Palatal ancient schwannoma: optical, immunohistochemical and ultrastructural study with literature review.

Schwannoma or neurilemmoma is a benign encapsulated slow-growing tumor that originates from a Schwann cell of a nerve, and is rare at intraoral locations. Different histological variants of schwannomas have been described, of these degenerative or ancient schwannoma is probably one of the least common in the oral cavity with only 16 previously reported cases, of which only one has been described in palatal location. Although ancient schwannoma shows particular characteristics, it is difficult to diagnose based on clinical and imaging appearance alone; as a result, morphological examination assisted by ancillary techniques is necessary to establish a definite diagnosis. We present a clinicopathological description of this rare variant of schwannoma, located in an unusual intraoral site, of a 26-year-old female. We illustrate the optical, immunohistochemical and ultrastructural characterization that aid diagnosis, as well as providing a review of the relevant published data of this unusual tumor.

Immunohistochemical expression of glucose transporter 1 in keratin-producing odontogenic cysts.

BACKGROUND: Keratin-producing odontogenic cysts (KPOCs) are a group of cystic lesions that are often aggressive, with high rates of recurrence and multifocality. KPOCs included orthokeratinised odontogenic cyst (OOC) and parakeratotic odontogenic cysts, which are now considered true tumours denominated keratocystic odontogenic tumours (KCOTs). GLUT1 is a protein transporter that is involved in the active uptake of glucose across cell membranes and that is overexpressed in tumours in close correlation with the proliferation rate and positron emission tomography (PET) imaging results. METHODS: A series of 58 keratin-producing odontogenic cysts was evaluated histologically and immunohistochemically in terms of GLUT1 expression. Different data were correlated using the beta regression model in relation to histological type and immunohistochemical expression of GLUT1, which was quantified using two different morphological methods. RESULTS: KPOC cases comprised 12 OOCs and 46 KCOTs, the latter corresponding to 6 syndromic and 40 sporadic KCOTs. GLUT1 expression was very low in OOC cases compared with KCOT cases, with statistical significant differences when quantification was considered. Different GLUT1 localisation patterns were revealed by immunostaining, with the parabasal cells showing higher reactivity in KCOTs. However, among KCOTs cases, GLUT1 expression was unable to establish differences between syndromic and sporadic cases. CONCLUSIONS: GLUT1 expression differentiated between OOC and KCOT cases, with significantly higher expression in KCOTs, but did not differentiate between syndromic and sporadic KCOT cases. However, given the structural characteristics of KCOTs, we hypothesised that PET imaging methodology is probably not a useful diagnostic tool for KCOTs. Further studies of GLUT1 expression and PET examination in KCOT series are needed to confirm this last hypothesis.

Differential expression of cyclin D1 in keratin-producing odontogenic cysts.

OBJECTIVES: The aim of the present study was to analyze the expression levels of Cyclin D1 (CCD1), a nuclear protein that plays a crucial role in cell cycle progression, in a series of keratin-producing odontogenic cysts. STUDY DESIGN: A total of 58 keratin-producing odontogenic cysts, diagnosed over ten years and classified according to the WHO 2005 criteria, were immunohistochemically analyzed in terms of CCD1 expression, which was quantified in the basal, suprabasal and intermediate/superficial epithelial compartments. The extent of immunostaining was measured as a proportion of total epithelial thickness. Quantified immunohistochemical data were correlated with clinicopathological features and clinical recurrence. RESULTS: Keratin-producing odontogenic cysts were classified as 6 syndromic keratocystic odontogenic tumors (S-KCOT), 40 sporadic or non-syndromic KCOT (NS-KCOT) and 12 orthokeratinized odontogenic cysts (OOC). Immunohistochemically, CCD1 staining was evident predominantly in the parabasal region of all cystic lesions, but among-lesion differences were apparent, showing a clear expansion of parabasal compartment especially in the S-KCOT, followed to a lesser extent in the NS-KCOT, and being much more reduced in the OOC, which had the greatest average epithelial thickness. CONCLUSIONS: The differential expression of CCD1 noted in the present study suggests that dysregulation of cell cycle progression from G1 to the S phase contributes to the different aggressiveness of these lesions. However, CCD1 expression levels did not predict NS-KCOT recurrence, which is likely influenced by factors unrelated to lesion biology.

