SPECIAL CONTRIBUTION: DIAGNOSTIC DILEMMA Section Editor: Claire W. Michael, MD
Cytodiagnostic Aspects of Lung Adenocarcinoma Manifesting With Micropapillary Pattern in Sputum: A Case Report of Potential Diagnostic Pitfall Nien-Yi Chang, M.D.,1,2* John Wang, M.D., and Su-Wey Chen, C.T.1
3 Ph.D.,
Cheng-Ching Lin, M.D.,1
The micropapillary pattern of lung adenocarcinoma was discussed in the 2004 World Health Organization classification and is now proposed as a distinct pattern in the new International Multidisciplinary Classification of Lung Adenocarcinoma Guidelines. The micropapillary pattern is histologically characterized by papillary tufts lacking a central fibrovascular core and is associated with an unfavorable prognosis. Herein, we report the cytological features of lung adenocarcinoma with the micropapillary pattern in a sputum specimen. A 75-year-old woman presented with a productive cough, blood-tinged sputum, and some symptoms of upper respiratory tract infection. The initial impressions from her chest radiograph and computed tomography scan indicated pneumonia. However, the initial sputum cytology sample showed a few clusters of cells with abnormal three-dimensional structure, interpreted as adenocarcinoma. These cells were small and had minimal cytologic atypia, demonstrating a potential diagnostic pitfall. The following biopsy confirmed lung adenocarcinoma with the micropapillary pattern. Here, we describe this case and discuss the differential diagno-
1 Department of Anatomic Pathology, Buddhist Dalin Tzu Chi General Hospital, Chiayi, Taiwan 2 Department of Pathology, Da Chien General Hospital, Miaoli, Taiwan 3 Department of Pathology, Taichung Veterans General Hospital, Tachiung, Taiwan *Correspondence to: Nien-Yi Chang, M.D., Department of Pathology, Da Chien General Hospital, Miaoli, Taiwan. E-mail: [email protected] Received 30 April 2013; Revised 20 November 2013; Accepted 9 January 2014 DOI: 10.1002/dc.23104 Published online 19 February 2014 in Wiley Online Library (wileyonlinelibrary.com).
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Diagnostic Cytopathology, Vol. 42, No 10
sis of pulmonary entities exhibiting similar morphologies. Diagn. Cytopathol. 2014;42:902–905. VC 2014 Wiley Periodicals, Inc. Key Words: sputum
lung adenocarcinoma; micropapillary; cytology;
Sputum cytology is regarded as a simple, inexpensive, and noninvasive test, although its diagnostic sensitivity is low, compared with bronchial brushing.1 In 2011, a new adenocarcinoma classification called the International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society (IASLC/ATS/ERS) International Multidisciplinary Lung Adenocarcinoma Classification2 was published. Most lung cancers are not resectable because of advanced disease stage, and a diagnosis is usually established on the basis of small biopsy specimens and cytology. Therefore, this new classification is relevant to resection specimens, small biopsy specimens, and cytology specimens. Compared with the 2004 World Health Organization classification,3 the IASLC/ATS/ERS committee proposed two new patterns and recommended describing identifiable patterns of adenocarcinoma in small biopsy and cytology specimens. The micropapillary pattern is one of the new patterns and its presence is associated with a poor prognosis. We present a case of lung adenocarcinoma manifesting with the micropapillary pattern on cytology of a sputum sample, which could be a potential diagnostic pitfall that requires differential diagnosis with similar pulmonary entities. C 2014 WILEY PERIODICALS, INC. V
Diagnostic Cytopathology DOI 10.1002/dc
LUNG ADENOCARCINOMA WITH MICROPAPILLARY PATTERN
Fig. 1. A: A few clusters of small-sized cells with three-dimensional structure and overlapping nuclei. Occasionally, isolated atypical cells are present (Papanicolaou stain, sputum, 3400). B: High-magnification view showing a ball-like cluster of tumor cells exhibiting a radiating flower-petal pattern, without a fibrovascular core. The nuclei were small with a high nuclear-cytoplasmic ratio, irregular nuclear outlines, and uneven chromatin distribution (Papanicolaou stain, sputum, 31000; inset, Liu’s stain, bronchial washing, 31000). C: Microcalcification resembling a psammoma body (Papanicolaou stain, sputum, 3400). D: Micropapillary tufts floating within alveolar spaces (hematoxylin–eosin stain, bronchial biopsy, 3400; inset, positive nuclear staining for thyroid transcription factor-1 in the micropapillary component). [Color figure can be viewed in the online issue, which is available at wileyonlinelibrary.com.]
