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Squamous Cell and
Adenocarcinoma of the Lung
Squamous Cell and
Adenocarcinoma of the LungErica Reinig,M4
CUMC
Dept of PathologyJuly 30, 2010
Erica Reinig,M4
CUMC
Dept of PathologyJuly 30, 2010
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E.C.: Patient HistoryE.C.: Patient History 68 year old African American female
Moderately differentiated squamous cell
carcinoma of left lower lung, stage 1, s/pleft lower lobectomy in 2007.
Small left pleural effusion (5/08)
Mediastinal LN positive for squamous cellcarcinoma. Diagnosed by FNA (12/08)
Recurrent NSCLC Stage IV (06/10).
68 year old African American female
Moderately differentiated squamous cell
carcinoma of left lower lung, stage 1, s/pleft lower lobectomy in 2007.
Small left pleural effusion (5/08)
Mediastinal LN positive for squamous cellcarcinoma. Diagnosed by FNA (12/08)
Recurrent NSCLC Stage IV (06/10).
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Left Lower Lobectomy, 07Left Lower Lobectomy, 07
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Mediastinal LN, 08Mediastinal LN, 08
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Chemo/RadiationChemo/Radiation 1/21/09: Cisplatin, VP-16, radiation
3/10/09: Completed Cisplatin
5/27/09: Taxol/Carboplatin
8/25/09: Three cycles Taxol andCarboplatin completed
07/08/10: Received first Taxol/Carboplatintreatment of new round of chemotherapy forStage IV recurrence.
1/21/09: Cisplatin, VP-16, radiation
3/10/09: Completed Cisplatin
5/27/09: Taxol/Carboplatin
8/25/09: Three cycles Taxol andCarboplatin completed
07/08/10: Received first Taxol/Carboplatintreatment of new round of chemotherapy forStage IV recurrence.
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Additional HistoryAdditional History History of PE
Hypertension
Hyperlipidemia
COPD, on 2L of oxygen at home
Glaucoma
Cardiac arrhythmia
C-spine surgery Hysterectomy age 38
Smoking history: 50 pack year hx, quit in 07
EtOH: Quit 20 years ago
History of PE
Hypertension
Hyperlipidemia
COPD, on 2L of oxygen at home
Glaucoma
Cardiac arrhythmia
C-spine surgery Hysterectomy age 38
Smoking history: 50 pack year hx, quit in 07
EtOH: Quit 20 years ago
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Clinical PresentationClinical Presentation Went to ER last weekend in June, complaints of
SOB. CT at this time showed increase inpulmonary nodules.
Presented to CUMC on 7/08/10 with complaints
of SOB and chest pain. Subsequently admitted. Seen in Heme/Onc clinic that morning
Chest pain: 8/10, central, improved with 2 nitro
No a/a factors, no radiation, no N/V
Pain started night prior, was dull and intermittent Patient pale, diaphoretic, +JVD, diastolic murmur,
hypotensive
EKG changes: T wave inv. & ST elevation in V1, V2,V3, III
Went to ER last weekend in June, complaints ofSOB. CT at this time showed increase inpulmonary nodules.
Presented to CUMC on 7/08/10 with complaints
of SOB and chest pain. Subsequently admitted. Seen in Heme/Onc clinic that morning
Chest pain: 8/10, central, improved with 2 nitro
No a/a factors, no radiation, no N/V
Pain started night prior, was dull and intermittent Patient pale, diaphoretic, +JVD, diastolic murmur,
hypotensive
EKG changes: T wave inv. & ST elevation in V1, V2,V3, III
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Clinical CourseClinical Course High suspicion of PE, started on heparin.
Pulmonary and Cardiology consults
Echo and EKG changes consistent with right heartstrain--PE vs. less likely anteroseptal ischemia
LE Dopplers negative for DVT 7/9/10
CT showed no evidence of PE. Did show opacity,
bronchopneumonia vs. MAC vs. hematologicalspread of cancer 7/9/10
UE Dopplers showed acute non-occlusive DVT inleft axillary and proximal brachial vein 7/10/10
High suspicion of PE, started on heparin.Pulmonary and Cardiology consults
Echo and EKG changes consistent with right heartstrain--PE vs. less likely anteroseptal ischemia
LE Dopplers negative for DVT 7/9/10
CT showed no evidence of PE. Did show opacity,
bronchopneumonia vs. MAC vs. hematologicalspread of cancer 7/9/10
UE Dopplers showed acute non-occlusive DVT inleft axillary and proximal brachial vein 7/10/10
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Clinical CourseClinical Course 7/10/10 at around 16:00
Patient unresponsive with worsening O2 sats.
