Specific Histologic Criteria Research Articles

Metastatic Granular Cell Tumor: A Rare Entity.

Granular cell tumor, which is thought to recapitulate a Schwann cell phenotype, is a very rare neoplasm that belongs to soft tissue tumors. It can be classified as benign, atypical or malignant, based on specific histological criteria, with the majority of cases exhibiting an indolent behavior. Its biology and clinical course are poorly understood and its optimal management is yet to be defined, given the rarity of cases. Here we describe an atypical granular cell tumor in the upper middle back skin that evolved after a thirty-year indolent period. Despite complete surgical removal, the patient experienced a recurrence, both local and in the lungs, following an aggressive clinical course. Data on management of metastatic disease are extremely scarce, comprised exclusively of case reports. Therefore, we administered to the patient systemic therapy according to soft tissue sarcoma guidelines, which led to disease progression, with fatal outcome. In conclusion, recurrent and/or metastatic granular cell tumor is a rare disease that can be life-threatening, for which response to different therapies is unknown. The biologic behavior of atypical and malignant granular cell tumor is quite different from its benign counterpart, evoking soft tissue sarcomas, and its diagnosis should alert clinicians. The role of adjuvant chemotherapy and radiation therapy in this setting should be explored, to limit disease recurrence.

37. Pleomorphic Dermal Sarcoma (PDS) – who should be getting it right first time?

The introduction of specific histological criteria for diagnosing PDS has resulted in MDT’s seeing more of these cases. We had noted anecdotal reports of widespread variation in pathways and a lack of clear guidance on PDS management.

Not all low grade dysplasia in Barrett's oesophagus is the same: using specific histological criteria in predicting progression to neoplasia.

Barrett's oesophagus with low grade dysplasia (LGD) is a risk factor for progression to high grade dysplasia (HGD) and oesophageal adenocarcinoma (OAC); however, only a subgroup of LGD will progress. We used a combination of specific histological criteria to identify patients with LGD who are more likely to progress to HGD or OAC. LGD slides from 38 patients within the progressor group (PG) and 17 patients from the non-progressor group (NPG) were obtained and reviewed by two expert GI pathologists, to be stratified by the same four specific histological variables identified by Ten Kate etal.: loss of surface maturation, mucin depletion, nuclear enlargement, and increase of mitosis. After review of LGD slides by two expert GI pathologists, 27 suitable patients were identified. Of these 27 patients there was a higher proportion of patients from the PG with all four specific criteria reported, compared to the NPG: 14 (78%) vs 3 (33%) p=0.0394. Patients with all four specific criteria were more likely to progress compared to those who had one or less specific criteria reported (OR 7, 95% CI 1.1848-41.3585, p=0.032). A combination of ≥2 or ≥3 specific histological criteria was not prognostic. Patients with a combination of all four specific histological criteria (loss of surface maturation, mucin depletion, nuclear enlargement, and increase of mitosis) were associated with greater progression from LGD to HGD or OAC in Barrett's oesophagus.

Knowledge and practice regarding prostate cancer germline testing among urologists: Gaps to address for optimal implementation✰,✰✰

BackgroundGermline testing is recommended for all men with metastatic prostate cancer (PCa), and for some with localized PCa meeting specific histologic or family history criteria. Germline genetic evaluation has important implications for PCa prognosis and management, as well as implications for family members and cancer screening. Despite the importance of germline evaluation, its utilization in urologic practice is unknown. Materials and MethodsWe conducted a 32-item survey of U.S. urologists to examine knowledge of germline testing guidelines and practice patterns. It was shared through email to 6 American Urological Association sections, the Veterans Affairs Urology Mailgroup, and social media. ResultsAmong 132 total respondents from diverse practice settings across the U.S., 12% perform germline testing, 44% refer to a genetic counselor, 11% do both, and 33% do not test/refer. Only 4% had formal education in genetics. While 98% ask about PCa family history, only 76% and 52% ask about breast and ovarian cancer. When presented with hypothetical case scenarios where germline testing is indicated, many respondents indicated they would not offer genetic counseling or testing. Younger age (p = 0,03), academic practice (p = 0.04), and specializing in PCa/oncology (p = 0.007) were significantly associated with performing or referring for germline testing. Specializing in PCa/oncology was significantly associated with recommending germline testing for all case scenarios involving metastatic PCa (p = 0.0009) ConclusionOur results suggest significant gaps in knowledge of germline testing and alignment of practice with national guidelines among urologists. Germline testing education and facilitation of genetic evaluation in urologic practice is warranted.

