Careful Macroscopic Examination Research Articles

Extraventricular neurocytoma.

Neurocytoma is a rare central nervous system neoplasm that usually arises in an intraventricular location (so-called Central Neurocytoma), but also exists in an extraventricular location (defined as Extraventricular Neurocytoma: EVN). Clinically EVN manifests as headache, nausea, vomiting, complex partial seizures or focal neurological deficits. In some cases, atypical signs characterizing an aggressive clinical behavior may be present. Topographically, EVN most frequently occurs as intrahemispheric (particularly in the frontal lobes), followed by the spinal cord. However, rarer sites have been described.1 Radiologically, EVN is a well-circumscribed, slow-growing neoplasm, usually hyperintense on T2-weighted MRI and isointense/hypointense with no contrast enhancement on T1-weighted MRI.2 Microscopically, EVN consists of small, round cells that show neuronal differentiation, without marked atypia and/or pleomorphism, without vascular endothelial proliferation and/or necrosis and with low mitotic and proliferation indexes. The 2016 World Health Organization classification of tumors of the central nervous system (WHO2016) assigns to EVN histological grade II.3 Immunohistochemically, the main marker to identify the neuronal nature of the neoplasm is Synaptophysin, but immunohistochemical positivity for Synaptophysin alone is not sufficient to conclude a diagnosis of EVN. In fact, there are other central nervous system tumors that may express it, including mainly: pilocytic astrocytoma, disembryoplastic neuroepithelial tumor, ganglioglioma, glioneuronal papillary tumor, some oligodendrogliomas and diffuse leptomeningeal glioneuronal tumor. For this reason, the immunohistochemistry of Synaptophysin should be supplemented with immunohistochemistry for OLIG2 (expression of this marker is usually incompatible with EVN) and molecular investigations to look for IDH mutations (in EVN, IDH must be non-mutated) and/or to look for co-deletion of chromosomes 1p and 19q (AVN must be 1p/19q non-codeleted).3 The pictures above refer to the case of an 86-year-old woman who was found unconscious on the ground at her home for no apparent reason. When she was taken to hospital, a febrile state set in but, before further investigation, she died. An autopsy was therefore carried out, which revealed acute pneumonia as the main cause of death. However, careful macroscopic examination of the formalin-fixed brain, after isolating the vessels of the polygon of Willis, revealed the presence of a 1.2 cm roundish mass at the bifurcation of the two anterior cerebral arteries (Figure1A). Figure 1 A – Macroscopic view of the Willis polygon with a mass at the emergence of the anterior cerebral arteries (arrow); B – Photomicrograph of the well- circumscribed nodular lesion with some micro calcifications (arrows) (H&E, 4x); C – High power field of the nodular lesion showing round cells, sometimes with evident nucleoli, without significant atypia and without mitosis (H&E; 60x); D – Immunohistochemistry, showing positivity for Synaptophysin.: Histological examination of this lesion showed a nodular proliferation of small, uniform round cells, sometimes with cleared cytoplasm (oligodendroglioma-like appearance), in the absence of mitosis, endothelial proliferation and/or necrosis (Figures 1B, 1C), expressing a neuronal-like immunohistochemical profile: widespread immunohistochemical positivity for S100, Synaptophysin (Figure 1D) and Neuron-specific Enolase (NSE) were detected; the proliferation index, assessed by Ki67, was less than 1%. Immunohistochemical staining was negative for: cytokeratins AE1/AE3; EMA; GFAP; OLIG2; Chromogranin; GH; Prolactin; ACTH; TSH; LH; FSH; TTF1; CD31 and CD34. Finally, also the immunohistochemical staining for R132-mutant IDH1 protein was negative. The molecular testing (FISH) for 1p/19q deletion status was not performed. The results were overall consistent with a low-grade neuronal neoplasm of the central nervous system and in particular - although the exceptional site - with an extraventricular neurocytoma.

TNM Classification: Are Cancers With Extrinsic Tongue Muscle Involvement Systematically T4a?

