGP was also related to TP53 mutational status., Results: Mean LDH-A, HK-2, PKM-2 mRNA expression levels were significantly higher in PT compared with NM. 18 patients were classified as PGP, which was associated with significantly worse progression-free and overall survival times. No significant association was observed between PGP and clinical-pathologic features, including TP53 positive mutational status, in 28 samples., Conclusions: Glycolytic proficiency may negatively affect survival outcomes of metastatic gastric cancer patients treated with PR systemic therapy. TP53 mutational status alone does not seem to explain such a metabolic shift.

Background: Photodynamic antimicrobial chemotherapy (PACT) is an important therapeutic platform for antimicrobial activity, especially due to the resistant strains, however, the physical-chemical properties of the photosensitizers may affect the final outcome. Recently, this research group showed that the control of aggregation potentiates the PACT action of Methylene Blue. In this study, the researchers investigated the PACT action of other phenothiazinium dyes (PDs), such as Azure A, Azure B (AB), and 1,9-dimethyl methylene blue (DMMB), and the effects of different mediums which modulate PD aggregation were studied., Methods: The C. albicans planktonic culture was treated with PDs at different concentrations (0-100.00 mg/L), both in the dark (5 min) and irradiated (640 ± 12 nm LED during 30 min, 2.60 mW/cm 2 ). After the treatments, the diluted samples were grown on Sabouraud Dextrose Agar and maintained at 37 °C for 24 h. Later, one single concentration was defined and the inoculum was treated with the compounds in different media (water, phosphate buffer saline - PBS, physiological solution - 0.90 % NaCl, urea 1.00 mol/L, and sodium dodecyl sulfate 0.25 % - SDS), at 20.00 mg/L for AA and AB, and at 0.50 mg/L for DMMB. The cell uptake and the dimer to the monomer ratios were determined by spectrophotometry., Results: PACT with the PDs showed a reduction in the CFU/mL, with DMMB being the most effective due to the higher cell uptake within the series. When PACT was applied in the different mediums, the inactivation response was influenced by the medium. In water, the physiological solution, PBS, and urea showed no significant differences in relation to the control group. On the other hand, SDS potentiated the PACT action, and the inactivation of the microorganism was achieved with AB and DMMB., Conclusions: In water, DMMB presented the highest PACT action within the PDs being studied, reaching a microorganism inactivation with a 1.00 mg/L solution, mainly due to its high cell uptake. SDS 0.25 % increased the PACT action of the PDs studied, mainly with DMMB and AB, and this may be used in formulations to develop antimicrobial treatments to be used in clinics., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Introduction: Lung biopsy in asthmatic patients is justified in case of atypical presentations of asthma, when other differential diagnoses, such as hypersensitivity pneumonitis or eosinophilic granulomatosis with polyangiitis, could be possible or for research purposes., Aim: We aim to describe the utility and the safety of TBLC (transbronchial lung cryobiopsy) in asthmatic patients, providing data on the pathological changes occurring in the airways and in the lung parenchyma., Methods: We reviewed asthmatic patients that underwent TBLC, that eventually had only a final diagnosis of asthma., Results: Three patients were detected. TBLC described pathological abnormalities in peribronchiolar and alveolar spaces already well identified with SLB (surgical lung biopsy); the pathological information provided could be useful to better understand the pathobiology of the disease. Finally, we had no complications, confirming a satisfactory safety profile of TBLC., Conclusion: We suggest the potential role of TBLC in asthmatic patients: its safety and its acceptable diagnostic accuracy lead to consider this procedure instead of SLB when histological changes in lung parenchyma are needed for the differential diagnosis. Furthermore, TLBC could be useful for research in the pathobiology of asthma and severe asthma., Competing Interests: Since it is a retrospective analysis, no ethical committee approval was required.All patients gave the consent to treat their data anonimously.The authors declare that they have no competing interests. RP is a member of the Editorial Board of Multidisciplinary Respiratory Medicine.Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Competing Interests: Conflicts of Interest: Dr. Alessio Cortellini received honoraria as speaker at a scientific event from Boehringer-Ingelheim; the other authors have no conflicts of interest to declare.