Glomus tumor of uncertain malignant potential in the arm of an elderly female – Report of an unusual case

Malignant glomus tumors (GTs) are very rare, and diagnosis requires consideration of specific histologic criteria based on a combination of criteria such as size of the tumor, degree of nuclear atypia, and the level of mitotic activity. GTs that do not fulfill the histologic criteria for malignancy but show at least one feature other than nuclear atypia should be classified as GT of uncertain malignant potential (GTUMP). We report the case of a 65-year-old female with a slowly progressing soft-tissue swelling in the right lower arm near the elbow joint that was successfully treated through wide surgical excision and histologically diagnosed as a GTUMP. On follow-up after 3 months, there was no evidence of recurrence or metastasis. Malignant GTs and GTUMPs are rare, and the nomenclature and classification of these tumors is controversial. These findings and the difficulty of differential diagnosis in a continuum between benignity and malignancy prompted our report.

STANDARDIZATION OF THE HISTOLOGIC DIAGNOSIS OF ASPIRATION

SESSION TITLE: Tuesday Abstract Posters SESSION TYPE: Original Investigation Posters PRESENTED ON: 10/22/2019 01:00 PM - 02:00 PM PURPOSE: Pulmonary aspiration is the diversion of food or liquid into the trachea and potentially the lower respiratory tract. An acute response to aspiration may include pneumonia or alveolitis; chronic aspiration response includes diffuse alveolar damage and has been implicated in the pathogenesis of idiopathic pulmonary fibrosis. (Raghu Eur Respir J. 2006; 27:136–42) Diagnosis of aspiration is difficult and low sensitivity (50%) has been documented for screening tests (Zhou Eur J Phys Rehab Med 2011; 47:441-6). Ultimately, lung tissue examination confirms pulmonary aspiration; however, a lack of standardization of the histologic definition of aspiration exists. We separated the specimens into categories of confirmed aspiration, possible aspiration and unconfirmed aspiration and define the criterion for each category. METHODS: A retrospective electronic query was performed on all 798 lung specimens obtained between January 1, 2015 to December 31, 2018 to identify lung histology with an interpretation of aspiration. A total of 24 specimens were identified (18 lung transplant recipients and 6 non-transplant recipients) and reviewed by two pulmonary pathologists. Specimens were subsequently separated into categories of confirmed aspiration based on the presence of vegetable matter or skeletal muscle in the lung parenchyma, possible aspiration if multinucleated giant cells with intracytoplasmic lipids were present and unconfirmed aspiration if these specific criteria were not present. RESULTS: Confirmed aspiration was defined in 8/24 (33%) specimens, possible aspiration was present in 5/24 (21%), and unconfirmed aspiration was identified in 11/24 (46%) specimens. All (8/8, 100%) of the confirmed aspiration and possible aspiration (5/5; 100%) specimens were obtained from lung transplant recipients. Of the 11 unconfirmed aspiration specimens, 5 were obtained from transplant recipients and 6 obtained from non-transplant recipients. CONCLUSIONS: Confirmed aspiration was present in 8/24 (33%) specimens, possible aspiration was present in 5/24 (21%), and unconfirmed aspiration was identified in 11/24 (46%) specimens. All (8/8, 100%) of the confirmed aspiration and possible aspiration (5/5; 100%) specimens were obtained from lung transplant recipients. Of the 11 unconfirmed aspiration specimens, 5 were obtained from transplant recipients and 6 obtained from non-transplant recipients. CLINICAL IMPLICATIONS: Aspiration has been linked with acute and chronic lung disease; however diagnostic histologic criteria have not been established. The absence of specific histologic criteria may prevent the identification of a cohort of patients with confirmed aspiration. As a result, elucidation of the pathophysiology of this disorder may be confounded. Establishing specific diagnostic criteria may identify a more precise cohort of patients for pathophysiologic evaluation. DISCLOSURES: No relevant relationships by Hermona Abera, source=Web Response No relevant relationships by Vijayalakshmi Ananthanarayanan, source=Web Response No relevant relationships by Josefina Corral, source=Web Response No relevant relationships by James Gagermeier, source=Web Response No relevant relationships by Rizwan Mahmood, source=Web Response No relevant relationships by Swati Mehrotra, source=Web Response No relevant relationships by Mukund Venu, source=Web Response No relevant relationships by Krishnan Warrior, source=Web Response

