ASC 58th Annual Scientific Meeting

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1 Effusion Cytology: Charting a course through and navigating the waters Michael H. Roh, MD, PhD Claire W. Michael, MD University of Michigan Medical School

2 Conflict of interest The presenters have no conflicts of interest to disclose.

3 Common Malignancies in Effusions Most patients with a malignant effusion have a known cancer history. Occasionally, a malignant effusion can represent the initial indication of an underlying malignancy. MONTE, S. A. et al (1987) Acta Cytologica, 31, PEREIRA,T.C. et al (2006) Advances in Anatomic Pathology, 13,

4 Common Malignancies in Effusions Positive effusion as an initial diagnosis of a malignancy: Studies based on autopsy confirmation Pleural effusions (N=143): 60.1% Peritoneal effusions (N=215): 57% DIBONITO, L. et al. (1992) Acta Cytologica, 36, DIBONITO, L. et al. (1993) Acta Cytologica, 37,

5 Common Malignancies in Effusions A malignant effusion can sometimes indicate the presence of a distinct second primary in light of a known cancer history.

6 Common Malignancies in Effusions The importance of effusion cytology lies in its increased sensitivity compared to serosal biopsy. 385 patients with concurrent cytology & biopsy 109 (28%) had final diagnosis of malignancy Positive cytology in 71% Positive biopsy in 45% Combined sensitivity = 82% NANCE, K.V., et al (1991) Modern Pathology, 4,

7 Common Malignancies in Effusions In patients with an unknown primary, the following clinical features can serve as guides to the diagnosis of a malignant effusion: Age Sex Serous cavity involved JOHNSTON, W. W. (1985) Cancer, 56, PEREIRA,T.C. et al (2006) Advances in Anatomic Pathology, 13,

8 Common Malignancies in Effusions Common causes of malignant pleural effusions in men: Carcinomas Lung Gastrointestinal tract Pancreaticobiliary tree Genitourinary tract Lymphoma/Leukemia

9 Common Malignancies in Effusions Common causes of malignant pleural effusions in women: Carcinomas Lung Breast Female genital tract (Müllerian) Gastrointestinal tract Pancreaticobiliary tree Lymphoma/Leukemia

10 Common Malignancies in Effusions Common causes of malignant peritoneal effusions in men: Carcinomas Gastrointestinal tract Pancreaticobiliary tree Genitourinary tract Lymphoma/Leukemia

11 Common Malignancies in Effusions Common causes of malignant peritoneal effusions in women: Carcinomas Female genital tract (Müllerian) Gastrointestinal tract Pancreaticobiliary tree Breast Lymphoma/Leukemia

12 Common Malignancies in Effusions Common causes of malignant pericardial effusions in men/women: Carcinomas Lung Breast Lymphoma/Leukemia Mesothelioma

13 Common Malignancies in Effusions The diagnosis of carcinoma is most easily made upon recognition of a foreign population of cells apart from the background mesothelial cells and histiocytes. The most common carcinoma to present in effusions is adenocarcinoma.

14 Metastatic Adenocarcinoma - Foreign Population

15 Metastatic Adenocarcinoma - Foreign Population

16 Metastatic Adenocarcinoma Uniform Population

17 Metastatic Adenocarcinoma Uniform Population

18 Metastatic Adenocarcinoma Masked Population PAX8

19 Cautionary Note Morphologic overlap between reactive mesothelial cells and carcinoma. 300 pleural & 300 peritoneal effusions total. False positive rate = 0.5% False negative rate = 31.5% 71 to 73% of false negatives due to sampling error 27 to 29% due to cytopathologist error MOTHERBY, H. et al (1999) Diagnostic Cytopathology, 20,

20 Practical Considerations A positive interpretation of malignancy in effusion cytology may lead to intensifying or withholding therapy.

21 Example Lung Cancer AJCC Cancer Staging Manual (2010), 7 th edition.

22 Practical Considerations A positive interpretation of malignancy in effusion cytology may lead to intensifying or withholding therapy. Be conservative with a malignant diagnosis.

23 Practical Considerations Ancillary tests can provide useful information. Comparison with prior and/or concurrent biopsies can be valuable. If the diagnosis is uncertain, ask for more fluid as malignant effusions usually re-accumulate.