Objectives: This study aimed to compare the interobserver Cohen κ on H&E staining and on H&E plus p16(INK4a) staining of all cervical biopsy specimens in a population-based screening program., Methods: All the colposcopy-guided biopsies generated by the routine screening of 23,258 women aged 25 to 64 years were stained with H&E and H&E plus p16. Biopsy specimens were reviewed by six external experts., Results: The four diagnoses were available in 441 cases. The interobserver κ values were 0.52 (95% confidence interval [CI], 0.45-0.58) and 0.48 (95% CI, 0.42-0.56) with H&E and H&E + p16, respectively, when using a five-group classification (normal, CIN 1, CIN 2, CIN 3, and cancer); adopting a two-group classification (≤CIN 1 and ≥CIN 2), the values were 0.75 (95% CI, 0.66-0.82) and 0.70 (95% CI, 0.61-0.79), respectively., Conclusions: The use of p16 on all cervical biopsy specimens in a screening program showed virtually no effect on reproducibility of the histologic diagnosis.

P16-INK4A overexpression has been proposed as a prognostic marker to manage the follow up of women with positive cytology and/or HPV test but without high-grade cervical intraepithelial neoplasia (CIN2+). This study measures the relative risk (RR) of CIN2+ of p16 positive versus negative in these women. All the women referred to colposcopy from October 2008 to September 2010 with negative or CIN1 colposcopy-guided biopsy were included in the study; women surgically treated or having a CIN2-3 were excluded. All baseline biopsies were dyed with hematoxylin and eosin and p16. Women were followed up according to screening protocols, with cytology or colposcopy at 6 or 12 months. CIN2/3 RRs and 95% confidence intervals (95%CI) were computed. Of 442 eligible women, 369 (83.5%) had at least one follow-up episode. At baseline, 113 (30.6%) were CIN1, 248 (67.2%) negative, and 8 (2.2%) inadequate histology; 293 (79.4%) were p16-negative, 64 (17.3%) p16 positive and 12 (3.2%) not valid. During follow up, we found ten CIN2 and three CIN3; of these, six were p16 positive (sensitivity 46%, 95% CI 19-75). The absolute risk among p16 positives was 9.4/100 compared to 1.7/100 of the p16 negatives (RR 5.5; 95% CI 1.7-17.4). The risk was also higher for CIN1 than for histologically negative women (RR 4.4; 95% CI 1.3-14.3). The RR for p16 in CIN1 did not change (RR 5.2; 95% CI 0.6-47.5). P16 overexpression is a good candidate for modulating follow-up intensity after a negative colposcopy but is limited by its low prospective sensitivity., (© 2013 UICC.)

This study compares colposcopy referrals of 2 management strategies: oncogenic human papillomavirus (HPV)-DNA testing (Hybrid Capture 2 assay, Qiagen, Germantown, MD) and repeat cytology. In the New Technology in Cervical Cancer Trial, 22,708 subjects were randomly assigned to undergo both HPV and liquid-based cytologic testing. Women aged 35 to 60 years old with unsatisfactory cytologic findings were directly referred for colposcopy if the HPV test result was positive, and were referred for repeat cytologic examination if the HPV test result was negative; women aged 25 to 35 years old were referred for repeat cytologic examination independent of HPV test results. A positive or a second unsatisfactory cytologic examination referred women for colposcopy. Five hundred sixty women had unsatisfactory cytologic findings. Colposcopy referral was not significant and slightly higher with HPV testing than repeat cytologic test (9.8% vs 6.8%, P = .11). When cytologic testing was repeated 36.8% were unavailable for follow-up and most of the colposcopies were performed in HPV-negative women. For unsatisfactory cytologic findings, HPV triage is a more logical and efficient management strategy than a repeat cytologic test.

To report on the diagnostic challenge of an adenoid cystic carcinoma arising from the eyelid. A 77-year-old male was referred to our center with a clinical diagnosis of upper eyelid chalazion for a lesion that had appeared 2 years before. A loss of cilia was observed over the cutaneous area of induration, but there was no reddening or ulceration. Incisional biopsy was performed and the specimen was submitted in formalin for histopathological examination. On light microscopy, the lesion was composed of basaloid epithelial and myoepithelial cells that were arranged in strands or nests and associated with cystic spaces that contained a deeply eosinophilic secretory substance and an Alcian blue-positive material, characteristic of adenoid cystic carcinoma. After histological diagnosis, tumor re-excision was performed to ensure adequacy of resection margins, as well as a sentinel lymph node procedure, resulting in complete excision of the malignant tumor. No recurrence was observed during the first 18 months after surgery. Adenoid cystic carcinoma is a rare and aggressive epithelial malignancy, which tends to grow slowly and should be considered in the differential diagnosis of eyelid tumors simulating chalazion.

