Glomus coccygeum: a review.

With limited information about the coccygeal glomus found in classic textbooks, we deemed it necessary to review the subject. The illustrations presented in this article derive from four coccygeal glomera incidentally encountered during examination of pilonidal disease specimens. Familiarization with its microanatomical features may help to avoid inappropriate interpretation of this enigmatic structure.

Value of real-time gastric juice analysis in upper gastrointestinal endoscopy.

AIM: Esophagogastroduodenoscopy (EGDS) cannot identify microscopic lesions. We determined the contribution of real-time gastric juice analysis in detecting lesions non-detectable with the simple endoscopic inspection. METHODS: Endoscopy, histology and gastric juice analysis were performed in 216 patients. We assessed six diagnostic strategies: EGDS (strategy-1), EGDS with antral biopsies (hematoxylin-eosin staining) in hypochlorhydrics (strategy-2) or all patients (strategy-3), EGDS with antral and fundic biopsies (hematoxylin-eosin staining) in hypochlorhydrics (strategy-4) or all patients (strategy-5), EGDS with antral and fundic biopsies (hematoxylin-eosin + immunohistochemical staining) in hypochlorhydrics (strategy-6). Then, we determined how many of the pathological conditions identified by the complete histological evaluation would have been detected by each strategy. RESULTS: In total, 220 pathological conditions were identified. Hypochlorhydria was correlated (r=0.67; P<0.01) with histological lesions (85% lesions were detected in hypochlorhydrics) and high ammonium levels, with H.pylori infection (r=0.69; P<0.01). Strategy-1 identified only 5% conditions, while strategies 3 and 5 detected 68.6% and 83.2% conditions, respectively. Strategies 2, 4 and 6 (based on gastric juice analysis) yielded detection rates (61.4%, 75.5%, 90.9%) similar to or better than those of strategies 3 and 5. CONCLUSION: Real-time gastric juice analysis provided information about the presence of gastric lesions in an otherwise "normal" stomach at EGDS. It improved the diagnostic yield and optimized resource utilization without any additional effort by the endoscopist.

Perendoscopic real-time assessment of pH improves detection of gastric preneoplastic conditions.

AIM: Gastric juice may constitute a precious source of clinicopathological information. We assessed the usefulness of real-time, perendoscopic, gastric juice pH determination in identifying preneoplastic conditions of the stomach, that often escape the mere endoscopic evaluation. METHODS: The study included 245 patients (115M; 130F; age 47±17). In each of them perendoscopic gastric juice pH was assessed by means of an innovative device, the Endofaster, and the results were correlated with histological evaluation (H&E, immunohistochemistry, argyrophil stains), and gastric acid secretion (BAO-PAO), and serum gastrin levels. The conditions evaluated were: atrophy, intestinal metaplasia, endocrine cell hyperplasia, hypergastrinemia. RESULTS: A total of 136 pathological conditions were detected and these resulted to be correlated with pH (r=0.67; P<0.01). The rate of pathological conditions was low in normochlorhydric patients (14.1%); most of these conditions were concentrated in patients with hypochlorhydria (85.9%) (P<0.001). Specifically, the number of patients with one or more pathological conditions increased proportionately with the rise in pH levels. An inverse correlation was detected between gastric juice pH and basal acid output (BAO) (r=-0.72; P<0.01). Endoscopic feature was normal/mild in most of patients with pathological conditions. CONCLUSION: Hypochlorhydria is a sensitive indicator of gastric risk conditions. Perendoscopic real-time assessment of pH can improve and extend optical analysis by allowing the detection of pathological conditions (either preneoplastic or not) that often escape diagnosis because not correlated with specific endoscopic pattern.

Muscle spindle and Pacinian corpuscle: conceptions, misconceptions, and the far-fetched hypothesis of an experienced surgical pathologist.