Multinucleate cell angiohistiocytoma: A clinicopathologic study of 62 cases and proposed diagnostic criteria.

Multinucleate cell angiohistiocytoma (MCAH) is an uncommon and likely underdiagnosed entity that is thought to be of vascular and fibrohistiocytic origin. We retrospectively reviewed all cases diagnosed as MCAH at the Yale Medicine Dermatopathology laboratory between 1 January 1990 and 1 September 2018. Sixty-two cases were retained. We performed immunohistochemistry on the ten most inflamed lesions found and assessed for a possible alteration within the Wnt/ß-catenin signaling pathway, involved in follicular induction in dermatofibroma. We subsequently established histologic diagnostic criteria to differentiate MCAH from its mimickers. MCAH affected both genders equally. The hands or fingers were affected in 51.6% of cases. We found the most specific histologic criteria to be: (a) presence of odd multinucleated fibroblasts, (b) presence of superficial parallel fibrosis, (c) presence and thickening of superficial papillary dermal vessels, and (d) absence of perifollicular fibrosis. As for immunoreactivity, we found positivity to CD138, CD163, and CD117 in the mononuclear inflammatory infiltrate. There was no histopathologic evidence of follicular induction, as can be seen in dermatofibromas, and no expression of nuclear beta-catenin as seen in dermatofibromas with follicular induction. This large case series establishes MCAH as a distinct clinical and histopathologic entity.

Evaluation of eight melanocytic and neural crest-associated markers in a well-characterised series of 124 malignant peripheral nerve sheath tumours (MPNST): useful to distinguish MPNST from melanoma?

The diagnosis of malignant peripheral nerve sheath tumour (MPNST) may be challenging, especially in the sporadic setting. Owing to the lack of specific histological criteria, immunohistochemical and molecular diagnostic markers, several differential diagnoses must be considered, especially melanoma. Indeed, although S100 protein usually stains melanoma, other melanocytic markers are often negative, especially in spindle cell/desmoplastic types. This pattern of immunoreactivity resembles that of some nerve-derived tumours such as MPNST. Owing to their different clinical behaviours and therapeutic implications, accurate identification of these two different tumours is crucial. S100, SOX10, KBA62, MITF, HMB45, Melan-A, tyrosinase PNL2 and BRAF-V600E immunostaining was performed in a pathologically and genetically well-characterised cohort of primary MPNST (n=124), including 66 (53%) NF1-associated tumours. Sox10 and KBA62 expression were found, respectively, in 102 (84%) and in 101 (83%) MPNST, whereas S100 was expressed in 64 cases (52%). We observed an increased loss of S100 with increasing histological grade (P=0.0052). We found Melan-A expression in 14% (n=17) of all MPNST, occurring in 82% (n=14) of cases in an NF1 context. Six per cent (n=8) of MPNST showed tyrosinase positivity, including seven (87%) NF1-associated. MITF expression was found in 10 (8%) MPNST. None expressed PNL2, HMB45 or BRAF-V600E. MPNST (in NF1 and a sporadic setting) can quite often be positive for Melan-A, tyrosinase and MITF. Pathologists should be cognisant of these exceptions to prevent confusion with melanoma.