[Immunophenotypic classification of 3 cases of hepatocellular adenoma. Differential diagnosis with focal nodular hyperplasia]. / Clasificación inmunofenotípica de 3 casos de adenomas hepatocelulares. Diagnóstico diferencial con hiperplasia nodular focal.

Interest in adenomas has been renewed by the discovery of the molecular changes in these tumors. The latest World Health Organization publication on gastrointestinal tract tumors (2010) includes four types of hepatic adenomas, which are well characterized immunohistochemically, genotypically and phenotypically. In these tumors, medical history and morphological behavior play an important role in determining the risk of malignancy, mainly in adenomas with a b-catenin mutation. The presence of steatosis, inflammation, vascular changes linked to response to L-FABP, serum amyloid A, and glutamyl synthetase help to classify these tumors into four groups: hepatocellular adenomas with the HNF1A mutation (H-HCA), those with the b-catenin mutation (b-HCA), inflammatory HCA (IHCA), and HCA without markers. The absence of glypican 3 expression, HSP 70 and perivenular mapping of glutamyl synthetase helps to distinguish these tumors from well differentiated hepatocellular carcinoma. We describe the clinical, morphological and immunophenotypic features of three patients diagnosed with hepatic adenomas in a 2-year period.

Adult rhabdomyoma with oncocytic changes affecting the floor of the mouth: optical, immunohistochemical, and ultrastructural study.

Adult rhabdomyoma (AR) is an extremely uncommon benign neoplasm with mature skeletal muscle differentiation comprising approximately 2% of muscle tumors, usually affecting the soft tissue of the head and neck. Although histology of AR is characteristic, several differential diagnoses (granular cell tumor, hibernoma, oncocytoma) should be considered, and one needs to be familiar with this rare entity to exclude other neoplastic diseases. We present a case of AR, in a 54-year-old man, affecting the floor of the mouth, and call attention to the oncocytic appearance (including antimitochondrial and peroxiredoxin I immunoreactivity) of this case and its differential diagnosis analyzed at the optical, immunohistochemical, and ultrastructural level, showing the morphological and immunohistochemical features that can be confused with a salivary oncocytoma.

Cytological changes in the oral mucosa after use of a mouth rinse with alcohol. A prospective double blind control study.

AIM: The aim of this preliminary study was to detect cytological changes in the oral mucosa after using a mouth wash with alcohol. MATERIAL AND METHODS: A prospective double-blind, controlled study was performed, for 6 months. Group 1 consisted of 30 subjects who used a mouth rinse with 26.9% of alcohol [Listerine] and Group 2 consisted of 30 subjects who used a mouth rinse with the same ingredients but with no alcohol. We obtained three cytological samples from the oral mucosa. The presence of cytological atypia, binucleation and karyorrhesis, and type of cells were studied. We also used a fluorescent in situ hybridization technique (FISH) in 15 samples in each group, for the micronucleus. RESULTS: We found no clinical mucosal alteration after using the mouth wash at the end of the study in either group. We observed no cytological differences between the groups at the end of the study (p>0.05). Regarding the study of the micronucleus by FISH, we observed no significant difference between the groups (p>0.05). CONCLUSIONS: Our results showed no cytological alteration in patients using a mouth rinse with alcohol, but these findings should be considered preliminary results, to be confirmed in a greater sample of patients.

Axonemal Symmetry Break, a New Ultrastructural Diagnostic Tool for Primary Ciliary Dyskinesia?