24 General Algorithmic Workup of Effusions Atypical epithelioid cells present Mesothelial Uncertain Carcinoma Immunohistochemistry WT-1 BerEP4 Calretinin B72.3 CK5/6 mcea D2-40 MOC31

25 General Algorithmic Workup of Effusions Mesothelial Atypical epithelioid cells present Clinical/radiologic suspicion Large morular clusters/atypia Immunohistochemistry No Yes Reactive Mesothelioma

26 General Algorithmic Workup of Effusions Diagnosis Atypical epithelioid cells present Carcinoma Age, sex, serous cavity involved Previous history of cancer Immunohistochemistry

27

28 Diagnostic Challenges Recognizing a reactive effusion Distinguishing reactive from malignant mesothelial cells Distinguish mesothelioma from adenocarcinoma Recognizing features of P.D. squamous cell carcinoma and other mimickers in effusions

29 Points to remember Fluid accumulation occurs with disease Fluids can be exudate or transudate Bloody fluid is indicative of malignancy or pulmonary infarction Malignant effusion is not always bloody Hemosiderin laden macrophages are indicative of chronic RBCs leak

30 Quiescent mesothelium-1 Monolayer of flattened sheets with epithelial features Cells break off as single cells or in few groups Round to oval cells, µm in diameter Cytoplasm moderate in amount, translucent, with peripheral glycogen vacuoles Long slender microvilli appear as a pale zone at the periphery causing a fuzzy or brush like appearance by LM Central portion of cytoplasm is denser and darker due to perinuclear intermediate filaments causing endo-ectoplasmic demarcation

31 Quiescent mesothelium-2 Cells may be single or binucleated Nuclei are monotonous, centrally located, and oval to round, with evenly distributed chromatin Nucleoli are indistinct Occasional cells exhibit the characteristic window and cellular clasping appearance

32 1 Normal Mesothelium

33 Diagnostic Challenges Recognizing a reactive effusion Distinguishing reactive from malignant mesothelial cells Distinguish mesothelioma from adenocarcinoma Recognizing features of P.D. squamous cell carcinoma in effusions

34 Reactive/Hyperplasic Mesothelium Shed as doublets or triplets with windows between them Few papillary groups may be formed Connections by clasp-like articulations are more obvious Cells are round to oval, 20-40µm in diameter Abundant cytoplasm with endo-ectoplasmic demarcation and peripheral submembranous vacuoles Cytoplasmic protrusions distal to cellular connection

35 Mesothelial Cells

36 Mesothelial Cells

37 Reactive Mesothelium

38 Causes of Mesothelial Hyperplasia Heart failure Infection (pneumonia, lung abscess) Infarction (may shed in sheets) Liver disease such as hepatitis or cirrhosis Collagen disease Renal disease/peritoneal dialysis Pancreatic disease Radiation and chemotherapy Traumatic irritation (surgery) Chronic inflammation (PID, pleuritis) Underlying neoplasm causing irritation (fibroid) Foreign substance (talc, asbestos)

39 Radiation Therapy

40 Malignant Mesothelioma Why is it important to diagnose in fluids? 1. Different therapeutic implications 2. Spare the patient additional procedures with higher morbidity and risk of tumor seeding 3. Medicolegal compensation for asbestos exposure

41 Malignant Mesothelioma Fluids are generally highly cellular Could be scant in cellularity Key cytologic feature: larger cells with some attaining gigantic size

42 Malignant Mesothelioma Early stage: Hundreds of tiny nodules on the serosal membrane. Pleural thickening and plaques when associated with asbestos exposure Late stage: Nodules become confluent and serosal membrane becomes thickened and gradually the parietal and visceral pleura fuse and fluid disappears.