Case Report Clinical History A 75-year-old woman without a prior history of malignancy was referred to our hospital. She presented with a productive cough, blood-tinged sputum, and some symptoms of upper respiratory tract infection. Chest radiography and computed tomography showed consolidation and ground-glass opacities with an air bronchogram in the right lower lung. No obvious mass lesion was noted, giving an initial impression of pneumonia. However, sputum cytology revealed adenocarcinoma. The following biopsy confirmed the presence of adenocarcinoma with the micropapillary pattern.
Cytological and Histological Findings On sputum cytology, only a few clusters of cells with three-dimensional structure and overlapping nuclei were
observed. Occasionally, isolated single atypical cells were also observed (Fig. 1A). At high magnification, the balllike cell cluster exhibited a radiating flower-petal pattern, without fibrovascular cores. The cells were small, displayed a high nuclear-cytoplasmic ratio and scant vacuolated cytoplasm, without intercellular molding. The nuclei demonstrated irregular outlines with uneven chromatin distribution and inconspicuous nucleoli (Fig. 1B). Microcalcifications, resembling psammoma bodies, were also recognized (Fig. 1C). In the bronchial biopsy specimen, small papillary clusters of glandular cells were observed within the alveolar airspace, which did not show fibrovascular cores (Fig. 1D). The tumor cells were small and cuboidal, with minimal nuclear atypia. The tumor nuclei in the biopsy specimen showed positive immunostaining for thyroid transcription factor-1 (Fig. 1D, inset). Further molecular analysis of the tumor revealed a deletion in exon 19 of the epidermal growth factor receptor gene. Diagnostic Cytopathology, Vol. 42, No 10
903
Diagnostic Cytopathology DOI 10.1002/dc
CHANG ET AL.
Fig. 2. A: Reserve cells under the surface columnar epithelium (ciliated bronchial cells) of the respiratory tract (hematoxylin–eosin stain, 3400). B and C: Reserve cells showing small, uniform, tightly cohesive, hyperchromatic cells with scant cytoplasm and smudged, dark, evenly distributed chromatin. Ciliated bronchial cells are seen around the reserve cells (Liu’s stain, B, 3400; C, 31000). [Color figure can be viewed in the online issue, which is available at wileyonlinelibrary.com.]
