Journal of Pathology and Translational Medicine

Case Studies

Cytologic Diagnosis of Metastatic Alveolar Rhabdomyosarcoma in Cerebrospinal Fluid: A Case Report: Bobae Shim, Jiwon Koh, Ji Hye Moon, In Ae Park, Han Suk Ryu; J Pathol Transl Med. 2018;52(4):262-266. Published online June 14, 2018; DOI: https://doi.org/10.4132/jptm.2018.05.15

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Rhabdomyosarcoma is a malignant soft tissue tumor which shows skeletal muscle differentiation. Leptomeningeal metastasis can occur as a late complication, but currently there are no reports that have documented the cytologic features in cerebrospinal fluid (CSF). We report a case of metastatic alveolar rhabdomyosarcoma diagnosed in the CSF of a 28-year-old male who was originally diagnosed with rhabdomyosarcoma on the neck, and that went through systemic therapy. The tumor was positive for anaplastic lymphoma kinase, but progressed despite additional therapy with crizotinib. The CSF specimen revealed small round cells, large atypical cells with abundant cytoplasm and eccentric nuclei, and cells with horseshoe-shaped nuclei. These cytologic findings were in agreement with previous literature and well-correlated with histopathology. This is the first report to document the cytologic feature of rhabdomyosarcoma in CSF. In many cases it is difficult to perform ancillary tests in a CSF specimen and cytopathologists should be aware of the cytomorphologic characteristics to avoid misdiagnosis.

Citations

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A Review of Effusion Cytomorphology of Small Round Cell Tumors
Lucy M. Han, Christopher J. VandenBussche, Mads Abildtrup, Ashish Chandra, Poonam Vohra
Acta Cytologica.2022; 66(4): 336. CrossRef
Cytologic diagnosis of metastatic embryonal rhabdomyosarcoma in cerebrospinal fluid: A case report
Muxia Yan, Ying Wu, Jianqing Xia, Xiaohong Zhang, Yiqian Wang
Diagnostic Cytopathology.2021;[Epub] CrossRef
Effusion cytology of epithelioid rhabdomyosarcoma
Andrew A. Renshaw, Edwin W. Gould
Diagnostic Cytopathology.2019; 47(10): 1042. CrossRef

Liquid-Based Cytology of the Cerebrospinal Fluid in a Case of Cryptococcal Meningitis: Jiwoon Choi, Se Hoon Kim; J Pathol Transl Med. 2018;52(1):61-63. Published online October 26, 2017; DOI: https://doi.org/10.4132/jptm.2017.06.13

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Abstract PDF

Cryptococcus neoformans is the most common microorganism found in cerebrospinal fluid (CSF) cytology and causes life-threatening infections in immunocompromised hosts. Although its cytomorphologic features in conventional smear cytology have been well described, those in liquid-based cytology have rarely been. A 73-year-old woman with diffuse large B-cell lymphoma presented with mental confusion and a spiking fever. To rule out infectious conditions, CSF examination was performed. A cytology slide that was prepared using the ThinPrep method showed numerous spherical yeast-form organisms with diameters of 4–11 μm and thick capsules. Occasional asymmetrical, narrow-based budding but no true hyphae or pseudohyphae were observed. Gomori methenamine silver staining was positive. Cryptococcosis was confirmed in blood and CSF through the cryptococcal antigen test and culture. Liquid-based cytology allows for a clean background and additional slides for ancillary testing, facilitating the detection of microorganisms in CSF specimens, particularly when the number of organisms is small.