The muscle or neuromuscular spindle is a proprioceptive microanatomic structure, which together with the Golgi tendon organ, is responsible for the reflex are that determines the tonic state of muscle. The Pacinian corpuscle (or corpuscle of Vater-Pacini) is a pure mechanoreceptor, sensitive to pressure, typically found in the skin, subcutis and superficial soft tissues. Generally, both the muscle spindle and Pacinian corpuscle are microanatomical findings that are too unremarkable to focus on during the course of routine work in surgical pathology. We recently encountered such a structure, which required full attention to be correctly identified: the incidental finding was a curious muscle spindle, the "fibrous capsule" of which mimicked the "lamellar body" of Pacinian corpuscle. This report accurately mirrors the manner in which the events occurred and emphasizes the fundamental anatomical notions that were ignored, and is also an opportunity to mention some of the pathological conditions affecting the aforementioned often-neglected receptors.

Subcutaneous Ewing sarcoma/PNET as a second cancer in a previously irradiated young patient. an uncommon type of post-irradiation soft tissue sarcoma.

Soft tissue sarcomas account for a small proportion of second cancers, with an estimated frequency of < 10%. The most common histologic type of soft tissue sarcomas as second cancers include mostly high-grade sarcomas, such as rhabdomyosarcoma, malignant peripheral nerve sheath tumour, fibrosarcoma, leiomyosarcoma, synovial sarcoma, alveolar soft part sarcoma and Ewing sarcoma/primitive neuroectodermal tumour (PNET). We report a case of superficial soft tissue Ewing sarcoma/PNET as a second cancer in a young patient previously treated for Hodgkin's disease (HD). To the best of our knowledge and based on a literature search, this is the first reported case of post-irradiation soft tissue Ewing sarcoma/PNET as a second cancer arising in the same area irradiated for cure of HD.

Atypical dermatofibroma with predominant epithelioid/deciduoid-like cell component. Histogenetic considerations in the wide spectrum of fibrohistiocytic dermal tumours.

Atypical and epithelioid cell variants of dermatofibroma may represent a potential diagnostic pitfall. Only rarely atypical dermatofibroma may show focal epithelioid cell features. We herein report a rare case of dermatofibroma composed of a predominant (> 90%) epithelioid/deciduoid-like cell component, in which rare multinucleated bizarre cells and atypical mitoses were additional findings. Tumour was classified as "atypical dermatofibroma with predominant epithelioid/deciduoid-like cell component". The coexistence of at least two different variants, i.e. epithelioid and atypical variants, in the same dermatofibroma suggests that dermal fibrohistiocytic tumours belong to a continuous morphological spectrum. Accordingly, the morphological variants of dermatofibroma should be regarded as variations on a common basic theme. Differential diagnosis with other epitheliod cell dermal tumour- and tumour-like lesions is discussed.

Successful treatment of Schnitzler's syndrome with anakinra after failure of rituximab trial.

We report a 50-year-old man who presented with a 5-year history of an intermittent widespread pruritic urticarioid rash and fever, fatigue, arthralgia and a monoclonal immunoglobulin-M paraprotein. The patient was initially treated with antihistamines and corticosteroids without the disappearance of symptoms. A skin biopsy from the urticarial rash on the thorax was performed, revealing dermal mononuclear and polymorphonuclear cell infiltrate and normal epidermis. A diagnosis of Schnitzler's syndrome (SS), a rare disorder in which the simultaneous occurrence of monoclonal gammopathy and chronic urticaria is usually observed, was made. After an unsuccessful trial with rituximab at a dosage of 375 mg/sqm weekly for 4 consecutive weeks, the patient was treated with anakinra, an inhibitor of interleukin-1alpha that is thought to be involved in the pathogenesis of the disease, at a dose of 100 mg daily given subcutaneously. He showed a prompt response to the drug and he is still well and symptom-free after 12 months of follow-up. On the basis of both this experience and the review of the literature we conclude that anakinra may be a promising option for the treatment of SS. However, these results need to be confirmed on a larger number of patients.

Differential expression of microRNAs in human parathyroid carcinomas compared with normal parathyroid tissue.