An autopsy case of small vessel, childhood, primary angiitis of the central nervous system (SVcPACNS): suggestions for establishing specific histologic criteria for diagnosis

SVcPACNS is a rare inflammatory/immune disorder that typically affects the small blood vessels of the brain. SVcPACNS differs from most adult forms of PACNS by being predominantly lymphocytic, non-granulomatous and non-necrotizing. Previously healthy children are typically affected by range of signs and symptoms, including: seizures, headache, cognitive decline, behavior/personality change, focal neurological deficits and potentially a decreased level of consciousness. Treatment protocols featuring induction (steroids and cyclophosphamide) and subsequent maintenance phases (e.g., mycophenolate mofetil) have been demonstrated to yield favorable outcomes. Since SVcPACNS is characteristically angiography negative, the diagnostic gold standard is brain biopsy. Interpretation of these biopsies is often challenging given the histologic overlap between SVcPACNS and encephalitis. Distinguishing the foregoing is critical since the treatment of these entities is significantly different.Herein, a rare autopsy case of SVcPACNS in a 4 year old male is presented. This case provides a unique opportunity to review the Alrawi criteria for the histologic diagnosis of PACNS and establish/refine criteria specific to SVcPACNS. Generally, such criteria should feature: 1) an intramural and lymphocyte predominant infiltrate devoid of multinucleated giant cells; 2) structural vessel alterations lacking fibrinoid necrosis; 3) perivascular pathology supportive of an angiocentric process; 4) the absence of encephalitis; and, 5) the absence of a concurrent systemic or rheumatic illness that could account for the CNS findings.

LANAP, Periodontics and Beyond: A Review.

Laser has emerged as an adjunct in several treatment modalities in dentistry in the past few decades. This less invasive bladeless technique is bringing revolutionary outcomes in a plethora of periodontal treatment procedures as well. A unique ameliorative approach termed LANAP, described as laser-assisted new attachment procedure was developed by Gregg and McCarthy. In 1990 they introduced an innovative treatment for diseases of gums incorporating pulsed neodymium yttrium aluminum garnet (Nd: YAG) 1064 nm wavelength laser (PerioLase MVP7). The LANAP concept was endorsed by Yukna et al who conducted a study according to the protocol reinforced at the1996 world workshop in periodontics, which established specific histologic criteria to prove regeneration. Yukna's histological study found that regeneration of the periodontally compromised root could be achieved by Nd: YAG laser. LANAP facilitates refurbishing of new tissues from supporting structures of the periodontium wherein the unhealthy surface of the roots exhibit pristine attachments in human beings. This paper is a review providing a detailed report of LANAP from its inception to recent advances.

Improved Progression Prediction in Barrett's Esophagus With Low-grade Dysplasia Using Specific Histologic Criteria.

Risk stratification of patients with Barrett's esophagus (BE) is based on diagnosis of low-grade dysplasia (LGD). LGD has a poor interobserver agreement and a limited value for prediction of progression to high-grade dysplasia or esophageal adenocarcinoma. Specific reproducible histologic criteria may improve the predictive value of LGD. Four gastrointestinal pathologists examined 12 histologic criteria associated with LGD in 84 BE patients with LGD (15 progressors and 69 nonprogressors). The criteria with at least a moderate (kappa, 0.4 to 0.6) interobserver agreement were validated in an independent cohort of 98 BE patients with LGD (30 progressors and 68 nonprogressors). Hazard ratios (HR) were calculated by Cox proportional hazard regression analysis using time-dependent covariates correcting for multiple endoscopies during follow-up. Agreement was moderate or good for 4 criteria, that is, loss of maturation, mucin depletion, nuclear enlargement, and increase of mitosis. Combination of the criteria differentiated high-risk and low-risk group amongst patients with LGD diagnosis (P<0.001). When ≥2 criteria were present, a significantly higher progression rate to high-grade dysplasia or esophageal adenocarcinoma was observed (discovery set: HR, 5.47; 95% confidence interval [CI], 1.81-17; P=0.002; validation set: HR, 3.52; 95% CI, 1.56-7.97; P=0.003). Implementation of p53 immunohistochemistry and histologic criteria optimized the prediction of progression (area under the curve, 0.768; 95% CI, 0.656-0.881). We identified and validated a clinically applicable panel of 4 histologic criteria, segregating BE patients with LGD diagnosis into defined prognostic groups. This histologic panel can be used to improve clinical decision making, although additional studies are warranted.