Citations

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Unraveling Capsule Biosynthesis and Signaling Networks in Cryptococcus neoformans
Eun-Ha Jang, Ji-Seok Kim, Seong-Ryong Yu, Yong-Sun Bahn, Teresa R. O’Meara
Microbiology Spectrum.2022;[Epub] CrossRef
Cerebrospinal fluid pleocytosis in immunocompromised patients: Can it be Cryptococcus
Ridhi Sood, Ruchita Tyagi, Pavneet Selhi, Harpreet Kaur, Neena Sood
Diagnostic Cytopathology.2020; 48(2): 164. CrossRef
Special Staining of the Liquid-Based Cytopathology Test in Bronchoalveolar Lavage Fluid for Diagnosis of Invasive Pulmonary Aspergillosis with Nonneutropenic Patients
Yue Hu, Lin Zheng, Deng Pan, Lei Shao, Xianfa Xu, Yiming Yu, Qidong Zhuang, Zaichun Deng, Zhongbo Chen
Canadian Respiratory Journal.2020; 2020: 1. CrossRef
Sensitivity of Cerebrospinal Fluid Cytology for the Diagnosis of Cryptococcal Infections
Kelsey E McHugh, Melanie Gersey, Daniel D Rhoads, Gary W Procop, Yaxia Zhang, Christine N Booth, Charles D Sturgis
American Journal of Clinical Pathology.2019; 151(2): 198. CrossRef
Cryptococcal Capsules in Cerebrospinal Fluid Visible on Hemocytometer
Zen Kobayashi, Yuriko Hirota, Shuzo Shintani
Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques.2018; 45(6): 700. CrossRef

Original Articles

Diagnostic Accuracy of Cerebrospinal Fluid (CSF) Cytology in Metastatic Tumors: An Analysis of Consecutive CSF Samples: Yoon Sung Bae, June-Won Cheong, Won Seok Chang, Sewha Kim, Eun Ji Oh, Se Hoon Kim; Korean J Pathol. 2013;47(6):563-568. Published online December 24, 2013; DOI: https://doi.org/10.4132/KoreanJPathol.2013.47.6.563

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Abstract PDF

Background

Cerebrospinal fluid (CSF) examination can be used to verify the presence of primary malignancies as well as cases of central nervous system (CNS) metastasis. Because of its importance, there have been several studies concerning the sensitivity of CSF cytology. To determine the practical use and reproducibility of diagnoses based on CSF cytology, we evaluated this test by analyzing cytology results from consecutive CSF samples.

Methods

Between July 2010 and June 2013, 385 CSF cytology samples from 42 patients were collected. The samples were gathered using a ventricular catheter and reservoir. CSF cytology of all patients was examined more than two times with immunocytochemistry for cytokeratin.

Results

Primary neoplastic sites and histologic types of patients' metastatic cancer were diverse. The overall sensitivity for detecting malignancy was 41.3%. Even within short-term intervals, diagnoses frequently changed.

Conclusions

Our results were inconsistent, with low sensitivity, when compared to the results of previous studies. However, CSF evaluation can still provide valuable diagnostic and prognostic information because adjuvant treatments are now routinely performed in patients with CNS metastasis. Negative CSF cytology results should not be ignored, and continuous CSF follow-up is essential for following the clinical course of patients with metastatic cancer involving the CNS.

Citations

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Numb cheek syndrome in breast cancer: a case report
Zhibin Tan, Si Ying Tan
Frontiers in Oncology.2024;[Epub] CrossRef
Utility and performance of cell blocks in cerebrospinal fluid cytology: Experience at two teaching hospitals
Hyeji Yoon, Constance V. Chen, Vimal Krishnan, Jill Grochowski, Gioia Iezza, Poonam Vohra, Ronald Balassanian, Nancy Y. Greenland
Cancer Cytopathology.2024;[Epub] CrossRef
Body fluids
Shyam H. Nemade, Meherbano M. Kamal
Indian Journal of Pathology and Microbiology.2023; 66(1): 75. CrossRef
Standardizing a volume benchmark for cerebrospinal fluids for optimal diagnostic accuracy
David Kim, Susan A. Alperstein, Momin T. Siddiqui
Diagnostic Cytopathology.2021; 49(2): 258. CrossRef
Evaluating Infectious, Neoplastic, Immunological, and Degenerative Diseases of the Central Nervous System with Cerebrospinal Fluid-Based Next-Generation Sequencing
Konstantinos I. Tsamis, Hercules Sakkas, Alexandros Giannakis, Han Suk Ryu, Constantina Gartzonika, Ilias P. Nikas
Molecular Diagnosis & Therapy.2021; 25(2): 207. CrossRef
Imaging of Intraspinal Tumors
Luke N. Ledbetter, John D. Leever
Radiologic Clinics of North America.2019; 57(2): 341. CrossRef
Isolated leptomeningeal carcinomatosis and possible fungal meningitis as late sequelae of oesophageal adenocarcinoma
Richard Dumbill, Sanja Thompson, Heiko Peschl, GDH Turner, Charles Woodrow
BMJ Case Reports.2019; 12(11): e230117. CrossRef
Cytomorphological and immunocytochemical examinations of cerebrospinal fluid in primary and metastatic brain lesions
M. V. Savostikova, L. Ya. Fomina, E. S. Fedoseeva, E. Yu. Furminskaya
Onkologiya. Zhurnal imeni P.A.Gertsena.2018; 7(1): 28. CrossRef
Metastatic Breast Carcinoma in Cerebrospinal Fluid: A Cytopathological Review of 15 Cases
Rema Rao, Syed A. Hoda, Alan Marcus, Rana S. Hoda
The Breast Journal.2017; 23(4): 456. CrossRef
Clinicocytological analysis of cases with positive cerebrospinal fluid in our hospital
Nozomi IWAMOTO, Mitsuaki ISHIDA, Akiko KAGOTANI, Nozomi KASUGA, Muneo IWAI, Yuji HAYASHI, Namie ARITA, Yoshimitsu MIYAHIRA, Ryoji KUSHIMA
The Journal of the Japanese Society of Clinical Cytology.2016; 55(5): 291. CrossRef