Parathyroid carcinoma (PaC) is a rare cause of primary hyperparathyroidism. Though the loss of the oncosuppressor CDC73/HRPT2 gene product, parafibromin, has been involved in the hyperparathyroidism-jaw tumor syndrome and in a consistent set of sporadic PaCs, parathyroid carcinogenesis remains obscure. MicroRNAs are a new class of small, non-coding RNAs implicated in development of cancer, since their deregulation can induce aberrant expression of several target genes. The aim of the present study was to identify differentially expressed microRNAs in parathyroid cancers compared with normal tissues. We performed a TaqMan low-density array profiling of four parathyroid cancers harboring CDC73 inactivating mutations and negative for parafibromin immunostaining. Their microRNA profiling was compared with that of two normal parathyroid biopsies. Out of 362 human microRNAs assayed, 279 (77%) were successfully amplified. Fourteen and three microRNAs were significantly down- and over-expressed in parathyroid cancers respectively. Of these, miR-296 and miR-139 were down-regulated, and miR-503 and miR-222 were over-expressed with a null false discovery rate. Carcinomas could be discriminated from parathyroid adenomas by a computed score based on the expression levels of miR-296, miR-222, and miR-503 as miR-139 was similarly down-regulated in both cancers and adenomas. Finally, miR-296 and miR-222 levels negatively correlated with mRNA levels of the hepatocyte growth factor receptor-regulated tyrosine kinase substrate and p27/kip1 levels respectively. These results suggest the existence of an altered microRNA expression pattern in PaCs together with a potential role of miR-296 as novel oncosuppressor gene in these neoplasia.

The effect of prebiotics in the management of neonatal hyperbilirubinaemia.

BACKGROUND: Breast milk oligosaccharides such as galacto-oligosaccharides (scGOS) and fructo-oligosaccharides (lcFOS) can influence the intestinal microbial flora. The latter, in turn, can modulate several intestinal and extraintestinal functions, including bilirubin metabolism. Supplementing infant formula with a prebiotic mixture might then be a novel and safe intervention to manage mild neonatal hyperbilirubinaemia. AIM: To investigate the effect of dietary supplementation with prebiotics on moderate hyperbilirubinaemia in healthy, term infants. METHODS: A prospective, double-blind, clinical trial was performed on seventy-six consecutive newborns who were randomly assigned to receive a formula containing 0.8 g/dL of a mixture from scGOS and lcFOS (ratio 9:1), or maltodextrines as placebo for 28 days. Bilirubin levels were determined by the transcutaneous bilirubin measurement within 2 h after birth (T1), at 24, 48 and 72 h and at 5, 7, 10 and 28 days of life. The number of stool per day was also recorded. RESULTS: Neonates receiving prebiotics showed a larger number of stools over all the duration of dietary intervention compared to that of those on placebo (Repeated Measures ANOVA p < 0.001; day 28 3.4 +/- 0.0.9 vs 1.7 +/- 0.9, respectively; Dunn test p < 0.05). Neonates whose formula was supplemented with prebiotics showed a lower transcutaneous bilirubin that was statistically significant from 72 h of life (5.46 +/- 1.6 vs 7.07 +/- 2.49, post hoc Dunn test, p < 0.05) throughout the duration of the dietary intervention (day 28 2.41 +/- 0.4 vs 2.85 +/- 0.5, post hoc Dunn test, p < 0.05). CONCLUSION: The addition of prebiotics to standard infant diet might represent a novel strategy to help control neonatal hyperbilirubinaemia.

Pleomorphic hyalinizing angiectatic tumor of the male breast: a heretofore unreported occurrence.

Pleomorphic hyalinizing angiectatic tumor (PHAT) is considered an unusual mesenchymal tumor of intermediate malignant potential that is distinguished by a prominent angiectatic vasculature with clusters of thin-walled, fibrin-lined vessels surrounded by sheets of spindled and pleomorphic cells. This lesion occurs mostly in the subcutaneous soft tissues of the lower extremities. In this paper, the authors report the first case of PHAT involving the breast parenchyma of a 75-year-old man. The patient was referred to the hospital with a history of a painless left breast mass that had been growing for several years. The lesion did not recur after surgery. The tumor exhibited histopathologic and immunohistochemical features identical to those of a PHAT of other sites. The purpose of this report is to add a rare tumor to the differential diagnosis of mammary spindle cell neoplasms.

Effects of probiotic and prebiotic on gastrointestinal motility in newborns.