Discussion Lung cancer is the leading cause of cancer death, worldwide,4 with pulmonary adenocarcinoma being the most common histological type of primary lung carcinoma.3 Adenocarcinomas with predominantly solid or micropapillary patterns have significantly poorer prognoses than other types of lung cancers.5–9 The presence of a micropapillary component is associated with a significantly higher incidence of lymph node metastasis, pleural invasion, lymphatic invasion, and venous invasion.10 This pattern of lung adenocarcinoma was first reported by Amin et al.11 in 2002 and is characterized by small papillary tufts that lack fibrovascular cores, which may be detached and/or connected to the alveolar walls. The tumor cells are usually small and cuboidal with minimal nuclear atypia; psammoma bodies may be seen.2 Although cytologic criteria for the different subtypes of lung adenocarcinoma in different cytologic preparations have yet to be established, some unusual features were demonstrated in the sputum cytology of this patient. The tumor cells in this case were small and cuboidal, with nuclei that were 1–2 times the size of small lymphocytes without macronucleoli. The ball-like cell clusters exhibited a radiating flower-petal pattern without fibrovascular cores, and with fewer than 50 cells in each cell cluster. The tumor cells did not demonstrate glandular structures with central lumens or cohesive cell clusters in a sheet-like pattern, but psammoma body-like microcalcifications were evident. Although possibly nonspecific, these are easily observed in tumors with micropapillary features, e.g., papillary serous adenocarcinoma of the ovary. The most important differential diagnosis was reserve cell hyperplasia. Reserve cells are immature cells present under the surface columnar epithelium (ciliated bronchial 904
Diagnostic Cytopathology, Vol. 42, No 10
cells) of the respiratory tract (Fig. 2A). Reserve cells proliferate when the surface epithelium is shed during chronic irritation or lung injury. Cytomorphologically, reserve cell hyperplasia appears as small, uniform, tightly cohesive, hyperchromatic cells with scant cytoplasm and smudged, dark, evenly distributed chromatin; single cells are not seen (Fig. 2B). A few ciliated bronchial cells may be observed around the reserve cells (Fig. 2C). These cell clusters lack three-dimensional structure, nuclear molding, and evidence of mitosis or necrosis. Other differential diagnoses should include pulmonary entities that exhibit similar morphology, such as small cell carcinoma and carcinoid tumor.12 Some useful cytological features for the differential diagnosis of similar lesions are summarized in Table I. Does the cytological micropapillary pattern correlate with the histological subtyping? Rudomina et al.13 compared specific histological types of lung adenocarcinoma with their cytological patterns in fine-needle aspirations and identified micropapillary tufts in 48% of the histologically micropapillary pattern-negative group. Therefore, the detection of micropapillary tufts by fine-needle aspiration cytology does not provide a reliable correlation with the histological micropapillary component. The cytological preparation from an aspirated sample is often three dimensional, as it usually contains structured fragments of tissues that were removed in toto from their setting.14 Thus, the micropapillary tufts observed in fine-needle aspiration cytology are possibly the result of the negative pressure manipulations of the needle, not necessarily representing the histological micropapillary component. Sputum cytology, on the other hand, involves exfoliated material. Because the micropapillary component often floats within the alveolar spaces, it can spread aerogenously.10,15 As this case suggests, the micropapillary tufts in sputum cytology may correlate better with the
Diagnostic Cytopathology DOI 10.1002/dc
LUNG ADENOCARCINOMA WITH MICROPAPILLARY PATTERN Table I. Cytological Features of Pulmonary Entities Exhibiting Similar Morphology Adenocarcinoma with micropapillary pattern
Reserve cell hyperplasia
Focal necrotic Three-dimensional clusters, single cells, nuclear overlapping Scant, vacuolated Small, occasional mitosis Irregular Hyperchromatic, unevenly distributed/ occasional nucleoli Variable
Non-necrotic Cohesive clusters, no single cell, surrounding ciliated cells Scant, indistinct Small, rare mitosis Smooth Hyperchromatic, evenly distributed/indistinct nucleoli Rare
Cytological features Background Pattern Cytoplasm Nuclei Nuclear membrane Chromatin/nucleoli Incidence in sputum
histological micropapillary component. However, because this report represents a single case, the value of this apparent association will require the study of more cases for validation. In summary, although the diagnostic sensitivity of sputum samples is low, the micropapillary pattern, indicative of a poor prognosis, may be evident in these samples. The cytopathologist should be aware of the cytological features of adenocarcinoma manifesting with the micropapillary pattern in sputum and, when present, alert the clinician to perform further examinations to avoid delayed diagnosis and treatment.
Acknowledgments The authors thank the Department of Pathology of Taichung Veterans General Hospital, especially Professor Dr. John Wang, for their assistance in diagnosis.