Code called
Patient hypoxemic, bradycardic
Respiratory arrest, intubation
Pronounced dead after code failed to regaincardiac activity
7/10/10 at around 16:00
Patient unresponsive with worsening O2 sats.
Code called
Patient hypoxemic, bradycardic
Respiratory arrest, intubation
Pronounced dead after code failed to regaincardiac activity
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Autopsy, Thoracic OnlyAutopsy, Thoracic Only Time of Death: 7/10/10 at 16:10
Gross Findings:
Enlarged left supraclavicular, mediastinal, and tracheal
lymph nodes
Coronary atherosclerosis
Concentric left and right ventricular hypertrophy
Left lung: area of fibrosis and lesion at hilum
Right lung: nodularity of upper and lower lobes
Time of Death: 7/10/10 at 16:10
Gross Findings:
Enlarged left supraclavicular, mediastinal, and tracheal
lymph nodes
Coronary atherosclerosis
Concentric left and right ventricular hypertrophy
Left lung: area of fibrosis and lesion at hilum
Right lung: nodularity of upper and lower lobes
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Microscopic FindingsMicroscopic Findings Cardiovascular:
Right ventricular myocyte hypertrophy
RCA 50% stenosis, LAD 75% stenosis, LCx 50%
stenosis Respiratory:
Increased alveolar space
Diffuse fibrosis
Adenocarcinoma w/ vascular invasion. Hematopoietic:
Supraclavicular, mediastinal, paratracheal nodesdemonstrate adenocarcinoma w/ vascular invasion on
peritracheal section
Cardiovascular: Right ventricular myocyte hypertrophy
RCA 50% stenosis, LAD 75% stenosis, LCx 50%
stenosis Respiratory:
Increased alveolar space
Diffuse fibrosis
Adenocarcinoma w/ vascular invasion. Hematopoietic:
Supraclavicular, mediastinal, paratracheal nodesdemonstrate adenocarcinoma w/ vascular invasion on
peritracheal section
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Right middle lobe: Increased alveolar space, fibrosisRight middle lobe: Increased alveolar space, fibrosis
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Right middle lobe: AdenocarcinomaRight middle lobe: Adenocarcinoma
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Right middle lobe: Vascular invasionRight middle lobe: Vascular invasion
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Right middle lobe: Vascular invasionRight middle lobe: Vascular invasion
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Peritracheal vascular invasionPeritracheal vascular invasion
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Peritracheal vascular invasionPeritracheal vascular invasion
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Lung CancerLung Cancer
Most common cause of cancer mortality
worldwide
Peak incidence in 40-70 age group
1 year survival rate: 41%
5 year survival rate: 15%
Etiology
Most common cause of cancer mortality
worldwide
Peak incidence in 40-70 age group
1 year survival rate: 41%
5 year survival rate: 15%
Etiology
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Carcinomas of the LungCarcinomas of the Lung Metastatic
Adenocarcinoma (38%)
Squamous Cell Carcinoma (20%)
Small cell carcinoma (13%)
Large cell carcinoma (5%)
Metastatic
Adenocarcinoma (38%)
Squamous Cell Carcinoma (20%)
Small cell carcinoma (13%)
Large cell carcinoma (5%)
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Clinical PresentationClinical Presentation Cough
Hemoptysis
Weight loss Chest pain
Shortness of breath
Fatigue
Fever
Depression
Metastasis
Cough
Hemoptysis
Weight loss Chest pain
Shortness of breath
Fatigue
Fever
Depression
Metastasis
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Common Sites of MetastasisCommon Sites of Metastasis Adrenal glands--most frequent site
Liver--50% NSCLC patients on autopsy
Bone--20% NSCLC patients on
presentation
Brain--More frequent with adenocarcinoma
than squamous cell
Adrenal glands--most frequent site
Liver--50% NSCLC patients on autopsy
Bone--20% NSCLC patients on
presentation
Brain--More frequent with adenocarcinoma
than squamous cell
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Paraneoplastic SyndromesParaneoplastic Syndromes SIADH: hyponatremia (Small cell)
ACTH: Cushing syndrome (Small cell)
Parathyroid hormone-related peptide:hypercalcemia (Squamous cell)
Calcitonin: hypocalcemia
Gonadotropins: gynecomastia Bradykinin and serotonin: carcinoid
syndrome (Carcinoid tumor)
SIADH: hyponatremia (Small cell)
ACTH: Cushing syndrome (Small cell)
Parathyroid hormone-related peptide:hypercalcemia (Squamous cell)
Calcitonin: hypocalcemia
Gonadotropins: gynecomastia Bradykinin and serotonin: carcinoid
syndrome (Carcinoid tumor)
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Work-upWork-up Labs: CBC, electrolytes, calcium, AST,
ALT, alkaline phosphatase, billirubin,
creatinine Imaging: CT (including lungs, liver, and
adrenals), may require PET, CT brain,PET/CT
Tissue sampling: necessary for diagnosisand staging.