In the Union for International Cancer Control classification, extrinsic muscle involvement in oropharyngeal cancers is systematically defined as a T4a tumor, although the term extrinsic may incorrectly imply that these muscles are outside the tongue. Our aim was to describe the topography of extrinsic tongue muscles and show that their involvement in oropharyngeal cancers does not always correspond to T4a staging. This cadaveric study was based on dissections of the tongues of ten healthy subjects. Dissections were carried out using sections, and careful macroscopic examination with a 3.5-diopter magnifying glass allowed the identification of muscles from their origin to their termination. Imagery and histology were excluded to stay as close as possible to the clinical evaluation. The sample comprised seven men and three women, with a mean age 82years. In all the ten cases, the extrinsic muscles were located at the periphery of the tongue. The genioglossus was the only deep extrinsic muscle, extending to the periphery and under the mucous membrane of the tongue. As a result, a T1 tumor can invade the mucous membrane and affect the extrinsic muscles without transforming into a T4a tumor. As extrinsic tongue muscles are peripheral and submucosal, the use of the term "deep" is erroneous, as is the systematic usage of extrinsic muscles to define T4a oropharyngeal cancers. This study attempts to explain this error, which is recurrent in the different editions of the Union for International Cancer Control and American Joint Committee on Cancer.

Role of frozen section in intraoperative assessment of ovarian masses: a tertiary oncology center experience.

Surgical management of ovarian lesions vary considerably depending on the nature of the lesion. As the preoperative imaging and serum tumor marker levels are of limited value in the proper categorization of ovarian lesions, intraoperative pathological assessment is commonly requested for a primary diagnosis. Aim of the study is to assess the accuracy of the frozen section in the diagnosis of ovarian masses in our center and to analyze the causes of diagnostic discrepancies. In this retrospective study, frozen section diagnosis of 233 cases of ovarian masses was compared with the permanent section diagnosis. The overall accuracy of frozen section was 91.85 %. The sensitivity of frozen section diagnosis for benign, borderline and malignant tumors was 99.2, 88.46 and 82.95 % respectively. The corresponding specificity was 96.5, 93.23 and 99.3 %. There were 19 discordant cases including 18 false negative cases and one false positive case. Frozen section is an important diagnostic tool to determine the nature of ovarian masses. Careful macroscopic examination, evaluation of multiple sections along with clinical and radiological findings helps to reduce false positive and false negative results. Frozen section examination has limitations especially in cases of borderline tumors. This modality is most effective when the pathologist and surgeon are aware of the advantages and limitations.

Seek and ye shall find: the importance of careful macroscopic examination and thorough sampling in 2522 cholecystectomy specimens.

Gallbladder dysplasia and carcinoma (GBDC) vary greatly in incidence worldwide. We aimed to determine their prevalence in an Irish population, to assess the influence of tissue sampling protocols upon GBDC diagnosis, and to correlate various macroscopic and microscopic features with GBDC. We retrospectively reviewed histology reports of cholecystectomy specimens accessioned from 2000 to 2013. A total of 2522 cholecystectomy reports were reviewed, from 1860 female and 662 male patients. Male patients were significantly older (54.8 vs 46.8 years). There were 29 cases of dysplasia (1.15%) and 12 cases of carcinoma (0.48%), of which 10 were primary gallbladder cancers (0.4%). In 83.4% of cases, there was pathologic or radiologic evidence of cholelithiasis. Histologic findings included chronic (91.1%) or acute (15.4%) cholecystitis, cholesterosis (10.9%), adenomyomatous hyperplasia (2.1%), xanthogranulomatous inflammation (2.02%), and "porcelain" gallbladder (0.2%). Patients with GBDC were more likely to have a macroscopically identifiable lesion (29.4% vs 1.8%, positive predictive value, 18.18%, negative predictive value, 99.03%). Gallbladder dysplasia and carcinoma patients also had larger gallstones (median, 19 vs 12 mm) and were more likely to have adenomyomatous hyperplasia (8.8% vs 2.05%). When cases with a macroscopically identifiable lesion or clinical details suggestive of a gallbladder tumour were excluded (n = 2385), GBDC was significantly more frequently diagnosed if multiple tissue blocks had been sampled (2.91% vs 0.76%; relative risk (RR), 3.836). Rates of GBDC in Irish cholecystectomy specimens are low. The absence of a macroscopically identifiable lesion has a high (but not 100%) negative predictive value for GBDC. Sampling with more than 1 block significantly increases pickup rates of GBDC in these cases.