To fortify the biological role of milk formula has been suggested to use probiotics and prebiotics as functional components to mimic the effect of breast milk. The aim of this study was to evaluate the effects of prebiotic, probiotic added to a standard formula on gastrointestinal motility respect to placebo-formula. Cutaneous electrogastrography (EGG) and ultrasound gastric emptying (GE) were performed in 49 preterm newborns. 17 newborns were exclusively breast-fed; 32 were randomly assigned to receive prebiotic-added formula (0.8 g/dl of a mixture from scGOS and lcFOS, ratio 9:1) (10), a probiotic-added formula (L. reuteri at dose of 1x10(8) colony forming units (CFU) per day) (10), a formula with placebo (12) for 30 days. No difference was seen in the nutritional parameters and no adverse events were reported. After the intervention period, the prebiotic, probiotic, and breast milk groups showed a higher percentage of EGG slow wave propagation and faster gastric half emptying time respect to placebo group (ANOVAon ranks p<0.001; Dunn test vs control: prebiotic, probiotic and breast-milk vs placebo formula p<0.05; and ANOVA on ranks p=0.005; Dunn test vs control: prebiotic, probiotic and breast-milk vs placebo formula p<0.05, respectively). Feeding preterm infants with a formula supplemented with prebiotics or probiotics may stimulate gastric emptying and improve maturation of the EGG activity mimicking the effect of breast milk.

Use of natural surfactant in an infant with aspiration syndrome.

The remarkable effectiveness of surfactant in neonatology suggested its use also in adults as well as in children on the basis of the pulmonary pathophysiology. We describe a case of an 18 month-old child affected by acute respiratory distress syndrome (ARDS) due to asphyxy by gastric juice inhalation, successfully treated with porcine surfactant (Curosurf) associated with ventilatory therapy.

A comparison of nasal intermittent versus continuous positive pressure delivery for the treatment of moderate respiratory syndrome in preterm infants.

AIM: Nasal continuous positive airway pressure and nasal intermittent positive pressure ventilation have both been proposed as a form of gentle respiratory support for neonatal respiratory distress syndrome. We have compared these two respiratory support methods in the management of early stages of mild-moderate, neonatal respiratory distress syndrome. METHODS: A prospective, randomized trial was performed enrolling 88 consecutive preterm infants with mild to moderate respiratory distress syndrome matched for birthweight, gestational age, sex, admission FiO2 and Apgar scores. Nasal continuous positive airway pressure was delivered at a pressure of 4-6 cmH2O. Infants on intermittent pressure were put on ventilatory rates of 40 breaths per minute. Peak pressures of 14-20 cmH2O and end-expiratory pressures of 4-6 cmH2O were used judging clinically the chest cage expansion. RESULTS: Although there were no differences in the PaO2 values between the groups, infants treated with nasal intermittent positive pressure ventilation showed a significantly lower pCO2 values than those in the continuous pressure group (40+/-2 vs 58+/-4 mmHg, P<0.05). Also a significantly lower incidence of apnoeic episodes (number of episodes/hour 0.4+/-0.2 vs 0.9+/-03; P<0.05) and a shorter respiratory support in the nasal intermittent positive pressure ventilation group were observed. No difference in severe abdominal distension or need of endotracheal intubation was noted. CONCLUSIONS: In the present clinical setting, the use of nasal positive airway pressure in an intermittent way is associated to a more physiological arterial carbon dioxide tension, less apnoea and a shorter duration of respiratory support when compared with continuous pressure delivery by the same route.

Myeloid sarcoma: clinico-pathologic, phenotypic and cytogenetic analysis of 92 adult patients.

Myeloid sarcoma (MS) is a rare neoplasm whose knowledge is largely based on case reports and/or technically dated contributions. Ninety-two MSs in adulthood with clinical data available were evaluated both morphologically and immunohistochemically. Seventy-four cases were also studied by fluorescent in situ hybridization on tissue sections and/or conventional karyotyping on bone marrow or peripheral blood. Histologically, 50% of the tumors were of the blastic type, 43.5% either monoblastic or myelomonocytic and 6.5% corresponded to different histotypes. CD68/KP1 was the most commonly expressed marker (100%), followed by myeloperoxidase (83.6%), CD117 (80.4%), CD99 (54.3%), CD68/PG-M1 (51%), CD34 (43.4%), terminal-deoxy-nucleotidyl-transferase (31.5%), CD56 (13%), CD61/linker for activation of T cells (2.2%), CD30 (2.2%) and CD4 (1.1%). Foci of plasmacytoid monocyte differentiation were observed in intestinal cases carrying inv16. Chromosomal aberrations were detected in about 54% of cases: monosomy 7(10.8%), trisomy 8(10.4%) and mixed lineage leukemia-splitting (8.5%) were the commonest abnormalities, whereas t(8;21) was rare (2.2%). The behavior was dramatic irrespective of presentation, age, sex, phenotype and cytogenetics. Most if not all, long survivors received bone-marrow transplantation. The present report expands the spectrum of our knowledge showing that MS has frequent monoblastic/myelomonocytic differentiation, displays distinctive phenotypic profile, carries chromosomal aberrations other than t(8;21), and requires supra-maximal therapy.