Loss of H3K27 trimethylation is not suitable for distinguishing malignant peripheral nerve sheath tumor from melanoma: a study of 387 cases including mimicking lesions

The diagnosis of malignant peripheral nerve sheath tumor remains challenging, especially in the sporadic setting. Malignant peripheral nerve sheath tumor is a rare malignancy, and owing to the lack of specific histological criteria, immunohistochemical and molecular diagnostic markers, several differential diagnoses must be considered, in particular melanoma. Recently, inactivation of the polycomb repressive complex 2 (PRC2), induced by inactivating mutations in two of its critical constituents SUZ12 and EED, was reported in a large subset of malignant peripheral nerve sheath tumors. Homozygous PRC2 inactivation induces complete loss of trimethylation at lysine 27 of histone 3 (H3K27me3). Recent studies suggest that complete loss of H3K27me3 is highly specific for malignant peripheral nerve sheath tumor and may be a useful immunohistochemical diagnostic marker. Therefore, to determine the specificity of the complete loss of H3K27me3 expression in the context of the differential diagnosis of malignant peripheral nerve sheath tumor from melanoma (its major potential mimic), we performed H3K27me3 immunohistochemistry in a pathologically and genetically well-characterized cohort of primary (neurofibromatosis type 1 (NF1), radiation-associated and sporadic context) malignant peripheral nerve sheath tumors (n=122) and in a cohort or primary (desmoplastic) and metastatic melanomas (n=265). In total, 88 (72%) malignant peripheral nerve sheath tumors, including 46 (71%) NF1-associated, 4 (100%) radiation-associated, and 38 (72%) sporadic tumors, showed complete loss of H3K27me3. We observed increased loss of H3K27me3 with increasing histological grade. Interestingly, we found complete loss of H3K27me3 in 37% (n=98) of all melanomas, including 25% (n=9) of primary desmoplastic melanomas. Moreover, partial loss ('mosaic' pattern) was observed in 23 (19%) of all malignant peripheral nerve sheath tumors and in 136 (51%) of all melanomas. Complete loss of H3K27me3 detected by immunohistochemistry is not specific for malignant peripheral nerve sheath tumor and cannot be used safely when distinguishing malignant peripheral nerve sheath tumor from melanoma.

Malignant Peripheral Nerve Sheath Tumor Is a Challenging Diagnosis: A Systematic Pathology Review, Immunohistochemistry, and Molecular Analysis in 160 Patients From the French Sarcoma Group Database.