Diagnosis testing for primary ciliary dyskinesia (PCD) requires a combination of investigations that includes study of ciliary beat pattern by high-speed video-microscopy, genetic testing and assessment of the ciliary ultrastructure by transmission electron microscopy (TEM). Historically, TEM was considered to be the "gold standard" for the diagnosis of PCD. However, with the advances in molecular genetic techniques, an increasing number of PCD variants show normal ultrastructure and cannot be diagnosed by TEM. During ultrastructural assessment of ciliary biopsies of patients with suspicion of PCD, we observed an axonemal defect not previously described that affects peripheral doublets tilting. To further characterize this defect of unknown significance, we studied the ciliary axonemes by TEM from both PCD-confirmed patients and patients with other sino-pulmonary diseases. We detected peripheral doublets tilting in all the PCD patients, without any significant difference in the distribution of ciliary beat pattern or mutated gene. This defect was also present in those patients with normal ultrastructure PCD subtypes. We believe that the performance of axonemal asymmetry analysis would be helpful to enhance diagnosis of PCD.

Perioperative ischemic injury and fibrotic degeneration of muscle in a forearm allograft: functional follow-up at 32 months post transplantation.

Allografts of the forearm are still uncommon in the field of composite tissue allograft transplantation. In November 2007, a right-hand allograft and a left-hand/full-length forearm allograft were transplanted in a 30-year-old man who lost both hands and the vision in his left eye due to an explosion. The patient underwent alemtuzumab and steroid induction therapy. Tacrolimus, mycophenolate mofetil, and low doses of steroids were given to prevent rejection. The allografts were rejected 3 times, but these episodes were controlled successfully. The immunosuppressive regimen was switched from tacrolimus to sirolimus because of increased serum creatinine. The left allograft showed a flexion contracture due to muscle fibrosis that was conjectured to be associated with a perioperative ischemic injury and permitted only a Moberg-type key pinch. In contrast, an excellent grade of function was observed in the right allograft. The Disabilities of the Shoulder, Arm, and Hand score improved from 70.83 to 36.6 and intrinsic musculature returned to both allografts. The patient was able to work 2 years after transplantation. This is the first report of an ischemic injury related to the successful allotransplantation of a composite tissue.

Value of KI-67/MIB-1 labeling index and simpson grading system to predict the recurrence of who grade I intracranial meningiomas compared to who grade II.

Simpson grading of resection has been used as a predictor of intracranial meningioma (IM) recurrence. Histopathological findings, like the Ki-67/MIB-1 labeling index, may be useful in the assessment risk of recurrence. Our objective was to analyze the predictive value of meningioma recurrence using both parameters. We retrospectively studied 322 consecutive patients with histopathological diagnosis of IM WHO grade I and 43 patients with IM WHO grade II in a 13-year period. Multivariate survival analysis was performed. In the WHO grade I IM group, recurrence was observed in 28 patients (8.69%). The Cox regression model for WHO grade I IM, provided a significative hazard ratio (HR) for Ki-67/MIB-1 index ≥3 (HR = 36.35, p < 0.001) and Simpson's grading resection, grade II (HR = 2.03, p = 0.045), grade III (HR = 3.41, p = 0.034) and grade IV (HR = 19.75, p ≥ 0.001). In the WHO grade II IM group, recurrence was observed in 10 patients (23.25%). The Cox regression model for WHO grade II IM, provided a significative hazard ratio (HR) for Ki-67/MIB-1 index ≥3% (HR = 1.66, p < 0.001) and Simpson's grading resection grade III (HR = 3.96, p = 0.027). The Kaplan-Meier survival curve showed a similar distribution of survival between WHO grade I IM with Ki-67/MIB-1 ≥3% and WHO grade II IM. In WHO grade I meningiomas, the Ki-67/MIB-1 index and Simpson grading were both independent predictors of recurrence. A similar management protocol should be advisable for WHO grade I with Ki-67/MIB-1 ≥3% and WHO grade II meningiomas.

Intratumoral immunosuppression profiles in 11q-deleted neuroblastomas provide new potential therapeutic targets.

