Meningeal Carcinomatosis

Meningeal carcinomatosis without gross tumour in the substance of the brain or spinal cord has been reported rarely. Two cases observed at the Victoria General Hospital, Halifax, presented a bizarre clinical picture consisting of signs of meningeal irritation without fever, and psychotic behaviour. Examination of the cerebrospinal fluid revealed low sugar concentration and increased pressure, protein and cells. In one case these cells were readily identified as malignant on stained smears. At autopsy the surfaces of the cerebral hemispheres, cerebellum and brain stem were covered by an opalescent film and on section the subarachnoid space was densely packed with malignant cells. Both primary tumours were adenocarcinomas, one originating in the gallbladder and one in the rectum. The diagnosis of meningeal carcinomatosis must be considered in patients presenting with profound mental changes and meningeal irritation without fever. Diagnosis may be confirmed by cytological examination of the cerebrospinal fluid. The primary tumour is most commonly an adenocarcinoma. There is no satisfactory treatment available.     

Choroid plexus carcinoma. Cytologic identification of malignant cells in ascitic fluid

Abdominal deposits of a choroid plexus carcinoma in a patient with a ventriculoperitoneal shunt were cytologically diagnosed by examination of ascitic fluid after regression of the primary tumor. The morphology of the malignant cells in ascitic fluid was more similar to that of mesothelial cells than to the appearance of cells from this lesion in cerebrospinal fluid.     

Bronchioloalveolar carcinoma presenting with meningeal carcinomatosis. Cytologic diagnosis in cerebrospinal fluid

The cytologic findings in a 35-year-old patient with bronchioloalveolar carcinoma who initially presented with central nervous system involvement are reported. Following the cytologic diagnosis of carcinomatous meningitis (metastatic adenocarcinoma), an open lung biopsy was performed, which confirmed the presence of a primary pulmonary neoplasm (bronchioloalveolar carcinoma). This case illustrates the importance of the cytologic diagnosis of a clinically unsuspected primary neoplasm. Further, together with three earlier reported cases, it indicates that, in young patients, tumor cells shedding into the cerebrospinal fluid can be the first indication of bronchioloalveolar carcinoma.     

The use of a panel of monoclonal antibodies in the evaluation of cytologic specimens from the central nervous system

A panel of monoclonal antibodies was tested immunohistochemically to determine the utility of such reagents in distinguishing among metastatic carcinoma, lymphoma, leukemia and primary brain tumors. The monoclonal antibodies used were: (1) a cocktail comprised of three anti-glial fibrillary acidic protein antibodies (alpha-GFAP); (2) UJ13A, a panneuroectodermal antibody; (3) B72.3, which recognizes a carcinoma-distinctive tumor-associated glycoprotein complex; and (4) 2D1, a pan-leukocyte antibody. Fifty-three specimens (21 cerebrospinal fluids, 1 ventricular fluid, 2 brain cyst fluids, 12 needle washings, 15 imprints, 1 subdural fluid and 1 post-shunt fluid) were obtained from 21 gliomas, 2 meningiomas, 1 pineoblastoma, 11 metastatic tumors, 3 lymphomas, 1 leukemia and 14 cases without tumor. alpha-GFAP stained all 21 gliomas and 5 of 5 cases containing reactive brain fragments. UJ13A had a reactivity pattern similar to that of alpha-GFAP, but also stained the meningiomas, pineoblastoma, oat-cell carcinoma and embryonal rhabdomyosarcoma. B72.3 stained all adenocarcinomas and the large-cell carcinoma. 2D1 stained lymphoma and leukemia, all inflammatory cells and 4 of 12 glioblastomas. Although no single antibody was diagnostic of a specific tumor type, this panel accurately differentiated among most primary brain tumors, metastases, leukemias and lymphomas.     