Desmoplastic melanomas in an unusual variant of melanoma that usually occurs in sun-damaged skin of elderly people. Desmoplasia may be the prominent features of the lesion or represent a portion of an otherwise non-desmoplastic melanoma; these latter are called "combined" desmoplastic melanoma. Desmoplastic melanomas of the vulva are rare. Herein, we report a case of "combined" DM of the labia minor consisting of a superficial spitzoid component and a deeper spindle desmoplastic component. Protein S-100 expression was ubiquitous, while MART-1 and HMB-45 were limited to the superficial spitzoid component and were negative in desmoplastic areas. Notably, the nodal metastasis retained the same biphasic pattern seen in the primary tumour. The patient died of widespread metastatic disease 3 years after diagnosis.

Background: The difference in the diagnostic accuracy of 22- versus 25-gauge needles in EUS-FNA is not clear., Aims: To compare the rates of technical success, diagnostic accuracy and complications of EUS-FNA performed with 22-gauge and 25-gauge needles on the same solid pancreatic mass., Methods: All patients with solid pancreatic masses evaluated from September 2007 to December 2008 were enrolled and underwent EUS-FNA with both 22- and 25-gauge needles with randomisation of needle sequence. The accuracy of the EUS-FNA was determined by comparing the cytological results with the final surgical pathological diagnoses or with the results of a clinical follow-up. A cytological score with different qualitative parameters was created, and a comparison between these parameters was carried out for each needle., Results: Fifty patients with 50 pancreatic masses were recruited. Technical success was 100% and no complications occurred. Diagnostic accuracy was 94% and 86% for the 25- and 22-gauge needles, respectively. Analysis of the cytological score showed a tendency towards the 25-gauge needle, although the difference was not statistically significant., Conclusions: EUS-FNA performed with 22- or 25-gauge needles had the same diagnostic accuracy. Our study results confirm a significant trend towards a better cytological diagnosis for the 25-gauge needle., (Copyright © 2011 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

A case of skin metastases of prostatic ductal adenocarcinoma in a 78-year-old patient is reported. This case is characterized by two rare features: uncommon type of prostate carcinoma that metastatized to the skin.

The reproducibility of cervical histology diagnoses is critical for efficient screening and to evaluate the effectiveness of new technologies. The vast majority of cervical intraepithelial neoplasia (CIN) diagnoses reported in the New Technologies for Cervical Cancer study were blindly reviewed by 2 independent pathologists. Only H&E-stained slides were used for the review. The reviewers were asked to reclassify cases using the following categories: normal CIN 1, CIN 2, CIN 3, and squamous and glandular invasive cancer. We reviewed 1,003 cases. The interobserver agreement was 0.36 (95% confidence interval [CI], 0.32-0.40) with an unweighted kappa and 0.54 with a weighted kappa (95% CI, 0.50-0.58). The kappa values from dichotomous classifications with the threshold at CIN 2 were 0.69 (95% CI, 0.64-0.73) and 0.57 (95% CI, 0.51-0.63) with the threshold at CIN 3. The CIN 2 diagnosis had the lowest class-specific agreement, with fewer than 50% of cases confirmed by the panel members, which supports the fact that CIN 2 is not a well-defined stage in the pathogenesis of cervical neoplasia.

We report the case of a 27 year-old woman who had a pigmented lesion in her left leg in 2004. The lesion, which was diagnosed as a congenital compound nevus, recurred four years later as an obvious melanoma.

All cervical intraepithelial neoplasia (CIN) diagnoses identified during the New Technologies for Cervical Cancer trial (ISRCTN81678807) were blindly reviewed by 2 pathologists. Original diagnoses based on colposcopy-guided biopsies were compared with those made by the reviewers who had access to all clinical histologic samples (including postsurgical). Cases downgraded from CIN 2+ by the reviewers were considered indicative of unnecessary treatments. The analyses are presented according to the molecular (high-risk human papillomavirus [HPV]) and/or cytologic diagnosis used to refer the women for colposcopy. We reviewed 812 CIN 1 and 364 CIN 2 + diagnoses. The specificity of colposcopy-guided biopsy was 98% and the sensitivity, 84%. The probability of unnecessary treatment was 27% for women with atypical squamous cells of undetermined significance cytologic findings and 8% for women with low-grade squamous intraepithelial lesion or worse, 10% for HPV+ and positive cytologic findings, and 16% for HPV+ alone. The positive predictive value of the first-level screening test was inversely associated with probability of a histologic false-positive result (P = .015). In screening, a low positive predictive value of the colposcopy-referring test may result in unnecessary treatments.