43 Malignant Mesothelioma Epithelial: tubulopapillary, W,D. papillary, epithelioid, transitional, deciduoid, clear, microcystic, small cell Sarcomatous Biphasic Anaplastic

44 Malignant Mesothelioma Arriving at Diagnosis First: Recognize mesothelial features Second: Recognize their malignant features

45 Malignant Mesothelioma How to Recognize It-1 Highly cellular smears All cells look alike, i.e. one cell population Cellular spheres with smooth borders (modules) Tight and loose clusters with scalloped borders High number of cells within clusters Cells vary in size and shape widely with some gigantic cells Large multinucleated cells approaching size of some morules Mesothelial cell features easily recognized/exaggerated

46 Malignant Mesothelioma How to Recognize It-2 Yellow glycogen is frequently detected Nuclei are usually bland or slightly atypical (nuclear irregularity, coarse chromatin, and hyperchromasia) Very prominent nucleoli Background of numerous lymphocytes or abundant blood Thick extracellular matrix (hyaluronic acid) causing the grossly recognized thick consistency described as Tarlike or Honey-like consistency.

47 Malignant Mesothelioma

48 Malignant Mesothelioma

49 Extracellular Matrix

50 W.D. Papillary Mesothelioma

51 Remember Not all fluids of mesothelioma are cellular Not all mesotheliomas associated with asbestos (1/3 of cases are not) Not all mesotheliomas contain morules, some present as single cells only Effusions are large, unilateral and recur fast and frequently A low cellularity on a repeated tap within a short interval does not exclude the diagnosis of mesothelioma

52 Differential Diagnosis: Papillary Clusters or Cell Balls Adenocarcinoma Breast Lung Ovary Prostate (rare) Florid mesothelial hyperplasia Malignant mesothelioma P.D. squamous and urothelial carcinoma

53 How To Approach The Diagnosis? 1. Is there one or two cell population? 2. Are the cells monotonous (look-alike) or pleomorphic (variable in shape and atypia)? 3. Is there a small size range or is there wide variation in size? 4. What cellular features you see? Two tone, vacuolated etc.. 5. Are the nuclei highly atypical or not?

54 Adenocarcinoma: Breast

55 Adenocarcinoma: Ovary

56 Squamous Cell Carcinoma

57 Markers of Mesothelium Calretinin Podoplanin and D2-40 Cytokeratin 5/6 WT-1 Mesothelin Thrombomodulin

58 Calretinin Mesothelioma 100% Lung ADC 6-10% Serous ADC 31-38% Squamous CC 40% Renal CC 0-10% Best to separate mesothelioma from lung ADC or renal Cannot separate mesothelioma from sqcc and serous ADC Negative stain argues against a mesothelioma

59 Podoplanin Mesothelioma % positive Membranous pattern along the apical surface Lung adenocarcinoma-negative Squamous cell carcinoma 30% positive Serous carcinoma 15% positive Expressed in epith. Component of syn. Sar and angiosarcoma Best to separate mesothelioma from lung ADC or renal Cannot separate mesothelioma from sqcc and serous ADC

60 Keratin 5 and 6 Epithelioid mesothelioma % Lung ADC 0-19%* Serous & breast carcinoma 22-35% Squamous ca Positive Renal cell ca 0% Best to separate mesothelioma from lung ADC or renal Cannot separate mesothelioma from sqcc and gynecologic ADC * Probably squamous differentiation

61 WT-1 Nuclear stain Epithelioid mesothelioma 43-93% Lung ADC 0%* Squamous CC of lung 0% Serous carcinoma % RCC rare *3/13 + in our series Useful to separate mesothelioma from lung ADC and squamous ca

62 Thrombomodulin (CD141) Membranous staining pattern (not cytoplasmic) Epith.mesothelioma (strong) % Lung ADC (focal) &EMs 5-77% RCC 0% Squamous CC Frequent Can be expressed in epithelioid hemangioendothelioma and angiosarcoma Limited use. Can separate mesothelioma from RCC

63 Mesothelin E. Mesothelioma (strong/cytop) 100% Lung ADC (focal/memb) 39% Squamous CC (focal/memb) 27% Pancreas ADC (strong) Ovarian and pancreatic Few RCC 0% Negative staining argues against mesothelioma

64 Epithelial/Carcinoma Markers Moc-31 Ber-EP4 B72.3 CEA Leu-M1 BG-8

65 MOC-31 Epithelial cell adhesion molecule Lung ADC % Lung Squamous CC 97%% Serous carcinoma 98% RCC 50% E. Mesothelioma 2-10% focal Best positive marker to distinguish ADC and squamous from mesothelioma