Carcinosarcoma of the gallbladder

The case of a 60-year-old woman with a five-year history of abdominal pain, jaundice, and weight loss is presented. On physical examination a hard mass on her right flank was evident. She died under unknown circumstances while she was waiting to be examined. At post-mortem examination the gallbladder was replaced by a neoplasm and there were gallstones within its lumen. Histologically, the tumour was constituted by a mixture of adenocarcinoma, squamous cell carcinoma and undifferentiated sarcoma. The diagnosis of carcinosarcoma of the gallbladder was established. A review of previously reported cases is presented too.     

Metastatic breast carcinoma in cerebrospinal fluid. A cytomorphometric study

A study was undertaken to quantitate the cellular characteristics of metastatic breast carcinoma in cerebrospinal fluid (CSF). Millipore filters of CSF from 15 patients with metastatic breast carcinoma were reviewed; 50 cells per case were evaluated when available. All cells in all cases shed singly or in loose clusters; tight balls or morulae were absent. All cells had regular, round-to-oval nuclei with finely granular chromatin. The majority of cells in all cases had single or multiple round nucleoli, granular cytoplasm with distinct borders and a mean nuclear-cytoplasmic ratio of close to 0.70. Cellular background, number of tumor cells per case, number and placement of nuclei and nuclear and cytoplasmic diameter varied both within and among the cases. There was significant variation in nuclear and cytoplasmic diameters both within and among the cases of infiltrating ductal carcinoma. Thus, the uniform appearance of the cells was due to consistent cytologic features, not to similarity in cell size. The cytologic profile of metastatic breast carcinoma is sufficiently characteristic to distinguish this tumor from other benign and malignant lesions that shed in the CSF.     

Cytologic presentation of primary leptomeningeal sarcomatosis

The cytologic findings in the cerebrospinal fluid of a 25-year-old male who presented with a diffuse neurologic disease clinically diagnosed as meningoencephalitis are described. Primary leptomeningeal sarcomatosis was subsequently diagnosed at postmortem examination. The potential value of cerebrospinal fluid cytology as a primary diagnostic tool in this rare and unusual tumor is discussed.     

Cytopathologic and clinicopathologic features of ovarian hepatoid carcinoma. A case report

BACKGROUND: Hepatoid carcinoma is a rare ovarian tumor and is thought to be a different histopathologic subtype from hepatoid-type yolk sac tumor based upon its pathologic features. However, the cytopathologic characteristics of ovarian hepatoid carcinoma (OHC) have not been reported previously. We report the clinicopathologic and cytopathologic features and immunoreactivity of a case of OHC. CASE: A 36-year-old woman presented to our department with lower abdominal pain. A left ovarian tumor was found on pelvic examination, magnetic resonance imaging and computed tomography. The tumor was diagnosed as a hepatoid carcinoma of the left ovary based upon the histopathology of the surgically resected specimen. Cytopathologic specimens from a tumor touch preparation of the tumor exhibited pleomorphic tumor cells with abundant cytoplasm. The nuclei contained rough, granular chromatin and large, prominent nucleoli. Several tumor cells were multinucleated. Tumor cells were immunoreactive for alpha-fetoprotein (AFP). Hematoxylin and eosin staining revealed that the tumor cells were in a sinusoidal pattern resembling hepatocellular carcinoma without any glandular formation. The tumor cells were negative for human chorionic gonadotropin while positive for AFP, alpha-1-antitripsin, CA-125 and carcinoembryonic antigen. CONCLUSION: Cytopathologic examination is of considerable aid in the diagnosis of OHC since cytopathologic preparations highlight the characteristic cell pleomorphism.     