References 1. Bedrossian CW, Rybka DL. Bronchial brushing during fiberoptic bronchoscopy for the cytodiagnosis of lung cancer: Comparison with sputum and bronchial washings. Acta Cytol 1976;20:446–453. 2. Travis WD, Brambilla E, Noguchi M, et al. International association for the study of lung cancer/American thoracic society/European respiratory society international multidisciplinary classification of lung adenocarcinoma. J Thorac Oncol 2011;6:244–285. 3. Travis WD, Brambilla E, Muller-Hermelink HK, Harris CC, editors. WHO Classification of tumors. Pathology and genetics of tumours of the lung, pleura, thymus and heart. Lyon: IARC Press; 2004. p 35–44. 4. Hoffman PC, Mauer AM, Vokes EE. Lung cancer. Lancet 2000; 355:479–485. 5. Russell PA, Wainer Z, Wright GM, Daniels M, Conron M, Williams RA. Does lung adenocarcinoma subtype predict patient survival? A clinicopathologic study based on the new International Association for the Study of Lung Cancer/American Thoracic Soci-
Small cell carcinoma
Carcinoid tumor
Necrotic Loose cluster, Indian-file arrangement, nuclear molding Scant, easily stripped Small, Brisk mitosis Smooth Granular, evenly distributed/ indistinct nucleoli
Non-necrotic Loose clusters, dispersive single cells, no nuclear molding Moderate, often stripped Small, rare mitosis Smooth Granular, stippled, “salt and pepper”/distinct small nucleoli Rare
Common
ety/European Respiratory Society international multidisciplinary lung adenocarcinoma classification. J Thorac Oncol 2011;6:1496– 1504. 6. Yoshizawa A, Motoi N, Riely GJ, et al. Impact of proposed IASLC/ATS/ERS classification of lung adenocarcinoma: Prognostic subgroups and implications for further revision of staging based on analysis of 514 stage I cases. Mod Pathol 2011;24:653–664. 7. Warth A, Muley T, Meister M, et al. The novel histologic international association for the study of lung cancer/American thoracic society/European respiratory society classification system of lung adenocarcinoma is a stage-independent predictor of survival. J Clin Oncol 2012;30:1438–1446. 8. Woo T, Okudela K, Mitsui H, et al. Prognostic value of the IASLC/ATS/ERS classification of lung adenocarcinoma in stage I disease of Japanese cases. Pathol Int 2012;62:785–791. 9. Gu J, Lu C, Guo J, et al. Prognostic significance of the IASLC/ ATS/ERS classification in Chinese patients-A single institution retrospective study of 292 lung adenocarcinoma. J Surg Oncol 2013; 107:474–480. 10. Zhang J, Liang Z, Gao J, Luo Y, Liu T. Pulmonary adenocarcinoma with a micropapillary pattern: A clinicopathological, immunophenotypic and molecular analysis. Histopathology 2011;59: 1204–1214. 11. Amin MB, Tamboli P, Merchant SH, et al. Micropapillary component in lung adenocarcinoma: A distinctive histologic feature with possible prognostic significance. Am J Surg Pathol 2002;26:358– 364. 12. Idowu MO, Powers CN. Lung cancer cytology: Potential pitfalls and mimics—A review. Int J Clin Exp Pathol 2010;3:367–385. 13. Rudomina DE, Lin O, Moreira AL. Cytologic diagnosis of pulmonary adenocarcinoma with micropapillary pattern: Does it correlate with the histologic findings? Diagn Cytopathol 2009;37:333–339. 14. Koss LG, Melamed MR. Koss’ diagnostic cytology and its histopathologic bases. 5th ed. Vol. 2. Philadelphia: Lippincott Williams & Wilkins; 2006. p 1056–1080. 15. Prior JO, Stupp R, Christodoulou M, Letovanec I. Micropapillary pattern in lung adenocarcinoma: Aspect on 18F-fluorodeoxyglucose positron emission tomography/computed tomography imaging. Interact Cardiovasc Thorac Surg 2010;10:144–145.