An accurate histopathologic diagnosis is essential for an adequate treatment of soft tissue sarcomas. The diagnosis of malignant peripheral nerve sheath tumor (MPNST) can be complex, particularly outside the neurofibromatosis type 1 (NF1) context. MPNST is a rare malignancy, and due to the lack of specific histologic criteria, several differential diagnoses must be considered. A total of 350 patients diagnosed with MPNST (from 1990 to 2013) were retrieved from the French sarcoma network (RRePS) and the Conticabase (Connective Tissue Cancer Network database). Tumor samples were available for 160 cases (45.2%). Pathology review, immunohistochemistry (IHC), and molecular analysis (when dealing with a monomorphic sarcoma) were systematically performed. Patient, tumor, and treatment characteristics were evaluated to identify prognostic factors for the definitive primary MPNST (n=106) cohort. Twenty-nine tumors (18.1%) initially diagnosed as MPNST were reclassified on the basis of histologic review, IHC, and molecular analysis. Patients with NF1 disease comprised 64% of the remaining cohort. The 5-year overall survival for patients from the entire cohort was 47%, 34.8% for NF1 patients, and 68.5% for patients without NF1 disease, making NF1 syndrome an independent poor prognostic factor of survival. Positive margins and lack of radiation therapy were independent predictors of local recurrence. The Fédération Nationale des Centres de Lutte Contre le Cancer tumor grade was an independent prognostic indicator of metastasis. Given the therapeutic implications of a misdiagnosis, the systematic pathology review, IHC, and molecular analysis (when dealing with monomorphic sarcoma) strategy allowed reclassification of 20% of cases, mainly the sporadic MPNSTs.

Sa1250 Improved Prediction of Neoplastic Progression in Patients With Barrett's Oesophagus Using Specific Histological Criteria for Low Grade Dysplasia

Sa1250 Improved Prediction of Neoplastic Progression in Patients With Barrett's Oesophagus Using Specific Histological Criteria for Low Grade Dysplasia

The types, incidence and demographic distribution of benign oral and maxillofacial neoplasms among patients attending Muhimbili National Hospital in Tanzania, 2008-2013

Background: Pathological processes of oral and maxillofacial region are generally classified as benign or malignant based on specific histological criteria, including the presence or absence of necrosis, mitotic figures as well as basic understanding of the entity. The objective of this study was to determine the types, prevalence and demographic distribution of benign oral and maxillofacial tumours among patients treated at Muhimbili National Hospital in Tanzania.Methods: In this retrospective study, data on histological results of lesions of the oral and maxillofacial region were retrieved from the archives at the Department of Oral and Maxillofacial Surgery of Muhimbili National Hospital were analysed. The tumour type, age, sex, file number and histopathological diagnosis of the patient were recorded. The study covered a period of from January 2008 to December 2013. The top ten lesions with higher frequency of occurrence from January to were picked for analysis.Results: A total of 897 (males=388; females=509) histological results of patients with benign oral and maxillofacial lesions were obtained during the period under review. The age ranged from 0 to 88 years, mean age being 32.63 ± 17.1 while the age group of 20-29 and 30-39 were the most affected. A total of 136 different types of benign lesions were reported and ameloblastoma was the most common benign lesion (27.4%) followed by ossifying fibroma (18.7%), pyogenic granuloma (11.4%), pleomorphic adenoma (10.0%), and fibrous dysplasia (9.6%). Females were more affected than males, with a male to female ratio of 1:1.4 however the difference was statistically insignificant (p= 0.055).Conclusion: Ameloblastoma and ossifying fibroma were the most common oral and maxillo-facia neoplasms at Muhimbili National Hospital. The young age groups were the most affected by these lesions.

Histologic Findings Predictive of a Diagnosis of De novo Autoimmune Hepatitis After Liver Transplantation in Adults

Autoimmune hepatitis (AIH) after liver transplantation has been defined histologically as a "hepatitic" pattern of injury, characterized by lymphoplasmacytic inflammation with necroinflammatory activity (NIA), comparable with findings seen in native livers. This definition, however, is difficult to apply in practice because specific histologic criteria are not clearly delineated. This study aimed to determine which histologic features correlated best with clinical and serologic features of dAIH. Index liver biopsies from patients with autoimmune-like hepatitis transplanted for non-AIH in two centers (n=35 and 20) were reviewed. Histologic features were correlated with the clinical diagnosis of AIH based on a retrospective review of clinical and serologic data, including therapeutic response. A clinical diagnosis of AIH was retrospectively assigned to 24 of 35 (68%) and 18 of 20 (90%) patients, respectively (P=0.10). In multivariate analysis, centrilobular NIA and centrilobular plasma cell (PC) ratio of 30% to 50% were independently discriminating for a clinical diagnosis of AIH (P=0.04 and 0.05, respectively). The best level of predictability (99.6%) was mathematically achieved when severe centrilobular NIA and centrilobular PC ratio of 30% to 50% were both present. A histologic pattern of centrilobular injury including increased NIA and increased PC infiltration correlates with measurements of autoimmunity in liver recipients. It could be used to segregate cases for further study and introduced into the AIH scoring systems when applied in the context of liver transplantation.