腹腔镜手术意外发现胆囊癌的诊治体会

目的:探讨腹腔镜胆囊切除术中(laparoscopic cholecystectomy,LC)遇到意外胆囊癌(unexpected gallbladder carcinoma,UGC)的诊断和治疗。方法:回顾性分析我院1998年6月-2010年12月LC术中遇到的11例意外胆囊癌的临床资料。结果:术中探查结合快速病理明确诊断8例,3例术后石蜡病理证实为胆囊癌。开腹手术6例,单纯腹腔镜胆囊切除2例,3例腹腔内广泛转移,行腹腔镜胆囊姑息性切除术;结论:行LC前应加强对胆囊癌的警惕与认识。术中应常规检查胆囊标本,有怀疑者及时行冰冻切片检查。UGC确诊后应尽早开腹行根治性和扩大根治性切除术,并采取必要措施防止肿瘤种植转移。     

Granulocytic sarcoma with meningeal leukemia but no bone marrow involvement at presentation. A report of two cases with characteristic cerebrospinal fluid cytology.

Two cases occurred of granulocytic sarcoma with cerebrospinal fluid involvement but no associated leukemia on presentation. Both cases were difficult to identify by histology and were initially misdiagnosed as malignant lymphoma. The characteristic cerebrospinal fluid cytologic picture allowed the diagnosis. These cases underscore the value of cytologic examination of tumor imprints and the use of myeloid markers in panels for immunophenotyping lymphomas.     

Cerebrospinal fluid and metastasis of transitional cell carcinoma of the bladder

Two cases are presented of cerebrospinal fluid with tumor cells metastatic from transitional cell carcinomas of the bladder. They demonstrate that in spite of the rarity of transitional cell carcinoma's metastasizing to the central nervous system (0.4% to 0.6%), it is necessary to consider the bladder as the primary site and to obtain urinary cytology in such cases when the primary tumor is still unknown.     

Leiomyosarcoma of the breast: report of a case with fine needle aspiration cytologic, histologic and immunohistochemical features

BACKGROUND: Leiomyosarcoma of the breast is a rare neoplasm. We present a case of primary leiomyosarcoma of the breast in a middle-aged female in whom fine needle aspiration cytologic features suggested sarcoma. CASE: A 55-year-old female presented with a rapidly growing breast lump of 1 month's duration. On examination, an ulcerating, 12 x 10 cm tumor was seen involving the lower medial and lateral quadrants of the right breast. Fine needle aspiration cytology showed variably sized, dissociated and loosely clustered polygonal, plump and spindle cells with pale blue cytoplasm and vesicular nuclei that were round, oval or irregular. Occasional giant forms and nucleolated and mitotic cells were present. A single cluster of benign ductal cells was seen. The tumor cells did not express immunocytologic reactivity to estrogen receptor protein. A cytologic diagnosis of sarcoma was given with differential diagnoses of metaplastic carcinoma and malignant phyllodes tumor. Histologic study established the diagnosis of leiomyosarcoma. Leiomyosarcoma of the breast shows fine needle aspiration cytologic features of sarcoma, but specific tumor typing may not be possible, especially when the cytologic material is inadequate for ancillary staining required to distinguish leiomyosarcoma from metaplastic carcinoma and malignant phyllodes tumor.     

Leukocyte-derived microparticles and scanning electron microscopic structures in two fractions of fresh cerebrospinal fluid in amyotrophic lateral sclerosis: a case report