Value of Additional Immunocytochemical Stain for Cytokeratin in the Diagnosis of Leptomeningeal Involvement of Metastatic Carcinoma.: Junjeong Choi, Se Hoon Kim; Korean J Pathol. 2011;45(5):516-519.; DOI: https://doi.org/10.4132/KoreanJPathol.2011.45.5.516

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Abstract PDF: BACKGROUND
The purpose of this study was to describe potential pitfalls in the diagnosis of metastatic adenocarcinoma in cerebrospinal fluid (CSF) and to suggest additional work in association with cytokeratin immunocytochemistry for the proper diagnosis, especially in the specimens with low cellularity.
METHODS
We collected 267 cytologic specimens of CSF from patients, who were diagnosed over a 9-month period. Each of the individual samples were divided into half the sample size and processed via both, ThinPrep (TP) with Papanicolau stain and cytocentrifugation-based preparation (cytospin, CP) with immunocytochemical stain for cytokeratin.
RESULTS
Amongst the 267 cases, 45 cases from 22 patients were diagnosed to be positive for metastasis adenocarcinoma in CSF. TP with Papanicolau stain showed satisfactory cytomorphology when compared with specimen of CP preparation and cytokeratin immunocytochemical staining. All the TP processed cases belonged to satisfactory/superior categories based on the assessment of technical artifact, which potentially helps in decreasing diagnositc errors. However, in 10 out of 45 cases, diagnostic atypical cells were present only in one of the two slides.
CONCLUSIONS
Immunocytochemical stain for cytokeratin along with TP processed specimen helps in decreasing potential diagnostic errors in the cytological diagnosis of metastatic carcinoma in CSF specimen.

The Cytology for Leukemic Cells in Cerebrospinal Fluid; Comparison of Conventional Cytology with Liquid-Based Cytology.: Changyoung Yoo, Youn Soo Lee, Chang Suk Kang, Sang In Shim, Kyo Young Lee; Korean J Pathol. 2009;43(2):164-170.; DOI: https://doi.org/10.4132/KoreanJPathol.2009.43.2.164

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Abstract PDF: BACKGROUND
The cytological examination of cerebrospinal fluid (CSF) using conventional cytology with a cytocentrifuge (cytospin) is an important method for evaluating the involvement of leukemia in the CNS. Liquid-based cytology (LBC) is now a widely used cytological method not only for gynecological and non-gynecological specimens, but its application to CSF for the identification of leukemic cell has not yet been reported. In this study, we tried to compare conventional cytology with using a cytospin with LBC and Papanicolaou (Pap) staining. We also examined the modified LBC with Wright staining to assess whether this modified method can be useful for diagnosing Leukemia.
METHODS
We studied 30 cases of CSF that were obtained from 16 patients, including 17 cases of acute myeloid leukemia, 12 cases of acute lymphoblastic leukemia and 1 case of diffuse large B cell lymphoma. We applied conventional cytology with a cytocentrifuge (cytospin), LBC with Pap staining and modified LBC with Wright staining.
RESULTS
The morphological features of the LBC with Pap staining showed difficulty for interpretation when compared with conventional cytology with a cytospin, and mainly because of cellular shrinkage. The modified LBC with Wright staining showed good morphological features.
CONCLUSIONS
We suggest that modified LBC with Wright staining may be useful for examining CSF.

