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Cerebrospinal Fluid (CSF) Findings in Post-Transplant Lymphoproliferative Disorder (PTLD)
Journal of the American Society of Cytopathology (2012) 1, S17eS23
Available online at www.sciencedirect.com
FLUIDS/CSF
11
10
Cerebrospinal Fluid (CSF) Findings in Post-Transplant Lymphoproliferative Disorder (PTLD)
Thyroid Transcription Factor-1 (TTF-1) and Napsin A Double Staining in Metastatic Adenocarcinoma in Pleural Fluid Lian Liu, MD, PhD, Cynthia Cohen, MD, Momin Siddiqui, MD, FIAC. Pathology, Emory University, Atlanta, Georgia Introduction: Thyroid transcription factor-1 (TTF-1)/Napsin A double staining has been found useful for identification of primary lung adenocarcinoma. In the current study, we examined the performance of TTF-1/ Napsin A double stain in identification of metastatic lung adenocarcinoma in pleural fluid. Materials and Methods: 38 pleural fluid specimens collected between 2008 and 2011 diagnosed with metastatic adenocarcinoma were identified. Among these, 23 cases were diagnosed with a lung primary, and 15 with a non-lung primary [breast (nZ13), ovarian (nZ1) and esophageal (nZ1)]. Immunohistochemistry was performed on formalin-fixed, paraffinembedded cell blocks. Expression of TTF-1 as brown nuclear stain and Napsin A as red cytoplasmic stain were identified as positive staining. Results: Among the cases with metastatic lung adenocarcinoma, 19/23 (83%) cases were positive for the TTF-1/ Napsin A double stain; 1/23 (4%) was positive for TTF-1 only; 2/23 (9%) were positive for Napsin A only; and 1/23 (4%) was negative for the TTF-1/ Napsin A double stain. All 15 cases of non-lung primary adenocarcinoma were negative for the TTF-1/ Napsin A double stain. Among the four cases of metastatic lung adenocarcinoma, which either stained with only TTF-1 (nZ1), Napsin A (nZ2), or were negative for both (nZ1), three of them were shown to be poorly differentiated adenocarcinoma in lung or pleural biopsy specimens.
Lung Primary Non-lung Primary
TTF-1/ Napsin A double stain TTF-1 Napsin A
TTF-1 / Napsin A Double Stain
TTF-1 Alone
Napsin A Alone
Double Negative
19/23 (83%) 0/15 (0%)
1/23 (4%) 0/15 (0%)
2/23 (9%) 0/15 (0%)
1/23 (4%) 15/15 (100%)
Sensitivity
Specificity
Positive Predictive Value (PPV)
Negative Predictive Value (NPV)
83%
100%
100%
79%
87% 91%
100% 100%
100% 100%
83% 88%
Conclusions: In conclusion, TTF-1/ Napsin A double stain is useful in identifying metastatic lung adenocarcinoma in pleural fluid. The sensitivity of Napsin A for metastatic lung adenocarcinoma is slightly higher than TTF-1, even though not statistically significant in our study. The sensitivity of both TTF-1 and Napsin A is lower in poorly differentiated lung adenocarcinoma. Lastly, TTF-1/ Napsin A double stain is highly specific for diagnosing metastatic lung adenocarcinoma, compared with nonpulmonary, in pleural fluid. 2213-2945/$ Ó 2012 American Society of Cytopathology.