Tumoral, quasitumoral and pseudotumoral lesions of the superficial and somatic soft tissue: new entities and new variants of old entities recorded during the last 25 years. Part XII: appendix.

In an eleven part series published in Pathologica, we have presented various tumoral, quasitumoral and pseudotumoral lesions of the superficial and somatic soft tissue (ST), which emerged as new entities or as variants of established entities during the last quarter of a century. Detailed clinicomorphological and differential diagnostic features of approximately sixty entities were chosen on the basis of their clinical significance and morphologic distinctiveness. The series included fibrous and myofibroblastic tumors (e.g. solitary fibrous tumor, high grade classic and pigmented dermatofibrosarcoma protuberans, inflammatory myofibroblastic tumor and myofibrosarcomas), fibromyxoid and fibrohistiocytic neoplasms (e.g., Evans' tumor, phosphaturic mesenchymal tumor, inflammatory myxohyaline tumor), special adipocytic/vascular/and smooth muscle lesions (e.g., chondroid lipoma, Dabska's tumor, ST hemangioblastoma, lipoleiomyosarcoma), epithelioid mesenchymal malignancies of diverse lineages (e.g., epithelioid liposarcoma, proximal-type epithelioid sarcoma, neuroendocrine extraskeletal chondromyxoid sarcoma), ST Ewing's tumor and peripheral nerve sheath tumors (perineuriomas and pigmented and rosetting tumors of the schwannoma/neurofibroma group), extranodal dendritic or histiocytic proliferative processes (follicular dendritic cell sarcoma, Rosai-Dorfman disease, Castleman's disease, and plexiform xanthomatous tumor), and tumors with myoepithelial differentiation. The section devoted to selected pseudotumoral entities considered representatives of the hamartoma group (neural fibrolipomatous hamartoma, ectopic hamartomatous thymoma, rudimentary meningocele), metabolic diseases (amyloid tumor, nephrogenic fibrosing dermopathy, tophaceous pseudogout, pseudoinfiltrative parathyromatosis), stromal tissue reactions to trauma (fibroosseous pseudotumors of digits) and infections (bacillary angiomatosis), and normal organs (glomus coccygeum). To conclude the descriptive phase, supplementary material has now been collected and appended in an attempt to provide a quick digest of essential knowledge both for comparison and differential diagnosis. The data have been tailored to synthesize diverse sources, integrating clinical elements and references to articles that previously appeared in Part I ("Introduction"), Part II ("The List and Review of New Entities") and Parts III to XI ("Excerpta"). At the very least we hope this final part ("Appendix") will provide the reader with a useful tabular organization of ST lesions and a reference resource.

[Unusual non-neoplastic lesions in the "surgical pathology" of the thyroid]. / Lesioni inusuali non-neoplastiche in "surgical pathology" della tiroide.

This review aims to describe and assist in the categorization of most of the unusual non-neoplastic conditions, encountered in the surgical pathology of the thyroid. The conditions included are: normal intrathyroidal vestigial tissues/structures (i.e. rests of the ultimobranchial body and thyroglossal duct) and their relevant pathological derivatives (ultimobranchial body cyst, intrathyroidal lymphoepithelial cyst, thyroglossal duct cyst); mature intrathyroidal heterologous tissues/organs of either metaplastic or heterotopic origin (adipose tissue, striated skeletal muscle, cartilage, parathyroid glands, thymus, salivary gland tissue) and their relevant pseudotumoural lesions; varieties of metaplastic and non-metaplastic morphologic changes of the thyroid follicular epithelium (oncocytic, clear cell/signet ring cell, darkly pigmented cell, mucinous (myxoid), squamous, spindle cell); amyloid goiter; some reactive and/or degenerative cytologic and nuclear atypicalities (nuclear pseudoclearing and cell pleomorphism) as well as some hyperplastic or peculiar growth patterns (capsular pseudoinvasion; vascular invasion; papillary carcinoma-like and paraganglioma-like patterns) of benign conditions mimicking neoplasia; and finally. some pseudotumoural lesions of the stroma (pseudoangiosarcomatous vascular proliferation, and post-fine-needle aspiration spindle cell nodule). The pathogenetic mechanism, the morphologic interpretation, and the differential diagnosis of each of the above-listed conditions are discussed and pertinent illustrations for many of them are also provided. Lesions of thyroid tissue situated outside of the gland itself are not discussed.