Diagnostic Cytopathology, Vol. 42, No 10
905
Cytodiagnostic Aspects of Lung Adenocarcinoma Manifesting With Micropapillary Pattern in Sputum: A Case Report of Potential Diagnostic Pitfall Nien-Yi Chang, M.D.,1,2* John Wang, M.D., and Su-Wey Chen, C.T.1
3 Ph.D.,
Cheng-Ching Lin, M.D.,1
The micropapillary pattern of lung adenocarcinoma was discussed in the 2004 World Health Organization classification and is now proposed as a distinct pattern in the new International Multidisciplinary Classification of Lung Adenocarcinoma Guidelines. The micropapillary pattern is histologically characterized by papillary tufts lacking a central fibrovascular core and is associated with an unfavorable prognosis. Herein, we report the cytological features of lung adenocarcinoma with the micropapillary pattern in a sputum specimen. A 75-year-old woman presented with a productive cough, blood-tinged sputum, and some symptoms of upper respiratory tract infection. The initial impressions from her chest radiograph and computed tomography scan indicated pneumonia. However, the initial sputum cytology sample showed a few clusters of cells with abnormal three-dimensional structure, interpreted as adenocarcinoma. These cells were small and had minimal cytologic atypia, demonstrating a potential diagnostic pitfall. The following biopsy confirmed lung adenocarcinoma with the micropapillary pattern. Here, we describe this case and discuss the differential diagno-
1 Department of Anatomic Pathology, Buddhist Dalin Tzu Chi General Hospital, Chiayi, Taiwan 2 Department of Pathology, Da Chien General Hospital, Miaoli, Taiwan 3 Department of Pathology, Taichung Veterans General Hospital, Tachiung, Taiwan *Correspondence to: Nien-Yi Chang, M.D., Department of Pathology, Da Chien General Hospital, Miaoli, Taiwan. E-mail: [email protected] Received 30 April 2013; Revised 20 November 2013; Accepted 9 January 2014 DOI: 10.1002/dc.23104 Published online 19 February 2014 in Wiley Online Library (wileyonlinelibrary.com).
902
Diagnostic Cytopathology, Vol. 42, No 10
sis of pulmonary entities exhibiting similar morphologies. Diagn. Cytopathol. 2014;42:902–905. VC 2014 Wiley Periodicals, Inc. Key Words: sputum
lung adenocarcinoma; micropapillary; cytology;
Sputum cytology is regarded as a simple, inexpensive, and noninvasive test, although its diagnostic sensitivity is low, compared with bronchial brushing.1 In 2011, a new adenocarcinoma classification called the International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society (IASLC/ATS/ERS) International Multidisciplinary Lung Adenocarcinoma Classification2 was published. Most lung cancers are not resectable because of advanced disease stage, and a diagnosis is usually established on the basis of small biopsy specimens and cytology. Therefore, this new classification is relevant to resection specimens, small biopsy specimens, and cytology specimens. Compared with the 2004 World Health Organization classification,3 the IASLC/ATS/ERS committee proposed two new patterns and recommended describing identifiable patterns of adenocarcinoma in small biopsy and cytology specimens. The micropapillary pattern is one of the new patterns and its presence is associated with a poor prognosis. We present a case of lung adenocarcinoma manifesting with the micropapillary pattern on cytology of a sputum sample, which could be a potential diagnostic pitfall that requires differential diagnosis with similar pulmonary entities. C 2014 WILEY PERIODICALS, INC. V
Diagnostic Cytopathology DOI 10.1002/dc
LUNG ADENOCARCINOMA WITH MICROPAPILLARY PATTERN
Fig. 1. A: A few clusters of small-sized cells with three-dimensional structure and overlapping nuclei. Occasionally, isolated atypical cells are present (Papanicolaou stain, sputum, 3400). B: High-magnification view showing a ball-like cluster of tumor cells exhibiting a radiating flower-petal pattern, without a fibrovascular core. The nuclei were small with a high nuclear-cytoplasmic ratio, irregular nuclear outlines, and uneven chromatin distribution (Papanicolaou stain, sputum, 31000; inset, Liu’s stain, bronchial washing, 31000). C: Microcalcification resembling a psammoma body (Papanicolaou stain, sputum, 3400). D: Micropapillary tufts floating within alveolar spaces (hematoxylin–eosin stain, bronchial biopsy, 3400; inset, positive nuclear staining for thyroid transcription factor-1 in the micropapillary component). [Color figure can be viewed in the online issue, which is available at wileyonlinelibrary.com.]