Analysis of Leptomeningeal Metastasis in Cerebrospinal Fluid Cytology.: Ilseon Hwang, Joon Seon Song, Gyungyub Gong; Korean J Pathol. 2009;43(1):63-67.; DOI: https://doi.org/10.4132/KoreanJPathol.2009.43.1.63

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Abstract PDF: The confirmative diagnosis of leptomeningeal metastasis depends on detecting malignant cells on the cytologic examination of cerebrospinal fluid (CSF). The presence of leptomeningeal metastasis is a very important factor to determine the aggressiveness of treatment. We analyzed 273 cases that were diagnosed as malignancies on the CSF cytology. The most common metastatic carcinoma was lung cancer (76 cases, 27.8%). There were 49 cases (17.9%) and 40 cases (14.7%) of breast and stomach cancers, respectively. There were 49 cases (17.9%) of lymphoma and 40 cases (14.7%) of leukemia. There were 19 cases of other types of cancer (6.9%). For the cases of primary lung cancer, there were 60 cases (78.9%) of adenocarcinoma and 7 cases (9.2%) of squamous cell carcinoma, but only 4 cases (5.3%) of small cell carcinoma. For the case of breast cancer, all of those were invasive ductal carcinoma and 25 cases (51.0%) were grade 3. Diffuse large B-cell lymphoma was the most common type of all metastatic lymphomas (22 cases, 44.9%) and lymphoblastic lymphoma was the second most common (8 cases, 16.3%). In our hospital, the most common leptomeningeal metastasis was adenocarcinoma of the lung, and breast cancer and lymphoma were the second most common. On CSF cytology, malignancies that have a tendency towards CSF metastasis should be carefully examined for to select the proper treatment.

Review

Cytologic Findings of Cerebrospinal Fluid.: So Young Jin; Korean J Cytopathol. 2008;19(2):86-98.; DOI: https://doi.org/10.3338/kjc.2008.19.2.86

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Abstract PDF: Cerebrospinal fluid (CSF) cytology is based on the cytopathologic findings of other body fluids. However, CSF's cytologic features are less familiar to physicians than are those of the other body fluid's cytology because of the small number of cases. The low overall diagnostic accuracy and the presence of false positivity still remain as problems. The incidence of lymphoreticular malignancies and metastatic carcinomas are rather higher than that of primary brain tumors. In this review, the characteristic cytologic findings of conventional CSF cytology are reviewed along with a brief note on the technical preparation and diagnostic pitfalls.

Original Articles

Cytologic Analysis of Malignant Tumor Cells in Cerebrospinal Fluid.: Jae Hee Suh, Gyungyub Gong, Shin Kwang Khang, On Ja Kim; Korean J Cytopathol. 1998;9(1):21-28.

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Abstract PDF: Cytologic evaluation of cerebrospinal fluid(CSF) is an effective tool in diagnosing many disorders involving the central nervous system(CNS). CSF examination has been found to be of particular value in the diagnosis of metastatic carcinoma, lymphomatous or leukemic involvement of CNS and certain primary CNS tumors. As a survey of metastatic tumors to CSF and an evaluation of the preparation techniques increasing cellular yield in our laboratory, 713 CSF specimens examined between July 1995 and April 1997(1 year 10 months), were reviewed. There were 75 positive and 5 suspicious cases, the latter have had no evidence of tumors clinically. Primary tumors of 75 positive cases were classified as follows; 4(5.3%) as primary brain tumors, 40(53.3%) as secondary carcinomas, 13(17.3%) as leukemias, and 18 (24.0%) as lymphomas. The most common primary site of metastatic carcinomas was the lung in 17 cases(42.5%) followed by the stomach in 13(32.5%), breast in 8 (20.0%), and unknown primary in 2(5.0%). Four primary brain tumors were 3 cerebellar medulloblastomas and a supratentorial primitive neuroectodermal tumor (PNET). All 40 metastatic carcinomas were adenocarcinoma presented as single cells or cell clusters. Although signet ring cells were frequent in the cases of gastric primary cancers, no significant cytologic differences according to the primary site were observed. The cytologic features of leukemia and lymphoma were characterized by hypercellular smears presenting as individual atypical cells with increased N/C ratio, presence of nucleoli, and nuclear protrusions. In medulloblastomas and PNET, the principal cytologic findings were small undifferentiated cells arranged singly or in loose clusters with occasional rosettoid features. This study suggests that the CSF cytology is useful in the diagnosis of malignancy, especially metastatic extracranial tumors and the diagnostic accuracy can be improved by increasing cellular yield using cytocentrifuge.