Preoperative identification of the aggressive variants of papillary thyroid carcinoma (PTC) by fine needle aspiration (FNAC) has been suggested and different systems for distinguishing them from classical variant of PTC have been employed, including a point-based cytology grading system as suggested by Damiani et al., that we currently use in our Institution. The aim of this paper is to verify if distinction of PTC in aggressive or nonaggressive variants impacts on surgical treatment. In 7 years, from 1998 to 2005, 13586 cases of FNAC of thyroid have been performed; among them 156 PTC. The cytological material of thirty complete thyroidectomies with histology proven papillary thyroid carcinoma were reviewed. 11/30 cases were correctly stratified into the appropriate low or high-grade category. The cytological grading system was discordant with the final histopathological diagnosis in 9/30 cases while in 10 cases the grade was not assessed. Eight cases were downgraded and therefore the low grade papillary carcinoma diagnosed at cytological level turned to be high grade at histology. When those cases were reviewed, the histology of seven cases diagnosed as tall cell variant of PTC failed to show a percentage of tumour cells higher than 50% and therefore it would be better to diagnose them as classical variant of PTC. One case was under-graded at FNAC. The case that was cytologically upgraded was a follicular variant of PTC in Hashimoto thyroiditis with a focus of tall cells. All patients underwent thyroidectomy or thyroidectomy plus lymphadenectomy and from our results the pre-operative diagnosis did not effect the surgical treatment. No patient died of the disease.

A case of ganglioneuroma arising within a cystic mature teratoma of the ovary in a 34-year-old woman is reported. Patient underwent right adnexectomy. The ovary was completely replaced by a bilocular cystic lesion, measuring 8 cm in diameter and filled with adipose tissue and pilosebaceous material. Microscopically the cyst was composed by a mature cystic teratoma containing skin with dermal appendages, fatty tissue and bronchial epithelium. Furthermore a nodule (0.5 cm in size) composed of mature ganglion cells, axons and Schwann cells, was identified. Ganglion cells were positive for NSE and synaptophysin, while Schwann cells stained positively with S100 protein and GFAP. To the best of our knowledgment this is the first reported cases of ganglioneuroma arisen within a cystic mature teratoma of the ovary.

Malignant triton tumors (MTT) are rare soft-tissue tumors characterized by a mixture of cells with nerve sheath and skeletal muscle differentiation. MTT is a histological variant of malignant peripheral nerve sheath tumors (MPNST). No characteristic cytogenetic anomaly has been detected in MPNST or MTT. In this paper, we report on the cytogenetic findings of an MTT from a 20-year old male with neurofibromatosis (NF1). The tumoral karyotype showed the modal number to be near-diploid and an abnormal karyotype with a Robertsonian translocation and 4 markers: 49,XY,der(14;15)(q10;q10),+4mar. Spectral karyotyping revealed the karyotype: 49,XY, der(14;15)(q10;q10),+i(8)(q10)x4. Fluorescence in situ hybridization analysis of the tissue confirmed the presence of the additional i(8)(q10) in all tumoral cells. The sequence analysis of p53 revealed a polymorphism in exon 9, codon 329. The two alleles, TTC and TCC, codify for phenylalanine and serine, respectively. Our results indicate that all neoplastic cells have the same cytogenetic pattern, suggesting that both cell lines, which show nerve sheath and skeletal muscle differentiation, are derived from a unique stem cell. The acquired Robertsonian chromosomal recombinants might represent an event in the tumorigenesis of MTT, and the present data suggest that genes located on 8q can be involved in the development of MTT.

Background: The Tolosa-Hunt syndrome is characterized by ophthalmoplegia with unilateral severe retro-orbital pain associated to a granulomatous inflammatory process occupying the cavernous sinus or the superior orbital fissure. The etiology is unknown and diagnosis is based upon a clinical response to steroid treatment and exclusion of neoplasm, trauma, aneurysms, infectious, and inflammatory diseases., Case Description: A 43-year-old man was admitted because of a 1-week history of acute onset left-sided retro-orbital pain, followed by left sixth cranial nerve palsy. Magnetic resonance imaging was normal and Tolosa-Hunt syndrome was suspected. Steroid treatment controlled pain with recovery of ophthalmoplegia. Four months later, when a good response to treatment was still present, brain magnetic resonance imaging revealed a lesion enlarging the left cavernous sinus, isointense with the gray matter on T1-weighted sequences, hypointense on T2-weighted images, and with homogeneous enhancement after gadolinium injection. Two months later, ocular pain and sixth cranial nerve palsy recurred and new brain magnetic resonance imaging showed an extension of the tissue occupying the left cavernous sinus, over the sella, to the right cavernous sinus, making possible an endoscopic transphenoidal biopsy., Results: Histopathological study revealed a granulomatous aspecific inflammation containing actinomycetes colonies. The patient was treated with intravenous penicillin G followed by amoxicillin per os, with improvement of pain and ophthalmoplegia. A control magnetic resonance imaging 1 month after therapy showed a consistent reduction of the enlarged cavernous sinus, and 3 months later neurological examination and brain magnetic resonance imaging were completely normal., Conclusions: The present case suggests that the International Classification of Headache Disorders (2nd edition) definition of Tolosa-Hunt syndrome does not reflect the complexity of the syndrome and that some cases of secondary painful ophthalmoplegias can fit the criteria for the primary form. Since the biopsy can only rarely be performed, we agree with other authors that clinical and radiological follow-up should be performed for at least 2 years. Moreover, we propose that in patients with painful ophthalmoplegia having transient response to steroid therapy, a trial with antibiotic therapy should be taken into account.