ABSTRACT: INTRODUCTION: Amyotrophic lateral sclerosis is a progressive neurodegenerative disorder characterized by degeneration of motoneuron cells in anterior spinal horns. There is a need for early and accurate diagnosis with this condition. In this case report we used two complementary methods: scanning electron microscopy and fluorescence-activated cell sorting. This is the first report to our knowledge of microparticles in the cerebrospinal fluid of a patient with amyotrophic lateral sclerosis. CASE PRESENTATION: An 80-year-old Swedish man of Caucasian ethnicity presented to our facility with symptoms of amyotrophic lateral sclerosis starting a year before his first hospital examination, such as muscle weakness and twitching in his right hand progressing to arms, body and leg muscles. Electromyography showed classical neurophysiological findings of amyotrophic lateral sclerosis. Routine blood sample results were normal. A lumbar puncture was performed as a routine investigation and his cerebrospinal fluid was normal with regard to cell count and protein levels, and there were no signs of inflammation. However, scanning electron microscopy and fluorescence-activated cell sorting showed pronounced abnormalities compared to healthy controls. Flow cytometry analysis of two fractions of cerebrospinal fluid from our patient with amyotrophic lateral sclerosis was used to measure the specific binding of antibodies to phosphatidylserine (lactadherin), CD42a, CD144 and CD45. Our patient displayed over 100 times more phosphatidylserine-positive microparticles and over 400 times more cell-derived microparticles of leukocyte origin in his cerebrospinal fluid compared to healthy control subjects. The first cerebrospinal fluid fraction contained about 50% more microparticles than the second fraction. The scanning electron microscopy filters used with cerebrospinal fluid from our patient were filled with compact aggregates of spherical particles of lipid appearance, sticking together in a viscous batter. The quantitative increase in scanning electron microscopy findings corresponded to the flow cytometry result of an increase in leukocyte-derived microparticles. CONCLUSIONS: Microparticles represent subcellular arrangements that can influence the pathogenesis of amyotrophic lateral sclerosis and may serve as biomarkers for underlying cellular disturbances. The increased number of leukocyte-derived microparticles with normal cell counts in cerebrospinal fluid may contribute to the amyotrophic lateral sclerosis inflammatory process by formation of immune complexes of prion-like propagation, possibly due to misfolded proteins. The two complementary methods used in this report may be additional tools for revealing the etiology of amyotrophic lateral sclerosis, for early diagnostic purposes and for evaluation of clinical trials, long-term follow-up studies and elucidating the pathophysiology in amyotrophic lateral sclerosis.     

Analysis of aberrant methylation on promoter sequences of tumor suppressor genes and total DNA in sputum samples: a promising tool for early detection of COPD and lung cancer in smokers

Background

Carcinoma of the gallbladder (GBC) clinically mimics benign gallbladder diseases and often escapes detection until advanced stage. Despite the frequency of cholecystectomy, diagnosis of GBC remains problematic in many situations. We sought to identify pathologic features that contribute to the difficulty in recognition of GBC.

Methods

We identified 23 patients (ranged from 45 to 86 years, male to female ratio 1:4.5) with carcinoma involving the gallbladder referred to an academic medical center over a period of 10 years for study. This includes 10 cases of primary GBC, 6 cases of metastatic tumor to gallbladder, 6 cases of directly invasive adenocarcinoma arising elsewhere in the biliary tree, and one case of unidentified origin adenocarcinoma. Primary tumors include adenocarcinoma not otherwise specified (NOS) in 6 cases, papillary adenocarcinoma in 2 cases, and single cases of undifferentiated carcinoma and combined adenocarcinoma and neuroendocrine carcinoma (NEC). Metastatic tumors to gallbladder were from a wide range of primary sites, predominantly the gastrointestinal tract.

Results

These cases illustrate seven potential pitfalls which can be encountered. These include: 1) mistakenly making a diagnosis of adenocarcinoma of gallbladder when only benign lesions such as deeply penetrating Rokitansky-Aschoff sinuses are present (overdiagnosis), 2) misdiagnosing well-differentiated invasive carcinoma with minimal disease as benign disease (underdiagnosis), 3) differentiating between primary NEC of gallbladder and metastasis, 4) confusing primary mucinous adenocarcinoma of gallbladder with pseudomyxoma peritonei from a low grade appendiceal neoplasm disseminated to gallbladder, 5) confusing gangrenous necrosis related to cholecystitis with geographic tumoral necrosis, 6) undersampling early, grossly occult disease, and 7) misinterpreting extracellular mucin pools.

Conclusions

Clinical history and a high index of suspicion are prerequisite to detecting GBC. Detection of GBC at an early stage is difficult because the symptoms mimic benign gallbladder diseases. Misinterpretation of subtle microscopic abnormalities contributes diagnostic failures in early cases. Careful attention to any evidence of mural thickening, thorough sampling, particularly in older patients, and close examination of any deeply situated glandular structures are critical. Correlations with radiographic and clinical findings are important helps to avoid misdiagnosis in this commonly resected organ.     