Cytologic Features and Distribution of Primary Sites of Malignant Cells in Cerebrospinal Fluid .: Yeon Mee Kim, Mi Yeong Jeon, Je Geun Chi; Korean J Cytopathol. 2000;11(2):65-73.

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Abstract PDF: Cytologic evaluation of cerebrospinal fluid(CSF) is an effective mean for diagnosing many disorders involving the central nervous systems(CNS). One of the most important reasons for cytologic examination of CSF is to detect metastatic or primary neoplasms of the CNS. We did a retrospective study of 1,438 CSF specimens obtained between 1992 and 1996. A total of 1,205 adult and 233 pediatric CSF specimens from 947 patients were accessed at the Department of Pathology of Seoul National University Hospital and Children's Hospital, respectively. Among 1,438 CSF cytology specimens, 169 cases(11.8%, 77 patients) including 135 adult cases(59 patients) and 34 pediatric cases(18 patients) were positive for malignant cells. Diagnoses included 60 metastatic carcinomas(adult, 60; pediatric, 0); 46 malignant lymphomas(adult, 44; pediatric, 2); 21 leukemias(adult, 20; pediatric, 1); 4 retinoblastomas(adult, 0; pediatric 4); 2 rhabdomyosarcomas(adult, 0; pediatric, 2); 1 multiple myeloma(adult, 1; pediatric, 0), and 35 primary CNS neoplasms(adult, 10; pediatric, 25). The most commonly identified metastatic carcinomas in adults were adenocarcinoma. Their primary sites were the lung, gastrointestinal tract, and breast in order of frequency. The most common primary CNS neoplasm in children was medulloblastoma.

Case Report

Primary Leptomeningeal Glioblastomatosis Detected in Cerebrospinal Fluid Cytology: A Case Report.: Ki Seok Jang, Si Hyong Jang, Young Soo Song, Moon Hyang Park; Korean J Cytopathol. 2005;16(2):110-114.

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Abstract PDF: Primary leptomeningeal glioblastomatosis is a rare and fatal tumor of the central nervous system, the condition is characterized by diffuse infiltration of the tumor in the meninges without evidence of primary tumor within the brain or spinal cord. We reported an unusual case of leptomengial glioblastomatosis, which was detected by the consecutive cerebrospinal fluid (CSF) cytology with application of immunohistochemistry, in addition to its cytologic findings. A healthy 21 year old man, who was enlisted in the army, presented with a stuporous mental state and diffuse enhancement of meninges without evidence of primary mass lesion in the brain and spinal cord on magnetic resonance imaging(MRI). CSF cytology showed small loose clusters of tumor cells with single cells and lymphocytes. The tumor showed variable pleomorphism with coarse chromatin, irregular nuclear membranes and multi lobated nuclei. On immunohistochemical staining, the tumor cells were founded to be positive for GFAP. In conjunction with radiologic findings, brain biopsy confirmed the diagnosis of leptomenigeal glioblastomatosis. The use of immunohistochemistry is helpful in confirming CSF cytologic diagnosis in patients with primary leptomeningeal glioblastomatosis.

Original Articles

Evaluation for Cytopreservability of Manual Liquid-Based Cytology Liqui-PREP(TM) and its Application to Cerebrospinal Fluid Cytology: Comparative Study with Cytospin.: Gyeongsin Park, Kyungji Lee, Chan Kwon Jung, Dae Hyoung Lee, Bin Cho, Youn Soo Lee, Sang In Shim, Kyo Young Lee, Chang Suk Kang; Korean J Cytopathol. 2007;18(1):46-54.