Postchemotherapy residual masses in germ cell tumor patients: our experience.

BACKGROUND: The nature of post-chemotherapy tumor residuals can be determined only by excision and histological examination, but at present no consensus has been reached as to whether all patients with residual masses should undergo adjunctive surgery. PATIENTS AND METHODS: Between August 1991 and September 2004, 120 patients with metastatic germ cell tumors were diagnosed at our hospital and 35 of these patients (30%) underwent adjunctive surgery after cisplatin-based chemotherapy. If serum tumor markers were still raised salvage chemotherapy was administered. RESULTS: At the time of surgical intervention 30 patients (86%) had a partial remission with normal markers. Necrosis, differentiated teratoma and undifferentiated tumor were found in nine (30%), 19 (63%) and two (7%) of all patients. Five patients (14%) underwent postchemotherapy resections after second-line cisplatin-based combination chemotherapy. Four of the 35 patients died as a result of their malignant germ cell tumor. The median observation time after the initial diagnosis was 99 months (range 15-172 months). CONCLUSIONS: Secondary resection of residual masses after first or second-line chemotherapy is still an essential part of the treatment of metastatic testicular cancer. Resection of mature teratoma or viable cancer adds to long-term event-free and overall survival in these patients.

Real-time detection of Helicobacter Pylori infection and atrophic gastritis: comparison between conventional methods and a novel device for gastric juice analysis during endoscopy.

BACKGROUND AND STUDY AIMS: Gastric juice may represent a valuable source of clinicopathological information if properly analyzed. We evaluated the reliability and clinical validity of data obtained using an innovative device (the "Mt 21-42") that analyzes gastric juice, thus allowing the identification of Helicobacter pylori infection and atrophic gastritis of the oxyntic mucosa during endoscopy. METHODS: Validation studies were carried out to evaluate the measuring performance of the device. In addition, the H. pylori status and the presence of atrophic gastritis were assessed in 150 patients undergoing upper gastrointestinal endoscopy. In all these patients the Mt 21-42 device was used to assist endoscopy. Conventional tests (involving histology, urease testing, urea breath testing, anti- H. pylori IgG, serum gastrin, pepsinogen, intrinsic factor and parietal cells autoantibodies, vitamin B12, and folate) were also performed for comparison with the Mt 21-42 results. RESULTS: The measuring performance of the Mt 21-42 was good; for pH, the relative percent error and the coefficient of variation were 1.9 % +/- 4.2 and 1.3 %, respectively, and for ammonium they were 0.1 % +/- 0.2 % and 2.1 %. For the detection of H. pylori infection, the sensitivity and specificity of the device (96.7 % and 94.3 %) were similar to those of the urea breath test (90.5 % and 93.3 %) and serology (87.1 % and 88.8 %), and higher than those of the urease test (78.6 % and 98.7 %; P < 0.01) and routine histology (94.3 % and 76.3 %; P < 0.05). When compared with the currently available standard methods, use of the Mt 21-42 was found to be the most sensitive technique for the detection of atrophy (94.7 % vs. 5.3 % - 47.4 %; P < 0.001); the device failed to detect the disease in only one case (5 %), whereas failure rates of 53 % - 95 % were reported with the conventional methods. CONCLUSION: Atrophic gastritis of the oxyntic mucosa is a risky condition that often goes undetected in current clinical practice. The Mt 21-42 is an effective, useful, and desirable tool that may help to overcome this diagnostic limitation; it produces time and cost savings and also allows the detection of H. pylori infection.