High-risk neuroblastoma (NB) patients with 11q deletion frequently undergo late but consecutive relapse cycles with fatal outcome. To date, no actionable targets to improve current multimodal treatment have been identified. We analyzed immune microenvironment and genetic profiles of high-risk NB correlating with 11q immune status. We show in two independent cohorts that 11q-deleted NB exhibits various immune inhibitory mechanisms, including increased CD4+ resting T cells and M2 macrophages, higher expression of programmed death-ligand 1, interleukin-10, transforming growth factor-beta-1, and indoleamine 2,3-dioxygenase 1 (P < 0.05), and also higher chromosomal breakages (P ≤ 0.02) and hemizygosity of immunosuppressive miRNAs than MYCN-amplified and other 11q-nondeleted high-risk NB. We also analyzed benefits of maintenance treatment in 83 high-risk stage M NB patients focusing on 11q status, either with standard anti-GD2 immunotherapy (n = 50) or previous retinoic acid-based therapy alone (n = 33). Immunotherapy associated with higher EFS (50 vs. 30, P = 0.028) and OS (72 vs. 52, P = 0.047) at 3 years in the overall population. Despite benefits from standard anti-GD2 immunotherapy in high-risk NB patients, those with 11q deletion still face poor outcome. This NB subgroup displays intratumoral immune suppression profiles, revealing a potential therapeutic strategy with combination immunotherapy to circumvent this immune checkpoint blockade.

Intraosseus plexiform schwannoma of the mandible: immunohistochemical differential diagnosis.

Schwannomas and neurofibromas are the most common benign tumors derived from peripheral nerves, and whereas the head and neck region is the most common location for the occurrence of benign neural sheath neoplasms, origin within the oral cavity is uncommon, and occurrence centrally in the jaws is most unusual. Plexiform (multinodular) schwannoma is an anatomically unique variant of schwannoma characterized grossly and/or microscopically by intraneural plexiform and often multinodular growth. In current report, we present the first reported case of intraosseous plexiform schwannoma of the mandible, an extremely rare benign neurogenic tumor, diagnosed by optical and immunohistochemical procedures, showing the importance of differential diagnosis of these unusual intraosseous mandibular tumors.

The Frequency and Prognostic Significance of the Histologic Type in Early-stage Ovarian Carcinoma: A Reclassification Study by the Spanish Group for Ovarian Cancer Research (GEICO).

The frequency and prognostic significance of the histologic type in early-stage ovarian cancer (OC) is not as well established as in advanced stages. In addition, histologic typing based only on morphologic features may be difficult, especially in high-grade tumors. In this study, we have analyzed a prospective cohort of 502 early-stage OCs to investigate their frequency, immunohistochemical characteristics, and survival of the 5 main histologic types. Histotype was assigned according to not only the morphologic features but also according to the expression pattern of WT1, p53, Napsin A, and progesterone receptors. In addition, an extended panel including p16, ß-catenin, HER2, Arid1A, HINF1B, CK7, CDX2, and CK20 was used to refine the diagnosis in difficult cases. In this series, the frequency of the 5 major histologic types was as follows: endometrioid carcinoma, 32.7%; clear cell carcinoma, 25.1%; high-grade serous carcinoma (HGSC), 24.7%; mucinous carcinoma, 10.2%; low-grade serous carcinoma, 4.6%; and others, 2.8%. The combination of morphology and immunohistochemistry allowed the reclassification of 23% of OCs. The lowest concordance was found between samples initially diagnosed as endometrioid, but finally classified as high-grade serous tumors (22% error rate). Endometrioid carcinoma was the most favorable histologic type, whereas HGSC and low-grade serous carcinoma had the worst prognosis. Clear cell carcinoma with abnormal p53 immunostaining pattern also had poor prognosis. Although histologic grade was not a prognostic factor among early-stage endometrioid OCs, distinction between grade 3 endometrioid OC and HGSC is recommended, taking into account differences in prognosis and molecular alterations that can guide different treatments.

[Gastric gastrointestinal stromal tumour and schwannoma: An unusual presentation in a patient without neurofibromatosis]. / Tumor del estroma gastrointestinal y schwannoma gástricos: una presentación inusual en un paciente sin neurofibromatosis.

The majority of gastric neoplasms are of epithelial type. Stromal tumours are the next most frequent and are most commonly gastrointestinal stromal tumours, followed by leiomyoma and schwannoma. We present an exceptional case of a patient with a gastrointestinal stromal tumour with suspicion of residual gastric disease, which was diagnosed post-operatively as a schwannoma.