Case Report Clinical History A 75-year-old woman without a prior history of malignancy was referred to our hospital. She presented with a productive cough, blood-tinged sputum, and some symptoms of upper respiratory tract infection. Chest radiography and computed tomography showed consolidation and ground-glass opacities with an air bronchogram in the right lower lung. No obvious mass lesion was noted, giving an initial impression of pneumonia. However, sputum cytology revealed adenocarcinoma. The following biopsy confirmed the presence of adenocarcinoma with the micropapillary pattern.
Cytological and Histological Findings On sputum cytology, only a few clusters of cells with three-dimensional structure and overlapping nuclei were
observed. Occasionally, isolated single atypical cells were also observed (Fig. 1A). At high magnification, the balllike cell cluster exhibited a radiating flower-petal pattern, without fibrovascular cores. The cells were small, displayed a high nuclear-cytoplasmic ratio and scant vacuolated cytoplasm, without intercellular molding. The nuclei demonstrated irregular outlines with uneven chromatin distribution and inconspicuous nucleoli (Fig. 1B). Microcalcifications, resembling psammoma bodies, were also recognized (Fig. 1C). In the bronchial biopsy specimen, small papillary clusters of glandular cells were observed within the alveolar airspace, which did not show fibrovascular cores (Fig. 1D). The tumor cells were small and cuboidal, with minimal nuclear atypia. The tumor nuclei in the biopsy specimen showed positive immunostaining for thyroid transcription factor-1 (Fig. 1D, inset). Further molecular analysis of the tumor revealed a deletion in exon 19 of the epidermal growth factor receptor gene. Diagnostic Cytopathology, Vol. 42, No 10
903
Diagnostic Cytopathology DOI 10.1002/dc
CHANG ET AL.
Fig. 2. A: Reserve cells under the surface columnar epithelium (ciliated bronchial cells) of the respiratory tract (hematoxylin–eosin stain, 3400). B and C: Reserve cells showing small, uniform, tightly cohesive, hyperchromatic cells with scant cytoplasm and smudged, dark, evenly distributed chromatin. Ciliated bronchial cells are seen around the reserve cells (Liu’s stain, B, 3400; C, 31000). [Color figure can be viewed in the online issue, which is available at wileyonlinelibrary.com.]