66 Ber-EP4 Epithelial cell adhesion molecule ADC % Lung ADC 100% Serous ca 100% Lung squamous 87% RCC 42% E. Mesothelioma 13% Can be useful in separating mesothelioma form ADC and SQCC

67 MM Vs ADC vs Sqcc Best positive markers for mesothelioma Calretinin, CK 5/6, WT-1, Podoplanin Best negative markers for mesothelioma Moc31, BerEP4, B72.3, CEA, BG-8 Best positive for Sqcc CK5/6, MOC31, Ber-EP4, CEA, BG-8, P63 Best negative for Sqcc WT-1

68 Reactive Mesothelium Vs Mesothelioma Antibody Reactive Malignant Mesothelium Mesothelioma EMA ---/+ +++/- Desmin +++/- ---/+ P53 ---/+ ++/-- Ki67 ---/+ ++/--

69 Unknown 1: Pleural Fluid 55 year old male with history of pneumonia

70 Features Favoring Reactive Mesothelium One cell population with monotonous appearance Atypia is not very pronounced Cellular clusters may be present but not as tight as spheres Little variation in size or shape of cells Classic features of mesothelium including cytoplasmic glycogen

71 25 Reactive Versus Malignant EMA Desmin

72 Unknown 2: Pleural Fluid 74 years old male with a 10 cm renal mass and ascites

73 Features Favoring Mesothelioma Monotonous population with mild to moderate atypia Morules and numerous discohesive cells Numerous multinucleated giant cells Markedly enlarged cells (5-10 times that of normal mesothelium) Background cells show a wide range of size Features indicative of mesothelial origin

74 Unknown 3: Peritoneal Fluid 66 years old female with possible adnexial mass

75 Unknown 3: Peritoneal Fluid 22

76 Features favoring Adenocarcinoma Pleomorphic population of cells with obvious atypia Little variation in size of cells Two cell population (background of reactive mesothelium) may be detected Lack of two tone cytoplasm Cytoplasmic glycogen rarely seen (lung adenoca) True gland formation may be seen in some clusters

77

78 Patterns of Metastatic Carcinomas in Effusions Acinar clusters unifying feature of adenocarcinomas of any origin.

79 Patterns of Metastatic Carcinomas in Effusions Acinar clusters unifying feature of adenocarcinomas of any origin. Spherules ( cannonballs ) Papillary/branching clusters Psammomatous calcifications Single cells Linear chains Signet ring cells

80 Spherules ( cannonballs ) Can be seen in adenocarcinomas arising from: Breast Lung Müllerian (endometrioid) Can also be seen in mesothelioma (and some cases of mesothelial hyperplasia).

81 * Breast cancer rarely presents as a malignant effusion. Spherules ( cannonballs ) Breast* Müllerian Lung Meso

82 Immunohistochemical Adjuncts - Summary Lung: TTF-1, Napsin A Breast: ER/PR, GCDFP-15, mammaglobin Müllerian: ER/PR, WT-1, PAX8 Mesothelioma: calretinin, D2-40, WT-1 Napsin A Mammaglobin PAX8

83 Papillary/Branching Clusters Müllerian (papillary serous adenocarcinoma) Lung Mesothelioma & mesothelial hyperplasia Colon Pancreaticobiliary

84 Papillary/Branching Clusters Lung Müllerian Meso

85 Papillary/Branching Clusters Colon Pancreas

86 Immunohistochemical Adjuncts - Summary Lung: TTF-1, Napsin A Müllerian: ER/PR, WT-1, PAX8 Mesothelioma: calretinin, D2-40, WT-1 Colon: CK20, CDX-2 Pancreas: Smad4 (loss of expression)

87 Psammomatous Calcifications Can be seen in association with papillary clusters in the following malignancies: Müllerian (papillary serous adenocarcinoma) Lung Mesothelioma & mesothelial hyperplasia Thyroid (papillary thyroid carcinoma)

88 Psammomatous Calcifications Müllerian (DQ) Müllerian (Pap)

89 Psammomatous Calcifications Lung adenocarcinoma

90 Dyscohesion/Single Cells Carcinoma Poorly differentiated adenocarcinoma Small cell carcinoma Breast (lobular carcinoma) Lymphoma Melanoma Renal cell carcinoma Hepatocellular carcinoma Sarcoma