Cord around the neck syndrome

A nuchal cord (or Cord-Around-the Neck (CAN)) occurs when the umbilical cord becomes wrapped around the fetal neck 360 degrees. Nuchal cords are very common, the incidence of nuchal cord increases with advancing gestation from 12% at 24 to 26 weeks to 37% at term [1]. Most are not associated with perinatal morbidity and mortality. In some fetuses and newborns CAN may cause problems, especially when the cord is tightly wrapped around the neck. The cluster of cardiorespiratory and neurological signs and symptoms associated with unique physical features that occur secondary to tight cord-round-the-neck has been referred to as 'tCAN syndrome' (tight Cord Around the Neck Syndrome) [2]. A small number of studies have shown that nuchal cord and or tCAN can affect the outcome of delivery and may have long-term effects on the infant [3] and but as a causative factor for stillbirth it is debatable [4,5]. However, some case reports of postmortem findings on stillbirths show negative pathology reports and tight cord around the neck being the only cause of death [6]. It is the unique physical features of tCAN syndrome that distinguishes it from birth asphyxia even though there are many similarities between these two conditions. Umbilical cord abnormalities are considered as one of the causative factor for birth asphyxia. The manifestation of tCAN symptomatology seems to happen both in the presence of normal and depressed AGPAR scores [7]. Umbilical cord compression due to tCAN may cause obstruction of blood flow first in thin walled umbilical vein, while infant’s blood continues to be pumped out of baby through the thicker walled umbilical arteries thus causing hypovolemia and hypotension resulting in acidosis [8]. Anemia [9] and mild respiratory distress may occur. Some of these infants may also have facial and conjuctival petechiae [10] and rarely petechiae of the neck and upper part of the chest and skin abrasion of neck [11] where the cord was tightly wrapped and facial suffusion [12], all of which can also be seen in some postmortem findings of stillbirth infants who had tCAN [Archana Bargaje, personal communication]. If born alive, some of these infants may also be somewhat obtunded with a low tone and have transient feeding difficulties. These findings raise the possibility of transient encephalopathy, which may lead to long-term complications. A stillbirth attributed to a cord problem should have evidence of cord obstruction or circulatory compromise. Other potential causes of stillbirth need to be excluded prior to labelling cord abnormalities as the causative factor, since cord abnormalities seen in more than a third of all normal live births. The tCAN Syndrome may conceptually be similar to strangulation which may result in non lethal problems or death. The pathophysiological mechanisms of strangulation injuries (lethal and non lethal) involves venous, arterial obstruction (arterial spasm due to carotid pressure) in the neck and vagal collapse (increased parasympathetic tone) [13]. This can lead to cerebral stagnation, hypoxia, and unconsciousness, which, in turn, produces loss of muscle tone. The same pathophysiology of strangulation may possibly be applicable to tCAN syndrome in neonates. A study on potentially asphyxiating conditions and spastic cerebral palsy in infants of normal birth weight showed evidence of association of tCAN in children with quadriplegia [14]. Intermittent umbilical cord occlusion in preterm and near term sheep caused a decline in pO2 and pH, and higher PCO2 and altered brain protein synthesis/degradation [6]. Whether human fetal intermittent strangulation by tCAN have similar brain protein alterations and thus long-term effects remains to be seen. Using specific placental histologic criteria for umbilical blood flow restriction in unexplained stillbirth Parast et al [4] showed significant correlation of placental changes of “minimal histologic criteria” with cord accidents (as tCAN is part of cord accidents). Nuchal cords showed highest rates of thrombosis-related placental histopathology and fetal thrombotic vasculopathy and thrombosis seems to be highly specific for cord related stillbirths [4,5].