Advanced primary clear cell carcinoma of the vagina not associated with diethylstilbestrol

BACKGROUND: Primary vaginal clear cell carcinoma occurs in young women exposed to diethylstilbestrol (DES) in utero. Primary vaginal clear cell carcinoma not associated with DES is very rare. We report the clinicopathologic and cytopathologic features of a patient with advanced, sporadic primary vaginal clear cell carcinoma with metastases to liver, lung and paraaortic lymph nodes. CASE: A postmenopausal, 63-year-old woman presented to our department with genital bleeding. A hemorrhagic tumor found in the vagina was diagnosed as a clear cell carcinoma by cytopathologic examination of the tumor smear and by histopathologic examination of a biopsy specimen. A chest radiograph revealed multiple lung metastases, and metastases to the liver and paraaortic lymph nodes were noted on computed tomography and magnetic resonance imaging. The tumor was diagnosed as primary clear cell carcinoma of the vagina, stage IVb (FIGO) based on a normal cytopathologic examination of the cervix, endometrium and ascites; normal appearance of the uterus, ovaries and kidneys on magnetic resonance imaging; and absence of detectable tumor in the urinary tract. The patient died of respiratory failure 31 days after hospitalization. The tumor demonstrated overexpression of p53 protein and did not show microsatellite instability. CONCLUSION: This patient was the second reported Japanese woman with advanced primary vaginal clear cell carcinoma not associated with DES.     

中国人原发性胆囊肿瘤nm23H1基因遗传不稳定性的研究

采用石蜡包埋组织抽提DNA,PCR-单链构象多态性(PCR-SSCP),常规银染,Envision免疫组织化学和Leica-Qwin计算机图像分析等方法,研究人类17号染色体D17S396位点微卫星不稳定性(microsatelliteinstablility,MSI)和杂合性缺失(lossofheterozygosity,LOH),对胆囊肿瘤nm23H1蛋白表达的影响,阐明nm23H1基因遗传不稳定性与胆囊肿瘤进展的关系,为揭示nm23H1基因与肿瘤发生和转移机理提供实验依据。在本实验中,原发性胆囊癌D17S396位点遗传不稳定发生率为42.55%,明显高于良性胆囊肿瘤的13.04%,而在胆囊炎组织中,未见该位点遗传不稳定的发生;其中,LOH的发生率随组织恶性程度的增高而增加(P<0.05)。在胆囊癌中,LOH和MSI发生率与肿瘤组织分化程度具有显著差异(P<0.05);LOH的发生率,在肝脏浸润和淋巴转移组高于无肝脏浸润和无淋巴转移组,在NevinⅣ Ⅴ期高于Ⅰ Ⅱ Ⅲ期(P<0.01);而MSI发生率则相反。nm23H1蛋白阳性率在胆囊癌、胆囊良性肿瘤和炎症组织中差异显著(P<0.05);在胆囊癌中,淋巴转移组低于无淋巴转移组(P<0.01);NevinⅣ Ⅴ期低于Ⅰ Ⅱ Ⅲ期(P<0.05)。此外,计算机图像定量分析显示,在各临床病理参数影响下,nm23H1蛋白的表达强度没有差异。在胆囊癌中,LOH阳性组中nm23H1蛋白阳性率显著低于LOH阴性组,两者差异显著(P<0.05)。实验结果提示,nm23H1基因的遗传不稳定性可能是胆囊肿瘤发生、发展的一个重要机制。nm23H1基因的MSI和LOH,通过相互独立的途径调控胆囊癌的发生和转移,MSI是胆囊癌早期分子指标,LOH可作为胆囊组织恶变的判断指标,可抑制胆囊癌局部nm23H1蛋白的表达,并赋予胆囊癌高淋巴结转移、低预后的特性。提高胆囊癌局部nm23H1蛋白的表达,可减缓肿瘤的浸润转移并提高预后率。     