91 Dyscohesion/Single Cells Carcinoma Poorly differentiated adenocarcinoma Small cell carcinoma Breast (lobular carcinoma) Lymphoma Melanoma Renal cell carcinoma Hepatocellular carcinoma Sarcoma

92 Poorly-differentiated Adenocarcinoma Breast Müllerian Gastric Pancreas Colon

93 Single Cells + Linear Chains Carcinoma Poorly differentiated carcinoma Small cell carcinoma Breast (lobular carcinoma) Melanoma Lymphoma Renal cell carcinoma Hepatocellular carcinoma Sarcoma

94 Small cell carcinoma

95 Ancillary Studies Small cell carcinoma Flow cytometry: CD56+/CD45(-) FARINOLA, M.A. et al (2003) Cancer Cytopathology, 99,

96 Ancillary Studies Small cell carcinoma Immunohistochemistry: CD56, chromogranin, synaptophysin, TTF-1 CD45 CD56

97 Lobular Carcinoma of the Breast

98 Lobular Carcinoma of the Breast

99 Signet Ring Cells Breast Gastric

100 Signet Ring Cells Mucicarmine PAS + Diastase

101 Immunohistochemical Adjuncts Breast: CK7, ER/PR, GCDFP-15, mammaglobin Gastric: CK7, CK20 (variable), CDX-2

102 Lobular Carcinoma of the Breast Estrogen Receptor

103 Immunohistochemical Adjuncts - Summary Lung (adenocarcinoma): TTF-1, Napsin A Lung (small cell CA): TTF-1, chromogranin, synaptophysin, CD56 Breast: ER/PR, GCDFP-15, mammaglobin Müllerian: ER/PR, WT-1, PAX8 Gastrointestinal: CDX-2 Lower GI tract: CDX-2, CK20 Pancreaticobiliary: Smad4 (lost)

104 UNCOMMON EPITHELIAL MALIGNANCIES

105 Uncommon Neoplasms Mesothelioma Mimickers Squamous cell carcinoma Urothelial carcinoma Others: Renal cell carcinoma Thyroid carcinoma

106 Squamous Cell Carcinoma

107 Features Favoring P.D. Squamous Cell Carcinoma Third type cells with cyanophilic cytoplasm appearing singly or in large tight clusters Characteristic cell features: Very dense and distinct cell border Dense periphery or hyaline in appearance indicate attempt to keratinize Refractile rings indicative of abnormal keratinization Endo-ectoplasmic demarcation (ectoplasm is dense while endoplasm is more textured) because keratinization starts at the periphery Endo-ectoplasmic border can be ruffled or thrown into linear folds keratinizing fibrils or Herxheimer s spirals Small clusters of cells arranged in whorls as they rap around each other recapitulating keratin pearl Cells appearing as doublets or short cords (cell junctions)

108 Squamous Cell Carcinoma

109 Squamous Versus Mesothelium Squamous Cell Carcinoma Malignant Mesothelioma

110 Squamous Versus Mesothelium Squamous Carcinoma Mesothelioma

111 Squamous Cell Carcinoma

112 Cell Junction Versus Window Junction Junction Window

113 Keratin Pearl

114 Urothelial Carcinoma Clusters and single cells Windows, junctions, cells within cells and claspinglike features Cercariform cells Large nuclei with open and regularly distributed chromatin Moderately enlarged nucleoli Multiple nucleoli Rounded nuclear borders

115 Urothelial Carcinoma

116

117 UCC: IHC Negative for mesothelial markers Positive to CK7 &CK20 and may react to CK5/6 CK-7 CK-20 CK5/6

118 Thyroid Carcinoma Papillary thyroid most common Effusion is low in Cellularity Clusters and single cell Psammoma bodies not always present Intranuclear inclusions may not be present

119 Thyroid Carcinoma: Papillary

120 Thyroid Carcinoma: Papillary

121 Papillary Thyroid Thyroglobulin TTF-1

122

123 Case #1 68 y.o. female with cryptogenic cirrhosis and ascites. Physical exam reveals hepatosplenomegaly and fluid wave in the abdomen. No prior history of malignancy.