Sarah Gibson, MD, Sara Monaco, MD, Walid Khalbuss, MD, PhD, Jennifer Picarsic, MD, Liron Pantanowitz, MD. Pathology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania Introduction: Post-transplant lymphoproliferative disorder (PTLD) is a potentially fatal condition that may occur in solid organ and allogeneic hematopoietic stem cell transplant recipients. It is important to establish a diagnosis of PTLD in cerebrospinal fluid (CSF) because of its associated poor prognosis. However, CSF findings of PTLD are not well described. Our aim was to therefore investigate the CSF findings in a series of patients with PTLD. Materials and Methods: A 24-year retrospective review was conducted for all cases with PTLD and cytology specimens in our computer system. Cases with CSF samples were further analyzed recording patient demographics, transplant history, cytologic findings, PTLD subtype, ancillary studies including EBV status and clinical follow up. Results: Of 103 total patients with PTLD, 25 (24%) had CSF cytology samples (94 specimens). CSF diagnoses ranged from negative (nZ73) to atypical (nZ12), suspicious (nZ3) and positive (nZ4) for PTLD. The 6 (24%) patients (7 specimens) with suspicious/positive CSF all had previously or concurrently diagnosed PTLD (4 monomorphic, 2 polymorphic). Autopsy in 2 cases confirmed PTLD involving brain tissue. These 6 patients (3 males, 3 females) were of average age 40 years (range, 9-63) with solid organ (2 liver, 2 kidney, 1 bilateral lung) or allogeneic peripheral blood stem cell transplantation 1 to 9 years preceding their CSF diagnoses. Flow cytometry was performed in 2 cases and was positive in 1 monomorphic PTLD, but negative in 1 polymorphic PTLD. EBV was positive in 1 of 3 cases with sufficient material for PCR studies. Conclusions: Approximately 20% of CSF samples from patients with PTLD contained atypical lymphoid cells. In CSF specimens from patients with a history of solid organ or allogeneic hematopoietic stem cell transplantation, an atypical polymorphous lymphoid population should raise suspicion for involvement by PTLD, despite negative flow cytometry findings. Clinical history and triage of CSF for EBV identification may help distinguish these cases from a reactive lymphocytosis. 12 The Clinical Utility of Peritoneal Washings in Gynecologic Surgery and Potential Cost Savings with Elimination of Unnecessary Specimen Processing Oliver Szeto, MD, Alexander Finkelstein, MD, Fang Zhou, MD, Aylin Simsir, MD. Pathology, NYU Langone Medical Center, New York, New York Introduction: Peritoneal washings (PW) are collected during abdominal surgery for presumed benign disease as well as malignant or suspected gynecologic neoplasms. Malignant cells in PW from ovarian neoplasms, in
Available online at www.sciencedirect.com
FLUIDS/CSF
11
10
Cerebrospinal Fluid (CSF) Findings in Post-Transplant Lymphoproliferative Disorder (PTLD)
Thyroid Transcription Factor-1 (TTF-1) and Napsin A Double Staining in Metastatic Adenocarcinoma in Pleural Fluid Lian Liu, MD, PhD, Cynthia Cohen, MD, Momin Siddiqui, MD, FIAC. Pathology, Emory University, Atlanta, Georgia Introduction: Thyroid transcription factor-1 (TTF-1)/Napsin A double staining has been found useful for identification of primary lung adenocarcinoma. In the current study, we examined the performance of TTF-1/ Napsin A double stain in identification of metastatic lung adenocarcinoma in pleural fluid. Materials and Methods: 38 pleural fluid specimens collected between 2008 and 2011 diagnosed with metastatic adenocarcinoma were identified. Among these, 23 cases were diagnosed with a lung primary, and 15 with a non-lung primary [breast (nZ13), ovarian (nZ1) and esophageal (nZ1)]. Immunohistochemistry was performed on formalin-fixed, paraffinembedded cell blocks. Expression of TTF-1 as brown nuclear stain and Napsin A as red cytoplasmic stain were identified as positive staining. Results: Among the cases with metastatic lung adenocarcinoma, 19/23 (83%) cases were positive for the TTF-1/ Napsin A double stain; 1/23 (4%) was positive for TTF-1 only; 2/23 (9%) were positive for Napsin A only; and 1/23 (4%) was negative for the TTF-1/ Napsin A double stain. All 15 cases of non-lung primary adenocarcinoma were negative for the TTF-1/ Napsin A double stain. Among the four cases of metastatic lung adenocarcinoma, which either stained with only TTF-1 (nZ1), Napsin A (nZ2), or were negative for both (nZ1), three of them were shown to be poorly differentiated adenocarcinoma in lung or pleural biopsy specimens.