Posterior quadrantic disconnection maintains the activity of isolated temporal-parietal-occipital nerve tissue: neuroprotective measures in the surgical treatment of epilepsy.

Posterior quadrantic disconnection maintains the activity of isolated temporal-parietal-occipital nerve tissue: neuroprotective measures in the surgical treatment of epilepsy.

Lymphoproliferative disease of the kidney developing in fibro-inflammatory lesion

An 80-year-old man presented with continuous spike fever and night sweats. Computed tomographic scans revealed a poorly demarcated mass in the upper part of the right kidney, which was resected. At surgery, tumorous lesions were not found in the abdominal cavity. Serum IgG4 level measured after surgery was 40.1 mg/dl. Macroscopically, renal parenchyma of the upper part was replaced by an irregularly shaped grayish-white lesion of elastic, firm consistency. Histologically, the lesion consisted mostly of fibrous tissue in which small lymphoid cells, often with formation of aggregates, were evident. IgG4-positive plasma cells were few in number. Careful macroscopic examination revealed several minute nodules, which histologically consisted of large lymphoid cells, small lymphoid cells, and macrophages. These large lymphoid cells were positive for CD20 and contained Epstein-Barr virus (EBV) genome. Taken together, a diagnosis of EBV-positive B-cell lymphoproliferative disease (LPD) developing in inflammatory pseudotumor (IPT) of the kidney was made. This is the first report of B-LPD in IPT of the kidney. In addition, a presence of EBV in renal lymphoma cells has not yet been reported.

Primary Lymph Node Gastrinoma or Occult Duodenal Microgastrinoma With Lymph Node Metastases in a MEN1 Patient

Gastrinoma tissue has been found frequently in lymph nodes located near the duodenum without a known primary tumor. Therefore, it has been suggested that a primary lymph node gastrinoma exists. We report on a 38-year-old woman suffering from multiple endocrine neoplasia type 1 (MEN1) confirmed by menin gene mutation analysis. MEN1 disease started with primary hyperparathyroidism followed by Cushing disease, the detection of tumors of the pituitary, adrenal cortex, and the pancreas and also an elevated serum gastrin level. An octreotide scan revealed 4 tumors in the upper abdomen. A selective arterial calcium stimulation test located the source of the hypergastrinemia to the area of the gastroduodenal and the superior mesenteric arteries. Total pancreatoduodenectomy was performed and conventional histopathologic examination revealed a well-differentiated cystic neuroendocrine tumor of the pancreas expressing glucagon and accompanied by several microadenomas. In addition, 3 suprapancreatic lymph nodes with gastrin-positive endocrine tissue were found. None of the pancreatic microadenomas expressed gastrin and no duodenal endocrine tumor was found despite careful macroscopic examination. Only after complete embedding of the duodenal and pancreatic tissue in 65 paraffin blocks, 2 microgastrinomas (0.45 and 0.8 mm in diameter) were identified in the duodenum. It is concluded that duodenal gastrinomas that give rise to lymph node metastases may be so tiny that they are easily overlooked in a routine examination and that systematic tissue monitoring is required to identify them.

Unilateral Parotid Gland Involvement With Synchronous Multiple Basal Cell Adenomas

Basal cell adenoma (BCA) is a rare benign epithelial tumor of the salivary gland. BCA is seen most frequently in the parotid gland and less commonly in the submandibular gland and minor glands of the upper lips, oral cavity, and hard palate. Salivary gland tumors are observed as single tumors in one salivary gland. Double or multiple tumors of the salivary gland tumors are unusual and metachronous or bilateral salivary gland tumors are more observed than synchronous or unilateral tumors. The most commonly seen multiple tumor unilaterally or bilaterally is the Warthin's tumor. A 65-year-old woman with a painful, slowly enlarging mass in front of the left ear, which was present for 6 months, was evaluated. Physical examination revealed two solid and well-delineated masses in the preauricular region, which were 1.5 x 1 cm in diameter and in the tail of the parotid gland, which is 2.5 x 2 cm in diameter. Excision of the superficial lobe of the parotid gland was performed. The macroscopic examination of the specimen showed the two discrete nodular masses. Histologic examination of the two nodular solid lesions was reported as BCA. Multiple synchronous nonmembranous-type BCAs of the unilateral parotid gland is a rare entity. More extensive excision of the parotid gland tumor, careful macroscopic perioperative examination of the surgical specimen, and histologic evaluation of all surgical specimens might be necessary for reducing revision operations and surgical complications.