The quality assurance scheme in use at the Section of Anatomic Pathology of the University of Bologna-Bellaria Hospital is described. Since 1992 a quality assurance (QA) scheme has been set up in this Institution. The scheme and results have been reported in this same Journal previously 1-3: here are reported the changes to the scheme that have intervened in the last four years. All data collected from January 1999 to December 2002 have been reviewed for monitoring the laboratory performance. Emphasis has been given to changes that have been introduced recently to improve QA.

A case of malignant transformation of a benign congenital hemangioma of the parotid gland is presented. The malignant tumor occurred in a woman with a history of congenital hemangioma surgically removed 8 years previously. No radiotherapy had been administered at the time of primary excision. The recurrent tumor consisted of a large lesion occupying nearly all the parotid gland and infiltrating the surrounding soft tissues and overlying skin. Its histopathologic features were typical of epithelioid angiosarcoma. The vast majority of vascular lesions of major salivary glands are benign. However, pathologists should be aware of the remote possibility of malignant transformation in these lesions.

Histoplasmosis, which is highly endemic in the United States, is rare in Europe, usually imported but sometimes autochthonous. In Africa, histoplasmosis capsulati coexists with "African histoplasmosis", a characteristic skin infection caused by H. capsulatum var. duboisii. Histoplamosis due to H. capsulatum is one of the 12 secondary infections listed in the surveillance definitions of AIDS. We report the case of a 36-year-old black man with acquired immunodeficiency syndrome (AIDS) who was living in Italy but originally came from Ghana. Histoplasmosis was disseminated with fever and cutaneous manifestations. The diagnosis was demonstrated morphologically based on the presence of yeast, observed by light microscopy, in skin lesions and by identification of H. capsulatum var. capsulatum DNA by nested PCR from a paraffin sample. No clinical reports of histoplamosis capsulati in Ghana have been published until now. The present case stresses the role of immigration of subjects from outside Europe who have been infected in their native country.

Three (propositus) cases of basal cell carcinoma (BCC) showing endocrine differentiation at the immunohistochemical level were studied using reverse transcriptase-polymerase chain reaction (RT-PCR) to determine the presence of mRNA of chromogranin A. Moreover, 20 (consecutive) cases of BCC were studied with immunohistochemistry alone using chromogranin A, synaptophysin, S100 protein, cytokeratin 20, and neuron-specific enolase antibodies (NSE). The three propositus cases of BCC showed positive results when RT-PCR for mRNA of chromogranin A was performed. Eleven out of 20 consecutive cases of BCC were focally positive for chromogranin A antibody. These results confirm the presence of endocrine differentiation in BCC, demonstrated both with immunohistochemistry and with RT-PCR.

Neuroblastoma are pediatric tumors of neural crest origin, most often localized in adrenal glands and infrequently congenital. We report two fetal cases found at autopsy, performed at 24 and 28 weeks of gestation, respectively. The 24 week old fetus did not show any malformation; systematic histological analysis found neuroblastoma cells in both the adrenal glands and the retroperitoneal fat tissue. The 28 week old fetus was hydropic and exhibited a nodule (3 cm) in the posterior mediastinum, next to the thoracic spinal cord. This tumor responded to a neuroblastoma associated with small metastatic foci in the adrenal glands, the liver and the frontal brain cortex. The placenta was abnormally heavy and showed hemorrhagic and necrotic areas. Microscopically plugged clumps of neuroblastoma cells were found inside fetal vessels. Immunohistochemistry was employed in both cases and the cells showed immunoreactivity for NSE, NB 84, chromogranin, synaptophysin and neurofilaments, while desmin, MIC 2, and protein S-100 were negative. Congenital neuroblastomas are rare and, to our knowledge this is the thirteenth report of congenital neuroblastoma associated with placental metastasis.