124 Case #1

125 Case #1 CD20 CD5 CD23

126 Case #1

127 Case #1

128 Case #1 Liver Bx

129 Case #1 Liver Bx CD20

130 Case #1 Liver Bx CD20 CD5

131 Case #1 Liver Bx CD20 CD5 CD23

132 Case #1 DIAGNOSIS: Small lymphocytic lymphoma (SLL)

133 Dyscohesion/Single Cells Carcinoma Poorly differentiated adenocarcinoma Small cell carcinoma Breast (especially lobular carcinoma) Lymphoma Melanoma Renal cell carcinoma Hepatocellular carcinoma Sarcoma

134 Lymphoma Effusions rich in lymphocytes raise the possibility of lymphoma but can be seen in reactive conditions (e.g., tuberculosis). Distinguishing a reactive lymphocytosis from a mature, small B-cell neoplasm can be morphologically difficult.

135 Lymphoma Practical Considerations It is very rare for non-hodgkin lymphoma to present as a malignant effusion; hence, if no history of lymphoma, not likely lymphoma. If there is a history of lymphoma, ancillary studies (e.g., flow cytometry & IHC) are useful. N.B. Beware of blood contamination (i.e., Bloody effusion? Peripheral blood count?)

136 Small B-cell Neoplasms CLL/SLL CD5+ Mantle Cell

137 Small B-cell Neoplasms CLL/SLL CD23+ Cyclin D1(-) CD5+ Mantle Cell CD23(-) Cyclin D1+

138 Small B-cell Neoplasms CLL/SLL CD23+ Cyclin D1(-) CD5+ Mantle Cell CD23(-) Cyclin D1+ Follicular CD5(-) Marginal Zone

139 Small B-cell Neoplasms CLL/SLL CD23+ Cyclin D1(-) CD5+ Mantle Cell CD23(-) Cyclin D1+ Follicular CD10(+/-) CD5(-) Marginal Zone CD10(-)

140 Small B-cell Neoplasms CLL/SLL CD23+ Cyclin D1(-) CD5+ Mantle Cell CD23(-) Cyclin D1+ t(11:14) (q13;q32) Follicular CD10(+/-) t(14:18) (q32;q21) CD5(-) Marginal Zone CD10(-) t(11:18) (q21;q21)

141 Case #2 55 y.o. female with a history of non-hodgkin lymphoma s/p BMT presents with dyspnea. Imaging reveals the presence of a large unilateral (right) pleural effusion.

142 Case #2

143 Case #2 CD20 Cyclin D1

144 Case #2

145 Case #2

146 Case #2 DIAGNOSIS: Mantle cell lymphoma.

147 Mantle Cell Lymphoma - FISH

148 Mantle Cell Lymphoma - FISH Evidence of t(11:14) translocation LI, J. Y. et al (1999) American Journal of Pathology, 154,

149 Case #3 85 year old man with a history of non-hodgkin lymphoma s/p chemotherapy presents with worsening cough and dyspnea on exertion. Prior history of tuberculosis. Imaging detects a left sided pleural effusion.

150 Case #3

151 Case #3

152 Follicular Lymphoma - FISH Evidence of t(14:18) translocation

153 Case #3 DIAGNOSIS: Follicular lymphoma.

154 Case #4 23 y.o. man presents with diffuse abdominal pain. Imaging reveals a 4.5 cm mass posterior to the pancreas, omental thickening, and marked ascites.

155 Case #4

156 Case #4 CD20

157 Case #4 Omental Bx CD20 BCL6 Ki67/Mib-1

158 Case #4

159 Case #4 DIAGNOSIS: Non-Hodgkin lymphoma, large B-cell type. (Burkitt s lymphoma).

160 Large Cell Lymphoma Large lymphocytes are not often amenable to analysis by flow cytometry. Fortunately, the large lymphocytes often appear obviously malignant cytologically. The most common large cell lymphoma in effusions is DLBCL. Immunostains for LCA, CD3, and CD20 are usually sufficient.

161 Primary Effusion Lymphoma

162 Case #5 78 y.o. man presents with a left lower lobe lung mass associated with a left pleural effusion. Past medical history is significant for a remote history of melanoma of the back and forehead.