Omentectomy for Gynecologic Cancer: How Much Sampling Is Adequate for Microscopic Examination?

Detecting omental metastasis is crucial for staging and treatment of endometrial and ovarian carcinoma. To determine the optimal omental sampling for omentectomies to ascertain the stage of the disease in a cost-effective way. We reevaluated 258 omentectomies that were performed due to ovarian or endometrial carcinoma. A total of 116 cases were retrospectively studied, and 142 cases were prospectively studied. For prospective study, 10 to 16 blocks were sampled if the omentum showed no signs of gross tumor. Mean omental block sample frequency of 2 groups with the negative macroscopy but with or without microscopic tumor have been compared using an independent samples t test. Seven patients had no evidence of tumor metastasis on gross examination but had microscopic tumor metastasis. The mean numbers of blocks were 6.4 for patients having microscopic tumor without macroscopic involvement and 7.8 for patients having neither microscopic nor macroscopic involvement. Approximately twice as many samples were taken in the prospective analysis when compared with retrospective analysis. Two cases with microscopic omental metastasis that had no macroscopic involvement at first impression were reevaluated retrospectively and found to contain 0.3- to 0.5-cm white nodules. The rate of omental metastasis increased with the grade of the tumor (P = .005). Careful macroscopic examination is the most important step in detecting small omental metastasis. For cases with gross tumor, one section is sufficient. If a macroscopic lesion is not detectable and the patient has a high-grade tumor that will necessitate an adjuvant therapy, 3 to 5 samples seem sufficient for staging. Further studies are needed to determine the optimum sample size for tumors having a low risk of metastasis.

Staging and classification of testicular tumours: pitfalls from macroscopy to diagnosis

The accurate assessment of testicular tumours is vital for appropriate treatment to be instituted. The assessment begins at specimen receipt, as careful macroscopic examination is vital for staging, and this,...

Malignant tumors in two ancient populations: An approach to historical tumor epidemiology

The actual increase in the rate of malignant tumors has been ascribed to a higher life expectancy and the influence of various environmental factors. Herein, we present data on the frequency of malignant tumors in paleopathologically well-defined historic populations. Thereby, we looked for malignant growth affecting the skeleton in three study populations of 905 individuals that have been excavated from the necropoles of Thebes-West and Abydos, Upper Egypt covering the time period between 3200 and 500 BC and 2547 individuals that have been buried in a Southern German ossuary dating from between AD 1400 and 1800. The tissue preservation of both the Egyptian and Southern German material was excellent. All available specimens were subjected to a very careful macroscopic examination; isolated findings were also radiologically investigated. In parallel, anthropological data, such as gender and age at death, were recorded. We identified 5 cases of malignant tumors affecting the skeleton in the Egyptian material and 13 cases affecting the skeletal material from Southern Germany. In most instances, multiple osteolytic lesions with slight osteoblastic reaction are strongly suggestive for metastatic carcinoma. Few cases with poorly reactive osteolyses were most compatible with plasmacytoma. Relative tumor frequencies on an age- and sex-adjusted population basis (using a mathematic model of skeletal involvement of malignant tumors in a well-defined English study population from AD 1901 to 1905) indicated that the tumor rates were not statistically different between ancient Egyptian, the historical Southern German and the recent English reference population. These observations indicate that malignant tumors were present in spatially and temporarily different populations over the last 4000 years with an age- and gender-adjusted frequency not different from Western industrial populations of c. 100 years ago. Therefore, we conclude that the current rise in tumor frequencies in present populations is much more related to the higher life expectancy than primary environmental or genetic factors.

A practical approach to the reporting of germ cell tumours of the testis

Germ cell tumours (GCT) present many different challenges for diagnostic histopathologists and a new classification by the World Health Organization has recently introduced some new entities. The accurate diagnosis of GCT is essential for appropriate treatment. Therapy is also influenced by staging and, therefore, careful macroscopic examination is vital. Many prognostic markers have been used, many of which are still contentious. Close co-operation with both the surgical and medical teams is vital for consistent treatment and the avoidance of misunderstandings. A number of entities may mimic GCT, leading to misdiagnosis. The morphological appearances of GCT are particularly difficult to interpret if chemotherapy has already been administered. Many transformations of GCT may be seen including sarcomatous, carcinomatous and neuroendocrine malignancies. These require different treatment regimens and may arise many years after the primary excision.