We describe two cases of adult rhabdomyoma. One was located in the lip of a 66-year-old woman and was removed because it was clinically suspicious for infiltrating carcinoma. The other arose in the eyelid of a 60-year-old woman with a glass eye and was initially interpreted as a reactive process due to the prosthesis. Both lesions were composed of cells with oval nuclei and deeply eosinophilic cytoplasms with occasional cross striations. Immunoreactivity for desmin and myoglobin excluded the diagnosis of other tumors with similar morphology. The unusual association of the eyelid tumor with the prosthesis suggests a role for chronic irritation in the pathogenesis of rhabdomyoma.

A case of hyperkeratosis follicularis et parafollicularis in cutem penetrans Kyrle's disease in a 41-year-old woman is described. It was a recurrence of a lesion surgically removed and originally diagnosed as invasive squamous cell carcinoma. Kyrle's disease is a rare dermatosis and should not be confused with neoplastic conditions i.e. squamous cell carcinoma. Pathologists should be aware of such conditions in order to avoid misdiagnosis, which can imply over treatment for the patient.

We report three cases of desmoplastic malignant melanoma (DMM) rich in smooth muscle actin. They occurred in two men (Cases 1 and 3) and in one woman (Case 2). Cases 1 and 2 were recurrent lesions from common melanomas excised, respectively, 3 and 1 years previously. In Case 3, DMM was associated with lentigo maligna at the time of presentation. Morphologically, DMMs were composed of spindle neoplastic cells organized in haphazardly orientated long fascicles separated by collagen bundles. Perineural invasion was present and mitotic activity was prominent in all cases. The neoplastic spindle cells were intensely positive with S100 protein and smooth muscle actin antisera and negative with HMB45 and Melan-A (Mart-1) antibodies. Double staining for smooth muscle actin and S100 protein revealed no definite coexpression of the two antigens. Follow-up was available for patients 1 and 2 who had local recurrences and are still alive. It is possible that actin rich elements differentiate toward mesenchymal elements, paralleling the phenotypic changes seen in sarcomatoid carcinomas. Therefore, multidirectional differentiation may explain the mesenchymal (sarcomatoid) differentiation of neoplastic melanocytes and may be responsible for the different biologic behavior of DMMs, which is closer to mesenchymal tumors than to conventional melanomas.

The quality control scheme in use at the Department of Anatomic Pathology of the University of Bologna-Bellaria Hospital Since 1993 a quality assurance (QA) scheme has been set up in our Department, modified from the protocol in use at the Department of Pathology of Yale University and published by J. Rosai in his textbook. A QA committee has been appointed and each member is responsible for a specific branch of the total workload; the areas involved are: 1. review of frozen section diagnoses with the final diagnoses 2. randomized review of biopsies (1:25) 3. quality control of cytological cases 4. quality control of specimen adequacy 5. quality control of immunohistochemistry and in situ Hybridization 6. quality control of the cytogenetics laboratory 7. quality control of autopsies All data collected from january 1996 to february 1999 have been reviewed and analyzed in order to provide references for other laboratories and for the purpose of monitoring our laboratory' performance.

Four cases of trichoblastoma rich in Merkel cells (MCs) are reported. They occurred in two men and two women, with ages ranging from 58 to 76 years (mean 67.5 years). MCs were detected immunohistochemically with antibodies to keratin 20, chromogranin A and neuron-specific enolase (NSE). In an attempt at better definition of the nature and role of MCs in trichoblastoma, the distribution of MCs in normal adult and fetal skins obtained at autopsy was studied. In addition, ten cases of sebaceous naevus of Jadassohn (NSJ) were evaluated along similar lines. MCs made up 2-20% of the tumour cells in trichoblastomas; they were present in normal fetal skin and were rare in normal adult skin. All but one of the cases of NSJ showed numerous positive cells in the epidermal component of the lesion with all three antibodies. Six basal cell carcinomas and one syringocystadenoma papilliferum associated with NSJ were negative with keratin 20, chromogranin A and NSE antibodies, whereas a minute trichoblastoma arising against the same background was positive for these markers. Hair follicle cell tumours may recapitulate the skin embryogenesis, as numerous MCs are present in fetal follicles, but only occasional such cells are seen in adult skin.