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Abstract PDF: Cerebrospinal fluid (CSF) cytology is an effective tool for evaluating diseases involving the central nervous system, but his technique is usually limited by its low cellularity and poor cellular preservation. Here we compared the manual liquid-base Liqui-PREPTM (LP) to the cytospin (CS) with using a mononuclear cell suspension and we applied both methods to the CSFs of pediatric leukemia patients. The cytopresevability, in terms of cell yield and cell size, and the clinical efficacy were evaluated. When 2000 and 4000 mononuclear cells were applied, LP was superior to CS for the cell yield, 16.8% vs 1.7% (P=0.001) and 26.2% vs 3.5% (P=0.002), respectively. The mean size of the smeared cells was 10.60 micrometer in the CS, 5.01 micrometer in the LP and 6.50 micrometer in the direct smear (DS), and the size ratio was 1.7 (CS to DS), 0.8(LP to DS) and 2.1 (CS to LP), respectively. As compared to the cells in the DS, the cells in the CS were significantly enlarged, but those in the LP were slightly shrunken. Upon application to 109 CSF samples, 4 were diagnosed as positive for leukemia (positive), 4 had atypical cells and 101 were negative by CS; 6 were positive, one had atypical cells and 102 were negative by LP. For six cases, in which 4 were positive for leukemia and 2 of 4 had atypical cells by CS, they were positive by LP and they were also confirmed as positive according to the follow-up study. Three cases diagnosed as atypical cells (two by CS and one by LP), were confirmed as negative. In conclusion, these results suggest that LP is superior to CS for the cytopresevability and for rendering a definite diagnosis of cerebrospinal fluid.

Carcinomatous Meningitis as the Initial Manifestation of Primary Stomach Cancer.: Gui Ohk Yoon, Ill Hyang Ko; Korean J Pathol. 1988;22(2):208-210.

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Abstract PDF: Meningeal carcinomatosis as the initial clinical manifestation of a tumor is a very rare event and difficult to make diagnosis. Lumbar puncture is a single and useful diagnostic method, and meticulous cytologic study of cerebrospinal fluid specimen is needed for correct diagnosis. A case of meningeal carcinomatosis diagnosed by cytologic study of CSF and later confirmed primary carcinoma of the stomach by, fiberscopic biopsy is briefly presented. Meningeal signs and symptoms were the primary clinical manifestation in case.

A Histopathologic Study of Mammary Dysplasia.: Je G Chi, Chul Woo Kim, Yeon Lim Suh; Korean J Pathol. 1988;22(2):123-130.

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Abstract PDF: "Mammary dysplasia" and "fibroadenoma" represent almost all benign breast disease presenting with breast lumps. Mammary dysplasia comprises variable non-specific changes of stroma and epithelium, but fibroadenoma has been classified as a benign neoplasm, although both features not uncommonly coexist. Authors performed a blind microscopic review of 660 cases of benign breast lesions and the results are as followings. 1. Only 27.9% of all cases consisted of pure fibroadenoma in contrast to 57.5% in the original diagnosis. 2. Fibrocystic disease frequently contained foci of fibroadenoma showing varied stages (68.3%), and the younger age group presented more wide areas of fibroadenoma. 3. The most common feature of the fibrocystic disease was fibrosis, followed by cystic change, adenosis and epithelial hyperplasia in order of frequency. 4. Fibroadenoma may be a form of a spectrum produced by hormonal imbalance, and better classified as a nonneoplastic lesion.

Spinal Fluid Cytology of Retinoblastoma.: Je G Chi, Chul Woo Kim, Yeon Lim Suh; Korean J Pathol. 1988;22(2):123-130.

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Abstract PDF: Of all the primary central nervous system tumors, the medulloblastoma, glioblastoma multiforme, ependymoma and pineal germinoma tend to exfoliate in the cerebrospinal space. With all other types of the tumor, abnormal cells may seldom be definitely identified in the cerebrospinal fluid. Up to now the tumor cells have been rarely found in CSF cases of retinoblastoma. We have experienced a case of advanced retinoblastoma that showed exfoliated cells in spinal fluid.

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