Quantitative neuropathological changes in presymptomatic Huntington's disease

Morphometric studies of the tail of the caudate nucleus, the site where the pathology is first seen, were performed on 16 brain specimens collected from individuals at risk for inheriting Huntington's disease (HD). Medical records and information obtained from immediate family members indicated that all had died without symptoms of HD. Six individuals had 37 or more CAG repeats and were designated HD gene carriers, whereas 10 were determined to be non-carriers. Cell counts of the tail of the caudate nucleus revealed an increased density of oligodendrocytes among the presymptomatic HD gene carriers (mean cells/field: carriers = 40.0, noncarrier = 21.3; age, sex, repeated measure adjusted F[126] = 11.7, p = 0.0008). No statistically significant differences were found between HD carriers and noncarriers in the density of neurons (carriers = 16.9, noncarriers = 15.5), astrocytes (carriers = 27.8, noncarriers = 21.3) or microglial cells (carriers = 7.9, noncarriers = 5.6). Ubiquitin immunostaining performed in 3 gene carriers revealed intranuclear inclusions in all 3 cases, including 1, with 37 repeats, who died 3 decades before the expected age for onset of the clinical syndrome. Normal densities of other cell types and careful macroscopic examination suggest that the increase in oligodendroglial density is not a consequence of atrophy and may instead reflect a developmental effect of the HD gene. Ann Neurol 2001;49:29–34

Quantitative neuropathological changes in presymptomatic Huntington's disease

Morphometric studies of the tail of the caudate nucleus, the site where the pathology is first seen, were performed on 16 brain specimens collected from individuals at risk for inheriting Huntington's disease (HD). Medical records and information obtained from immediate family members indicated that all had died without symptoms of HD. Six individuals had 37 or more CAG repeats and were designated HD gene carriers, whereas 10 were determined to be non-carriers. Cell counts of the tail of the caudate nucleus revealed an increased density of oligodendrocytes among the presymptomatic HD gene carriers (mean cells/field: carriers = 40.0, noncarrier = 21.3; age, sex, repeated measure adjusted F[126] = 11.7, p = 0.0008). No statistically significant differences were found between HD carriers and noncarriers in the density of neurons (carriers = 16.9, noncarriers = 15.5), astrocytes (carriers = 27.8, noncarriers = 21.3) or microglial cells (carriers = 7.9, noncarriers = 5.6). Ubiquitin immunostaining performed in 3 gene carriers revealed intranuclear inclusions in all 3 cases, including 1, with 37 repeats, who died 3 decades before the expected age for onset of the clinical syndrome. Normal densities of other cell types and careful macroscopic examination suggest that the increase in oligodendroglial density is not a consequence of atrophy and may instead reflect a developmental effect of the HD gene.

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Infection maternofœtale disséminée à Candida albicans et grande prématurité

Background. — Despite the frequency of vaginal yeast colonization, serious candidiasis infections in pregnant patients or neonates remain rare. Four cases of disseminated congenital candidiasis in very preterm infants are reported. Case reports. — Congenital Candida albicans infection has been diagnosed in four very preterm infants. In three cases, the mothers had intrauterine devices in place throughout pregnancy. A careful macroscopic examination of the umbilical cord and placenta after birth has allowed an early management strategy in three cases. In all cases, a serious infectious alveolitis occured. A pronounced increase in white blood cells (> 50,000/mm 3) and high levels of both segmented neutrophil and band cells, despite the frequent normality of the CRP, constituted other features. Infection was controlled by parenteral amphotericin B or fluconazole. In one case, serious thrombocytopenia occurred after the first amphotericin B injection requiring substitution for fluconazole. The outcome was unfavourable in two cases with an extensive periventricular leukomalacia. Conclusion. — Congenital candidiasis in these four very preterm neonates has several features in common: intrauterine contraceptive device during pregnancy, characteristic chorioamnionitis and funisitis, high WBC count, infectious alveolitis. Fluconazole as alternative to amphotericine B therapy is proposed.