Pseudoepitheliomatous hyperplasia or pseudocarcinomatous hyperplasia (PEH) is characterized by a downward expansion of the epidermis, which can simulate a squamous cell carcinoma (SC). It is usually associated to chronic inflammatory conditions, but rarely it can hide a tumour. In the present paper a case of melanoma (M) associated with a prominent PEH is described. The patient is a 79-year old woman who presented a polypoid, ulcerated lesion of the left thigh. The lesion was entirely removed. The patient is free of disease 5-years after surgery. On histology, the malignant melanomatous proliferation was closely admixed to sheets of squamous cells. The possibility of SC was excluded as the squamous component did not show architectural disarray, prominent nucleoli and atypical mitoses. Siringomatous metaplasia was observed in the deeper portion of the lesion. On the basis of these findings the diagnosis of melanoma (M) associated to prominent PEH was considered the most likely.

We report a case of neuroendocrine (Merkel cell) carcinoma (NC) of the skin, associated with a trichilemmal cyst, showing pagetoid spread into the trichilemmal epithelium. The association of the two lesions may strengthen the hypothesis that NC originates from pluripotent stem cells of adnexal epithelium.

We report a case of syringoid eccrine carcinoma, a rare syringomatous tumor of the skin, occurring in a 70-year-old woman. Histological and immunohistochemical criteria are given to differentiate this neoplasm from other primary carcinomas of the skin as well as from skin metastases of internal malignancies.

The occurrence of human herpes virus type 8 (HHV-8) DNA sequences was evaluated by polymerase chain reaction in 36 cases of cutaneous Kaposi's sarcoma (KS) (classic and associated with the acquired immunodeficiency syndrome) and in 88 pathologic entities that can histologically mimic KS, such as reactive and neoplastic vascular processes and lesions featuring focal or extensive spindle cell pattern. A positive reaction was detected in 16 (70%) of 23 samples of classic KS and 10 (77%) of 13 KS cases related to the acquired immunodeficiency syndrome. In particular, 4 (50%) of 8 samples in the patch stage were found to be positive, whereas in the plaque and nodular stages, HHV-8 DNA sequences were observed in 8 (67%) of 12 and 14 (87%) of 16 cases, respectively. KS cases that had yielded previous negative results were found to be positive for HHV-8 on nested polymerase chain reaction, except two cases of classic KS in the patch stage (6% of the total number of KS, 25% of cases in the patch stage). Reactive and neoplastic vascular processes and cutaneous lesions with a spindle cell component were consistently negative. HHV-8 detection by polymerase chain reaction can represent a valuable method for diagnosing KS, particularly in small skin biopsy samples that might show histologic overlap with non-KS lesions. In early patch stage lesions, however, the diagnostic value of the method is hampered by the occurrence of cases in which HHV-8 sequences are still undetectable.

The frequency and distribution of herpesvirus-like DNA sequences (KSHV) were investigated by PCR in the pathologic skin lesions of a series of 22 HIV-negative elderly patients with classic Kaposi's sarcoma (KS) from Italy, one of the few regions of the world where classic KS is prevalent. Viral sequences were clearly identifiable in 15 cases, in particular in 2 of 5 patch, in 3 of 6 plaque and in 10 of 11 nodular lesions. Our findings confirm the association of these herpesvirus-like DNA sequences with KS in unrelated populations, providing evidence of the putative KS-associated agent in all different histologic lesions of the disease, mainly in the nodular stage. The search for other herpesviruses by PCR showed that Epstein-Barr virus (EBV) sequences were present in 7 of 22 pathologic skin lesions. In 4 cases, both EBV and KSHV were present. On the contrary, all 22 classic KS specimens were negative for human herpesvirus-6 sequences. Two of 3 patch and the 1 nodular lesions from AIDS-related KS patients examined were positive for KSHV but negative for both EBV and HHV-6 sequences. Furthermore, we evaluated the prevalence of KSHV sequences in the normal population of the same geographical area. Thirteen peripheral blood mononuclear cell samples, 9 salivary gland tissues and 6 saliva samples from healthy subjects were invariably found negative for KSHV, using the same PCR technique. Of interest, 2 of 11 hyperplastic tonsils harboured these herpesvirus-like sequences, suggesting that, like other herpesviruses, the KS- associated agent may be harboured in a proportion of normal individuals and tonsils may represent at least one of the possible reservoirs of this putative lymphotropic gamma-herpesvirus in vivo.