Cytomegalovirus associated transverse myelitis in an immunocompetent host with DNA detection in cerebrospinal fluid; a case report

ABSTRACT: BACKGROUND: Cytomegalovirus associated transverse myelitis among immunocompetent adults has been rarely reported. We report a patient presenting with clinical myelitis followed by previously unreported finding of cytomegalovirus deoxyribonucleic acid in cerebrospinal fluid. Case report A forty year old immunocompetent male presented with acute onset progressive bilateral lower limb weakness. His spinal magnetic resonance imaging findings, cerebrospinal fluid analysis and clinical picture were compatible with transverse myelitis. Polymerase chain reaction of the cerebrospinal fluid for cytomegalovirus was positive while other infectious agents were not detected by serology or polymerase chain reaction. He was treated with intravenous ganciclovir with partial clinical response. CONCLUSION: Viral genome detection in the cerebrospinal fluid was performed but negative in five out of ten reported cases of cytomegalovirus associated transverse myelitis in the immunocompetent host. In previous cases the inability to isolate the virus in cerebrospinal fluid was considered favouring an immunological mechanism leading to pathogenesis rather than direct viral toxicity but this case is against that theory. This case highlights the fact that Cytomegalovirus should be considered as an aetiological agent in patients with transverse myelitis and that the virus may cause serious infections in immunocompetent host. Therefore this report is of importance to neurologists and physicians in general.     

脑脊液检查在早产儿及足月儿细菌性脑膜炎的诊断价值

目的:评价脑脊液检查在早产儿及足月儿细菌性脑膜炎诊断中的价值。方法:选取2014年6月1日至2016年12月31日上海市儿童医院新生儿科收治的行腰椎穿刺检查的447例新生儿,回顾性分析新生儿的一般资料、脑脊液常规生化、培养等指标,根据胎龄将患儿分为早产儿167例与足月儿280例,再根据有无患发细菌性脑膜炎分为早产儿细菌性脑膜炎27例(早产儿观察组)、早产儿非细菌性脑膜炎140例(早产儿对照组)、足月儿细菌性脑膜炎38例(足月儿观察组)、足月儿非细菌性脑膜炎242例(足月儿对照组),采用受试者工作特征(ROC)曲线评估蛋白定量、白细胞计数、葡萄糖对早产儿及足月儿细菌性脑膜炎的诊断价值。结果:与同组对照组相比,足月儿观察组和早产儿观察组蛋白定量和白细胞计数均明显升高,而葡萄糖含量显著下降,且差异均具有统计学意义(P0.05);本研究65例细菌性脑膜炎患儿脑脊液培养分离出11株细菌(16.9%)。足月儿脑脊液白细胞计数、蛋白定量以及葡萄糖诊断细菌性脑膜炎的ROC曲线下面积分别为0.995、0.846、0.703。早产儿脑脊液白细胞计数、蛋白定量以及葡萄糖诊断细菌性脑膜炎ROC曲线下面积分别为0.970、0.711、0.705。结论:脑脊液白细胞计数、蛋白定量在足月儿和早产儿细菌性脑膜炎中具有较高的诊断价值。     

Adenoid cystic carcinoma of the external auditory canal. A case report with diagnosis by fine needle aspiration

BACKGROUND: Although the cytologic findings of adenoid cystic carcinoma have been reported frequently, fine needle aspiration diagnosis of adenoid cystic carcinoma of the external auditory canal has not been reported before in the English-language literature. CASE: A 70-year-old female presented with a mass occluding the external auditory canal. Fine needle aspiration cytology was performed. The smears showed hyaline globules surrounded by tumor cells. The tumor cells had uniform, round, hyperchromatic nuclei, visible nucleoli and little cytoplasm. Based on these cytomorphologic features, diagnosis of adenoid cystic carcinoma was rendered and then confirmed by histopathologic examination. CONCLUSION: This is the first cytologic report of adenoid cystic carcinoma of the external auditory canal, a rare site for this tumor.