Small coronary vessel disease and sudden coronary death.

In an attempt to determine the importance of atherosclerosis in medium-sized coronary arteries, the hearts of 20 patients dying of cardiac disease, within 24 hours of the onset of symptoms, were compared with 19 controls. Post-mortem coronary angiograms were performed and the coronary arteries dissected in detail. Severe stenoses, or complete occlusions, were present in 34 of 80 major coronary arteries in the sudden cardiac death (SCD) group and 5 of 76 in the controls. Medium-sized branch vessels were severely stenosed or occluded in 20.5 per cent (37 of 180 vessels) in the SCD group and 6.4 per cent (11 of 171 vessels) in the controls. Forty of the 48 diseased branch vessels arose from the left anterior descending artery. In the SCD group, 18 patients died from major coronary artery atheroma, one from hypertensive heart disease and only one from disease of a branch vessel. We conclude that, in most cases of SCD, careful macroscopic examination of the major coronary vessels will provide an adequate explanation for death. Detailed dissection of all medium-sized branch vessels is unlikely to be of value as a routine procedure but, at the very least, pathologists should identify and dissect the first septal and diagonal branches of the left anterior descending artery in every post-mortem.

Routine culturing for clostridium difficile?

In order to determine whether routine culturing for Clostridium difficile was warranted or whether culturing a selected group of patients was adequate, we conducted a prospective trial of culturing all stool specimens for C. difficile. A total of 408 specimens from 297 patients was studied. Two hundred and eighteen stool specimens from 169 patients were selected on the basis of fulfilling one or more of the following criteria; (i) the stools were loose or watery; (ii) leukocytes and/or red cells were seen on direct microscopic examination; (iii) there was a history of antibiotic therapy; (iv) there was a diagnosis or history of inflammatory bowel disease. Fifty-three stools from 33 (19.5%) of these patients either yielded C. difficile by culture or had C. difficile cytotoxin demonstrable in fecal extracts. C. difficile was cultured in only one of 190 stools from the remaining 128 patients. Hence routine culturing of all stool specimens does not appear warranted provided that an accurate clinical history can be obtained and a careful macroscopic and microscopic examination is carried out.

Feeding studies on sodium cyclamate, saccharin and sucrose for carcinogenic and tumour-promoting activity

Groups of 50 female Swiss mice were fed for 18 months on a standard diet containing sucrose (10%), sodium cyclamate (5%) or saccharin (5%), while 100 control mice were fed on the standard diet alone. The survival times were comparable in all groups and no acute toxic effects were encountered. No local tumours in the gastro-intestinal tract, nor excess incidence of distant tumours, were found in animals fed on the various sweeteners. The mice fed on the diet containing 10% sucrose gained more weight than animals in the other groups, but did not show an increased incidence of neoplasms. Comparable groups of mice were given a single intragastric instillation of 50 μg benzo[ a]pyrene in 0·2 ml polyethylene glycol 400, 7 days before the start of feeding of the different test diets. Some mice in all these groups developed, as expected, benign and malignant neoplasms of the forestomach epithelium, but treatment with the sweetening agents had no obvious effect on the incidence, number or histological type of these or of any other type of neoplasm. No neoplasms of the urinary bladder were seen on careful macroscopic examination of mice at necropsy; the bladders were not examined microscopically. It is concluded that, under the experimental conditions described, the three sweeteners examined showed no carcinogenic or tumour-promoting activity.

Congenital Malformations of the Eye

Ophthalmic pathologists today are in a position to make anatomic diagnoses of conditions about which they knew little or nothing a decade ago. Recent clinical, epidemiologic, and laboratory investigations have established the cause of some congenital malformations and provided clues as to the pathogenesis of others. These advances have enabled the pathologist to interpret the potential diagnostic significance of certain combinations of anatomic changes as, for example, the association of aniridia and congenital cataract with Wilms' tumor. While a complete autopsy is always more revealing than examination of a single organ, careful macroscopic and microscopic examination of the eyes alone may provide enough information for a presumptive diagnosis. The ocular lesions observed in the 13-15 trisomy syndrome, Lowe's syndrome, and on the congenital rubella syndrome provide particularly good examples.