Discussion Lung cancer is the leading cause of cancer death, worldwide,4 with pulmonary adenocarcinoma being the most common histological type of primary lung carcinoma.3 Adenocarcinomas with predominantly solid or micropapillary patterns have significantly poorer prognoses than other types of lung cancers.5–9 The presence of a micropapillary component is associated with a significantly higher incidence of lymph node metastasis, pleural invasion, lymphatic invasion, and venous invasion.10 This pattern of lung adenocarcinoma was first reported by Amin et al.11 in 2002 and is characterized by small papillary tufts that lack fibrovascular cores, which may be detached and/or connected to the alveolar walls. The tumor cells are usually small and cuboidal with minimal nuclear atypia; psammoma bodies may be seen.2 Although cytologic criteria for the different subtypes of lung adenocarcinoma in different cytologic preparations have yet to be established, some unusual features were demonstrated in the sputum cytology of this patient. The tumor cells in this case were small and cuboidal, with nuclei that were 1–2 times the size of small lymphocytes without macronucleoli. The ball-like cell clusters exhibited a radiating flower-petal pattern without fibrovascular cores, and with fewer than 50 cells in each cell cluster. The tumor cells did not demonstrate glandular structures with central lumens or cohesive cell clusters in a sheet-like pattern, but psammoma body-like microcalcifications were evident. Although possibly nonspecific, these are easily observed in tumors with micropapillary features, e.g., papillary serous adenocarcinoma of the ovary. The most important differential diagnosis was reserve cell hyperplasia. Reserve cells are immature cells present under the surface columnar epithelium (ciliated bronchial 904
Diagnostic Cytopathology, Vol. 42, No 10
cells) of the respiratory tract (Fig. 2A). Reserve cells proliferate when the surface epithelium is shed during chronic irritation or lung injury. Cytomorphologically, reserve cell hyperplasia appears as small, uniform, tightly cohesive, hyperchromatic cells with scant cytoplasm and smudged, dark, evenly distributed chromatin; single cells are not seen (Fig. 2B). A few ciliated bronchial cells may be observed around the reserve cells (Fig. 2C). These cell clusters lack three-dimensional structure, nuclear molding, and evidence of mitosis or necrosis. Other differential diagnoses should include pulmonary entities that exhibit similar morphology, such as small cell carcinoma and carcinoid tumor.12 Some useful cytological features for the differential diagnosis of similar lesions are summarized in Table I. Does the cytological micropapillary pattern correlate with the histological subtyping? Rudomina et al.13 compared specific histological types of lung adenocarcinoma with their cytological patterns in fine-needle aspirations and identified micropapillary tufts in 48% of the histologically micropapillary pattern-negative group. Therefore, the detection of micropapillary tufts by fine-needle aspiration cytology does not provide a reliable correlation with the histological micropapillary component. The cytological preparation from an aspirated sample is often three dimensional, as it usually contains structured fragments of tissues that were removed in toto from their setting.14 Thus, the micropapillary tufts observed in fine-needle aspiration cytology are possibly the result of the negative pressure manipulations of the needle, not necessarily representing the histological micropapillary component. Sputum cytology, on the other hand, involves exfoliated material. Because the micropapillary component often floats within the alveolar spaces, it can spread aerogenously.10,15 As this case suggests, the micropapillary tufts in sputum cytology may correlate better with the
Diagnostic Cytopathology DOI 10.1002/dc
LUNG ADENOCARCINOMA WITH MICROPAPILLARY PATTERN Table I. Cytological Features of Pulmonary Entities Exhibiting Similar Morphology Adenocarcinoma with micropapillary pattern
Reserve cell hyperplasia
Focal necrotic Three-dimensional clusters, single cells, nuclear overlapping Scant, vacuolated Small, occasional mitosis Irregular Hyperchromatic, unevenly distributed/ occasional nucleoli Variable
Non-necrotic Cohesive clusters, no single cell, surrounding ciliated cells Scant, indistinct Small, rare mitosis Smooth Hyperchromatic, evenly distributed/indistinct nucleoli Rare
Cytological features Background Pattern Cytoplasm Nuclei Nuclear membrane Chromatin/nucleoli Incidence in sputum
histological micropapillary component. However, because this report represents a single case, the value of this apparent association will require the study of more cases for validation. In summary, although the diagnostic sensitivity of sputum samples is low, the micropapillary pattern, indicative of a poor prognosis, may be evident in these samples. The cytopathologist should be aware of the cytological features of adenocarcinoma manifesting with the micropapillary pattern in sputum and, when present, alert the clinician to perform further examinations to avoid delayed diagnosis and treatment.
Acknowledgments The authors thank the Department of Pathology of Taichung Veterans General Hospital, especially Professor Dr. John Wang, for their assistance in diagnosis.