[Tubulocystic renal cell carcinoma. A rare entity in neoplastic renal pathology]. / Carcinoma tubuloquístico. Una entidad infrecuente en la patología tumoral renal.

Tubulocystic renal carcinoma is an uncommon neoplasm. We present a case of a patient presenting with multiple renal colic. A nodular cystic lesion was an incidental sonographic finding which increased in size during subsequent follow-ups. The patient underwent radical nephrectomy and tubular renal carcinoma was diagnosed histopathologically and immunohistochemically.

Orthokeratinized odontogenic cysts: a Spanish tertiary care centre study based on HPV DNA detection.

BACKGROUND: The role of human papillomavirus (HPV) in orthokeratinized odontogenic cysts (OOCs) has rarely been studied. The objective is to describe the clinicopathological findings in a series of OOCs from a Spanish population that were investigated in relation to the possible presence of HPV. METHODS: A clinicopathological retrospective analysis followed by a molecular analysis of 28 high- and low-risk HPV genotypes was performed in OOC samples of patients seen during the last 15-years in a Spanish tertiary care center. RESULTS: Of 115 odontogenic cysts with keratinization, 16 cases of OOCs were confirmed and evaluated. OOCs occurred predominantly in the mandible of males (mean age 36.06 ± 13.16 years). Swelling of the jaw followed by pain were the most common clinical symptoms, and 56.5% of the OOC cases were associated with an unerupted tooth. After a mean post-cystectomy follow-up of 3.8 years, only one recurrent case was observed, resulting in a verrucous cystic lesion that was considered premalignant after immunohistological examination. DNA extraction was successful from 14 of the 16 OOC cases. None of the primary OCCs or the single recurrent OOC were positive for HPV in the molecular analysis. CONCLUSIONS: OOCs show a very limited potential for recurrence. Our results suggest that neither high- or low-risk HPV subtypes are likely to play a role in the etiology or neoplastic transformation of OOC, at least in the Spanish population.

In memoriam: Las aportaciones micrográficas del valenciano Luis Simarro (1851-1921) / In memoriam: The histological contributions of Dr. Luis Simarro (1851-1921)

El pasado 19 de junio del 2021, se cumplió el centenario de la muerte del histólogo valenciano Luis Simarro Lacabra (1851-1921). La figura de Simarro prácticamente ha desaparecido, en el momento actual, de la memoria del panorama científico y cultural español, siendo sus aportaciones micrográficas escasamente conocidas, probablemente debido a que su producción científica escrita fue muy reducida. En el presente trabajo, las aportaciones micrográficas de Simarro, de las que tenemos conocimiento, son revisadas en el contexto de su biografía, analizando su influencia en el origen y desarrollo de la escuela neurohistológica española que, liderada por Santiago Ramón y Cajal, es hoy universalmente reconocida.(AU)

The centenary of the death of the Valencian histologist Luis Simarro Lacabra (1851-1921) was celebrated on the 19th of June 2021. However, today little of his work is remembered and his valuable contribution to histology is scarcely known. This is probably due to his limited publications. We review Simarro's histological research in the context of his biography and analyse how it influenced Santiago Ramón y Cajal and the development of neurohistology.(AU)

Follicular adenomatoid odontogenic tumor: immunohistochemical study.

Adenomatoid odontogenic tumor (AOT) is an uncommon benign odontogenic lesion that affects young patients, with female predominance, mainly in second decade, showing a radiolucent unilocular image associated with an unerupted tooth, usually a canine. In spite of previous and confusing denominations, such as adenoameloblastoma or adenomatoid ameloblastic tumor, AOT is a benign tumor with a very low rate of recurrence, that show a peculiar morphological picture (basaloid appearance with glandular-like structures, calcifying areas, and amiloid-like material) that allow its histopathological recognition. We present a clinicopathological analysis of a case of follicular AOT affecting the mandible in a 9 years-old female patient associated with unerupted lower left canine. Immunohistochemical study showed some data previously unrecognised. All cellular types that composed AOT showed nuclear positivity for p63 indicating a basal characterization in the different cellular components. According to its benign character and low potential for recurrence, AOT revealed a scant proliferative activity (2-3% nuclei showed Ki-67 positivity) limited to some epithelial nodules (AE1-3 +) of fusiform appearance. Absence of reactivity for hormonal receptors (RE and RPg) excluded a possible hormonodependence in AOT that could explain the observed female predominance.