A chordoma metastatic to the skin of the nose is reported. The patient (a 40-year-old man) had undergone excision of a sacral chordoma 16 months previously. In patients whose clinical histories are unknown, cutaneous metastases of chordoma can be confused with mixed tumors of sweat glands. Cytological features, including the presence of physaliphorous cells, and immunohistochemical coexpression of low molecular weight keratins and S-100 protein are helpful features that lead to a correct diagnosis.

Unlabelled: Two cases of breast carcinoma metastatic to meningioma are described in patients 69 and 62 years old respectively., Material and Methods: Cases were documented by radiological, histological and immunohistochemical techniques., Results: Both meningiomas contained an invasive duct carcinoma of the breast, one of which was apocrine in nature., Conclusion: It is suggested that metastasis to meningioma is not so rare as it appears from the literature.

Expression of the major histocompatibility (MHC) class I and class II antigens was studied by immunohistochemistry in a series of 70 primary breast carcinomas and in nodal metastases. In particular, the expression of class I (HLA A-B-C) and class II (DP, DQ and DR) molecules was compared in: a) primary breast cancers devoid of nodal metastases (n = 36) and tumors exhibiting metastatic deposits (n = 34) at the time of surgery, and b) primary breast carcinomas and their corresponding synchronous axillary nodal metastases. Reduced or absent HLA A-B-C antigen expression was seen in approximately 54.3% of primary breast carcinomas, whereas a partial or complete induction of class II products was observed in 18.5% (DQ), 30% (DP) or 48.5% (DR) of the same cases. An almost complete overlap of antigen expression was observed in breast tumors in which no metastases were found by histological examination of axillary nodes and in neoplasms showing histologically-diagnosed synchronous metastases. The reactivity for class I and class II antigens in nodal metastases roughly paralleled that exhibited by corresponding primary tumors. A discordant expression was seen in 11 cases (32%) stained for HLA A-B-C and in 8 (24%), 7 (21%) and 6 (18%) cases assayed for DP, DQ and DR products, respectively. When a discordant expression was detected, either decreased or increased staining patterns were observed in metastases. The finding of overlapping MHC antigenic profiles in the majority of primary breast tumors and nodal metastases casts doubts on the hypothesis that loss of MHC antigens can play an important role in the seeding and growth of metastatic breast carcinoma cells.

Pleomorphic adenoma (PA) is the commonest tumor of salivary glands. It is considered a benign tumor which may recur and rarely metastatize. There are no reliable histological criteria for predicting recurrences of PA. In this paper, Ag-NOR expression, evaluated by means a computer assisted image analysis system, has been tested on 11 cases of PA, their recurrences, 10 non recurrent PA and 5 cases of carcinoma ex PA. Mean AgNOR count, mean AgNOR area and mean AgNOR area/particle were determined in each group. AgNOR count and area did not show any significant differences between recurrent and non recurrent PA. On the contrary, AgNOR area/particle seems to be a useful tool in predicting the clinical behaviour of this lesion.

We reviewed 391 cases of salivary gland tumors collected in a 13 year period at the Institute of Pathological Anatomy of the University of Modena, according to the new WHO classification (1991). A diagnosis of pleomorphic adenoma was changed in adenoid cystic carcinoma. Within malignant tumors, 16 cases were reclassified, and new entities, such as polymorphous low-grade adenocarcinoma, papillary cystoadenocarcinoma and salivary duct carcinoma were introduced. Mucoepidermoid carcinomas were subdivised in low-grade and high-grade tumors, but at the follow-up histological grade did not correlate with clinical behaviour of the lesions.

We report a case of a medullary carcinoma of the left lobe of the thyroid gland that occurred in a 57-year-old woman. The patient had undergone surgery for treatment of a bilateral-functioning pheochromocytoma when she was 39 years old. A medullary carcinoma of the thyroid gland and/or a pheochromocytoma had also been diagnosed in other family members. The tumor was composed of cells arranged in nests and large sheets separated by fibrous stroma that contained amyloid deposits. Elongated cells with thin, branched cytoplasmic projections that were strongly reminiscent of sustentacular cells usually found in paragangliomas were seen among the neoplastic cells. Immunohistochemical study showed a diffuse positive reaction for calcitonin and low-weight keratins (CAM 5.2) in neoplastic cells, whereas the sustentacular cell-like cells were positive for S100 protein. The reaction for thyroglobulin was negative. Electron microscopy disclosed large numbers of typical neurosecretory granules in the cytoplasm of tumor cells. The sustentacular cell-like cells showed elongated cytoplasmic processes and lacked neurosecretory granules. We concluded that the finding of sustentacular cell-like cells in a medullary carcinoma of the thyroid gland made its differential diagnosis from paraganglioma more problematic.