Lung Primary Non-lung Primary
TTF-1/ Napsin A double stain TTF-1 Napsin A
TTF-1 / Napsin A Double Stain
TTF-1 Alone
Napsin A Alone
Double Negative
19/23 (83%) 0/15 (0%)
1/23 (4%) 0/15 (0%)
2/23 (9%) 0/15 (0%)
1/23 (4%) 15/15 (100%)
Sensitivity
Specificity
Positive Predictive Value (PPV)
Negative Predictive Value (NPV)
83%
100%
100%
79%
87% 91%
100% 100%
100% 100%
83% 88%
Conclusions: In conclusion, TTF-1/ Napsin A double stain is useful in identifying metastatic lung adenocarcinoma in pleural fluid. The sensitivity of Napsin A for metastatic lung adenocarcinoma is slightly higher than TTF-1, even though not statistically significant in our study. The sensitivity of both TTF-1 and Napsin A is lower in poorly differentiated lung adenocarcinoma. Lastly, TTF-1/ Napsin A double stain is highly specific for diagnosing metastatic lung adenocarcinoma, compared with nonpulmonary, in pleural fluid. 2213-2945/$ Ó 2012 American Society of Cytopathology.
Sarah Gibson, MD, Sara Monaco, MD, Walid Khalbuss, MD, PhD, Jennifer Picarsic, MD, Liron Pantanowitz, MD. Pathology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania Introduction: Post-transplant lymphoproliferative disorder (PTLD) is a potentially fatal condition that may occur in solid organ and allogeneic hematopoietic stem cell transplant recipients. It is important to establish a diagnosis of PTLD in cerebrospinal fluid (CSF) because of its associated poor prognosis. However, CSF findings of PTLD are not well described. Our aim was to therefore investigate the CSF findings in a series of patients with PTLD. Materials and Methods: A 24-year retrospective review was conducted for all cases with PTLD and cytology specimens in our computer system. Cases with CSF samples were further analyzed recording patient demographics, transplant history, cytologic findings, PTLD subtype, ancillary studies including EBV status and clinical follow up. Results: Of 103 total patients with PTLD, 25 (24%) had CSF cytology samples (94 specimens). CSF diagnoses ranged from negative (nZ73) to atypical (nZ12), suspicious (nZ3) and positive (nZ4) for PTLD. The 6 (24%) patients (7 specimens) with suspicious/positive CSF all had previously or concurrently diagnosed PTLD (4 monomorphic, 2 polymorphic). Autopsy in 2 cases confirmed PTLD involving brain tissue. These 6 patients (3 males, 3 females) were of average age 40 years (range, 9-63) with solid organ (2 liver, 2 kidney, 1 bilateral lung) or allogeneic peripheral blood stem cell transplantation 1 to 9 years preceding their CSF diagnoses. Flow cytometry was performed in 2 cases and was positive in 1 monomorphic PTLD, but negative in 1 polymorphic PTLD. EBV was positive in 1 of 3 cases with sufficient material for PCR studies. Conclusions: Approximately 20% of CSF samples from patients with PTLD contained atypical lymphoid cells. In CSF specimens from patients with a history of solid organ or allogeneic hematopoietic stem cell transplantation, an atypical polymorphous lymphoid population should raise suspicion for involvement by PTLD, despite negative flow cytometry findings. Clinical history and triage of CSF for EBV identification may help distinguish these cases from a reactive lymphocytosis. 12 The Clinical Utility of Peritoneal Washings in Gynecologic Surgery and Potential Cost Savings with Elimination of Unnecessary Specimen Processing Oliver Szeto, MD, Alexander Finkelstein, MD, Fang Zhou, MD, Aylin Simsir, MD. Pathology, NYU Langone Medical Center, New York, New York Introduction: Peritoneal washings (PW) are collected during abdominal surgery for presumed benign disease as well as malignant or suspected gynecologic neoplasms. Malignant cells in PW from ovarian neoplasms, in