Malformación venosa intraósea primaria en hueso cigomático: actualización en criterios diagnósticos

Vascular anomalies include two well-differentiated conditions that are nevertheless often confused in the scientific literature: haemangiomas and vascular malformations. Primary intraosseous involvement of the zygoma is particularly rare. Moreover, most reported cases of zygomatic involvement have been categorised as “haemangioma” without appropriate diagnostic criteria. The authors describe a case of intraosseous venous malformation of the zygoma and discuss the specific clinical, histological and immunohistochemical criteria of vascular anomalies that lead to a correct diagnosis and subsequent effective treatment.

Response to Bergmann et al: Carbon 14 Birth Dating of Human Cardiomyocytes.

The letter by Bergmann and collaborators1 questions our comments2 regarding their work on 14C birth dating of human cardiomyocytes with aging.3 Three points are made in an attempt to challenge the issues we have raised, which cast serious doubts on the validity of their data on myocyte turnover with physiological aging: (1) appropriateness of the myocardial samples examined; (2) specificity of the protocol used for the isolation of myocyte nuclei; and (3) correct interpretation of the 14C measurements. As acknowledged in their letter, 6 of the 12 hearts studied, that is, 50% of the cases, had overt myocardial pathology. Surprisingly, samples collected from a patient who died of acute myocardial infarction were considered representative of normal cardiac aging. Additionally, no histological analysis was performed in the 6 “nonpathological” hearts; gross examination at autopsy was deemed to be sufficient to define the structural integrity of the myocardium. Specific clinical, anatomic, and histological criteria have to be met for the inclusion of human hearts in studies of physiological aging (Table).4,5 The approach used by Bergmann and collaborators is far from any sensible standard needed to determine the biology of human cardiac aging. View this table: Table. Inclusion Criteria for the Analysis of Physiological Myocardial Aging The authors defend the findings reported in Science 3 by citing the article that subsequently appeared in Experimental Cell Research .6 We have been criticized in the letter for ignoring this hastily published report. Our reasons for not quoting this second report must be discussed. In this work, a series of images illustrating different degrees of nuclear troponin staining have been obtained with a variety of antigen retrieval methods. These findings have been interpreted as unequivocal documentation of the expression of troponin I in myocyte nuclei, independent from the age of …

Primary cerebellar pilocytic astrocytoma with anaplastic features: a case report

Introduction Pilocytic astrocytoma (PA), a grade I glioma, rarely occurs in adults sporadically. Presenting anaplastic features within PA are uncommon and we report such a patient. Case report A 57-year-old woman presented with headache and ataxia. Magnetic resonance imaging (MRI) of the brain showed a 3 cm heterogeneous-enhancing mass harbouring cystic component in the right cerebellar hemisphere. Histological examination of the tumour exhibited that it was mostly composed of compact piloid astrocytes and microcystic changes typical of PA with scattered eosinophilic granular bodies and Rosenthal fibres. Presence of coagulative necrosis, marked pleomorphism, focal vascular endo-thelial proliferation and multiple mitosis was consistent with anaplastic features. Ki-67 was 5% and p53 stained in >50% of cells. She received post-operative radiation therapy and the tumour relapsed 8 months later. Discussion The rarity of pilocytic astrocytoma in adults accounts for difficulties in diagnosing anaplastic features and distinguishing it from glioblastoma and degenerative PA. There are specific histological criteria for diagnosis of PA with anaplastic features including presence of coagulative/pseudopalisading necrosis, hypercellularity, cytological atypia and brisk mitotic activity in addition to typical features of PA. Studies show that such tumours, specifically when necrosis presents, behave in a more aggressive manner, analogous to grade III astrocytoma, but with better behaviour than grade IV astrocytoma.