References 1. Bedrossian CW, Rybka DL. Bronchial brushing during fiberoptic bronchoscopy for the cytodiagnosis of lung cancer: Comparison with sputum and bronchial washings. Acta Cytol 1976;20:446–453. 2. Travis WD, Brambilla E, Noguchi M, et al. International association for the study of lung cancer/American thoracic society/European respiratory society international multidisciplinary classification of lung adenocarcinoma. J Thorac Oncol 2011;6:244–285. 3. Travis WD, Brambilla E, Muller-Hermelink HK, Harris CC, editors. WHO Classification of tumors. Pathology and genetics of tumours of the lung, pleura, thymus and heart. Lyon: IARC Press; 2004. p 35–44. 4. Hoffman PC, Mauer AM, Vokes EE. Lung cancer. Lancet 2000; 355:479–485. 5. Russell PA, Wainer Z, Wright GM, Daniels M, Conron M, Williams RA. Does lung adenocarcinoma subtype predict patient survival? A clinicopathologic study based on the new International Association for the Study of Lung Cancer/American Thoracic Soci-
Small cell carcinoma
Carcinoid tumor
Necrotic Loose cluster, Indian-file arrangement, nuclear molding Scant, easily stripped Small, Brisk mitosis Smooth Granular, evenly distributed/ indistinct nucleoli
Non-necrotic Loose clusters, dispersive single cells, no nuclear molding Moderate, often stripped Small, rare mitosis Smooth Granular, stippled, “salt and pepper”/distinct small nucleoli Rare
Common
ety/European Respiratory Society international multidisciplinary lung adenocarcinoma classification. J Thorac Oncol 2011;6:1496– 1504. 6. Yoshizawa A, Motoi N, Riely GJ, et al. Impact of proposed IASLC/ATS/ERS classification of lung adenocarcinoma: Prognostic subgroups and implications for further revision of staging based on analysis of 514 stage I cases. Mod Pathol 2011;24:653–664. 7. Warth A, Muley T, Meister M, et al. The novel histologic international association for the study of lung cancer/American thoracic society/European respiratory society classification system of lung adenocarcinoma is a stage-independent predictor of survival. J Clin Oncol 2012;30:1438–1446. 8. Woo T, Okudela K, Mitsui H, et al. Prognostic value of the IASLC/ATS/ERS classification of lung adenocarcinoma in stage I disease of Japanese cases. Pathol Int 2012;62:785–791. 9. Gu J, Lu C, Guo J, et al. Prognostic significance of the IASLC/ ATS/ERS classification in Chinese patients-A single institution retrospective study of 292 lung adenocarcinoma. J Surg Oncol 2013; 107:474–480. 10. Zhang J, Liang Z, Gao J, Luo Y, Liu T. Pulmonary adenocarcinoma with a micropapillary pattern: A clinicopathological, immunophenotypic and molecular analysis. Histopathology 2011;59: 1204–1214. 11. Amin MB, Tamboli P, Merchant SH, et al. Micropapillary component in lung adenocarcinoma: A distinctive histologic feature with possible prognostic significance. Am J Surg Pathol 2002;26:358– 364. 12. Idowu MO, Powers CN. Lung cancer cytology: Potential pitfalls and mimics—A review. Int J Clin Exp Pathol 2010;3:367–385. 13. Rudomina DE, Lin O, Moreira AL. Cytologic diagnosis of pulmonary adenocarcinoma with micropapillary pattern: Does it correlate with the histologic findings? Diagn Cytopathol 2009;37:333–339. 14. Koss LG, Melamed MR. Koss’ diagnostic cytology and its histopathologic bases. 5th ed. Vol. 2. Philadelphia: Lippincott Williams & Wilkins; 2006. p 1056–1080. 15. Prior JO, Stupp R, Christodoulou M, Letovanec I. Micropapillary pattern in lung adenocarcinoma: Aspect on 18F-fluorodeoxyglucose positron emission tomography/computed tomography imaging. Interact Cardiovasc Thorac Surg 2010;10:144–145.
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