163 Case #5

164 Case #5 HMB45

165 Case #5 DIAGNOSIS: Positive for malignant cells. Consistent with metastasis from the patient s melanoma.

166 Case #6 25 y.o. male presents with dyspnea. Past surgical history is remarkable for a sarcoma resection from the right proximal sartorius muscle. Imaging reveals hilar lymphadenopathy, multiple lung and pleural nodules and bilateral pleural effusions (right > left).

167 Case #6

168 Case #6 Myogenin

169 Case #6 DIAGNOSIS: Positive for malignant cells. Consistent with metastasis from the patient s high-grade, pleomorphic rhabdomyosarcoma.

170 Case #7 21 y.o. female presents with dyspnea and left upper quadrant pain. Past surgical history is significant for a sarcoma resection from the right fibula. Imaging reveals multiple lung and pleural nodules along with a new left pleural effusion.

171 Case #7

172 Case #7

173 Case #7 Calretinin

174 Case #7 Calretinin CD99

175 Case #7 DIAGNOSIS: Positive for malignant cells. Consistent with metastasis from the patient s Ewing s sarcoma.

176 Sarcoma Practical Considerations Any sarcoma can metastasize to serosal surfaces. Nonetheless, as a whole, sarcomas represent an uncommon cause of malignant effusions. Malignant effusions secondary to metastatic sarcoma is usually encountered late in the course of the disease (i.e., patients already carry a sarcoma diagnosis).

177 THANK YOU Stewart Knoepp, M.D., Ph.D. Xin Jing, M.D. Robertson Davenport, M.D. Rodolfo Rasche, M.D. Cohra Mankey, M.D. Bryan Betz, Ph.D.

178 ASC Workshop 3-Effusion Cytology: Charting a course through and navigating the waters Claire W. Michael, MD Michael H. Roh, MD, PhD University of Michigan Medical School REFERENCES Epithelial Neoplasms ASHTON, P. R., HOLLINGSWORTH, A. S. & JOHNSTON, W. W. (1975) Cytopathology of Metastatic Breast-Cancer. Acta Cytologica, 19, 1-6. BEDROSSIAN, C. W. M. (1994) Malignant effusions : a multimodal approach to cytologic diagnosis, New York, Igaku-Shoin. CHHIENG, D. C., KO, E. C., YEE, H. T., SHULTZ, J. J., DORVAULT, C. C. & ELTOUM, I. A. (2001) Malignant pleural effusions due to small-cell lung carcinoma: A cytologic and immunocytochemical study. Diagnostic Cytopathology, 25, DANNER, D. E. & GMELICH, J. T. (1975) Comparative Study of Tumor-Cells from Metastatic Carcinoma of Breast in Effusions. Acta Cytologica, 19, DELAHAYE, M., VAN DER HAM, F. & VAN DER KWAST, T. H. (1997) Complementary value of five carcinoma markers for the diagnosis of malignant mesothelioma, adenocarcinoma metastasis, and reactive mesothelium in serous effusions. Diagnostic Cytopathology, 17, DIBONITO, L., FALCONIERI, G., COLAUTTI, I., BONIFACIO, D. & DUDINE, S. (1992) The Positive Pleural Effusion - a Retrospective Study of Cytopathologic Diagnoses with Autopsy Confirmation. Acta Cytologica, 36, DIBONITO, L., FALCONIERI, G., COLAUTTI, I., BONIFACIO, D. & DUDINE, S. (1993) The Positive Peritoneal Effusion - a Retrospective Study of Cytopathologic Diagnoses with Autopsy Confirmation. Acta Cytologica, 37, FANNING, J., MARKULY, S. N., HINDMAN, T. L., GALLE, P. C., MCRAE, M. A., VISNESKY, P. M. & HILGERS, R. D. (1996) False positive malignant peritoneal cytology and psammoma bodies in benign gynecologic disease. Journal of Reproductive Medicine, 41, FARINOLA, M. A., WEIR, E. G. & ALI, S. Z. (2003) CD56 expression of neuroendocrine neoplasms on immunophenotyping by flow cytometry - A novel diagnostic approach to fine-needle aspiration biopsy. Cancer Cytopathology, 99,

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