[Perioperative mortality of lung transplantation in chronic obstructive pulmonary disease]. / Mortalidad perioperatoria del trasplante pulmonar en la enfermedad pulmonar obstructiva crónica.

INTRODUCTION: Lung transplantation (LT) has been considered an alternative therapeutic approach in terminal patients. However, this process in COPD is not controversy-free. This paper aimed to analyze 30-day mortality (PM) patterns and their risk factors in COPD patients undergoing LT. PATIENTS AND METHOD: A retrospective cohort with 107 COPD patients, transplanted at the University La Fe Valencia, Spain, treated from January 1991 to December 2008. Demographics values, degree of dyspnoea, diagnosis, BODE index, single versus bilateral LT, cardio-pulmonary bypass, donor age, steroid dependence, presence of bronchiectasis, retrograde perfusion, transfusion of blood products, and PaO2/FiO2 were analyzed. Continuous variables were expressed as mean±SD and categorical variables as absolute frequency and percentage. A Cox regression model was used for multivariate analysis. RESULTS: Ninety-four men and 13 women of a mean age of 52.58±8.05 years were transplanted. Of all patients, 75% obtained a BODE score above 7. There were 76 bilateral LT. PM was established at 14%. Main causes of death were infection (53.3%) and surgical complications (33.3%). Presence of bronchiectasis and chronic use of corticosteroids, donor/recipient difference in size and presence of fat in retrograde perfusion fluid were important risk factors for PM. Moreover, PaO2/FiO2 ratio at 6h was a protective factor for the event, thus a higher ratio value, lowered the risk of PM. CONCLUSIONS: LT is a procedure with a high PM rate. Use of corticosteroids, the presence of bronchiectasis and fat emboli in the retrograde reperfusion, and PaO2/FiO2 significantly determine PM.

Cytological characteristics of acinic cell carcinoma (ACC) diagnosed by fine-needle aspiration biopsy (FNAB). A study of four cases.

OBJECTIVE: To present the cytopathological characteristics of acinic cell carcinoma (ACC) as well as its cyto-histological correlation, commenting on the differential diagnostic problems of this entity based on four observations studied using fine-needle aspiration biopsy (FNAB). CLINICAL CASES: Two males of 52 and 53 years of age, one 79 year-old woman and a girl of 12 years of age, who presented tumors located in the parotid area (cases 1, 2 and 4) and at the laterocervical level (case 3). In 3 patients, the FNAB was, together with the image studies, the first diagnostic indication; case 3 corresponding to a puncture of metastatic laterocervical adenopathies in a patient with a history of parotid ACC. CYTOLOGICAL FINDINGS: The cytologic smears revealed abundant tumoral cellularity arranged in small monolayered sheets, forming acinar structures or isolated cells. The abundance of bare nuclei at the background of the smears, and the absence of adipose tissue and ductal epithelium are highlighted. The cells possessed round or oval monomorphic nuclei, few nucleoli and abundant granular or finely vacuolate cytoplasm. DISCUSSION: FNAB provides essential information on the diagnostic-therapeutic management of salivary gland tumors; this methodology is highly sensitive in its diagnostic efficacy. The diagnosis of ACCs frequently presents difficulties, owing to the great cytologic similarity of the tumor cells with the normal acinar component of the salivary gland. The differential diagnosis is considered, fundamentally, with clear cell carcinomas, mucoepidermoid carcinomas, Warthin s tumor, and oncocytomas. Our observations confirm the validity of FNAB in a first diagnostic approximation for those lesions accessible to direct puncture.