Labs: CBC, electrolytes, calcium, AST,ALT, alkaline phosphatase, billirubin,
creatinine Imaging: CT (including lungs, liver, and
adrenals), may require PET, CT brain,PET/CT
Tissue sampling: necessary for diagnosisand staging.
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Squamous CellSquamous Cell Closely correlated with smoking
More common in men
More common in segmental or subsegmental
bronchi Histology
Keratinization: squamous pearls, eosinophiliccytoplasm
Intracellular bridges Highest frequency p53
Commonly have overexpression EGFR,occassional HER-2/neu
Closely correlated with smoking
More common in men
More common in segmental or subsegmental
bronchi Histology
Keratinization: squamous pearls, eosinophiliccytoplasm
Intracellular bridges Highest frequency p53
Commonly have overexpression EGFR,occassional HER-2/neu
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Squamous CellSquamous Cell
Image from pathologyoutlines.com Image from pathologyoutlines.com
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AdenocarcinomaAdenocarcinoma Most common type of lung carcinoma in women
and nonsmokers
Tumors are more peripherally located
Histology Glandular differentiation or mucin production
Acinar, papillary, bronchioloalveolar type
K-RAS mutations Similar frequency of p53, RB, and p16 as
squamous cell
Most common type of lung carcinoma in womenand nonsmokers
Tumors are more peripherally located
Histology Glandular differentiation or mucin production
Acinar, papillary, bronchioloalveolar type
K-RAS mutations Similar frequency of p53, RB, and p16 as
squamous cell
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AdenocarcinomaAdenocarcinoma
Image from American Journal of Clinical Pathology. 2009;131(1):122-128. 2009
American Society for Clinical Pathology
Image from American Journal of Clinical Pathology. 2009;131(1):122-128. 2009
American Society for Clinical Pathology
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The Clinical BreakdownThe Clinical Breakdown Small cell
Frequently metastatic
Responds well to chemotherapy
Non-small cell
Not as frequently metastatic
Does not respond as well to chemotherapy
Small cell
Frequently metastatic
Responds well to chemotherapy
Non-small cell
Not as frequently metastatic
Does not respond as well to chemotherapy
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StagingStaging T1: Tumor 3 cm or involvement of main stem bronchus 2 cm fromcarina, visceral pleural involvement, or lobar atelecrasis
T3: Tumor with involvement of chest wall (including superior sulcustumors), diaphragm, mediastinal pleura, pericardium, main stembronchus 2 cm from carina, or entire lung atelectasis
T4: Tumor with invasion of mediastinum, heart, great vessels, trachea,
esophagus, vertebral body, or carina or with a malignant pleuraleffusion
N0: No demonstrable metastasis to regional lymph nodes
N1: Ipsilateral hilar or peribronchial nodal involvement
N2: Metastasis to ipsilateral mediastinal or subcarinal lymph node
N3: Metastasis to contralateral mediastinal or hilar lymph nodes,ipsilateral or contralateral scalene, or supraclavicular lymph nodes
M0: No (known) distant metastasis
M1: Distant metastasis
T1: Tumor 3 cm or involvement of main stem bronchus 2 cm fromcarina, visceral pleural involvement, or lobar atelecrasis
T3: Tumor with involvement of chest wall (including superior sulcustumors), diaphragm, mediastinal pleura, pericardium, main stembronchus 2 cm from carina, or entire lung atelectasis
T4: Tumor with invasion of mediastinum, heart, great vessels, trachea,
esophagus, vertebral body, or carina or with a malignant pleuraleffusion
N0: No demonstrable metastasis to regional lymph nodes
N1: Ipsilateral hilar or peribronchial nodal involvement
N2: Metastasis to ipsilateral mediastinal or subcarinal lymph node
N3: Metastasis to contralateral mediastinal or hilar lymph nodes,ipsilateral or contralateral scalene, or supraclavicular lymph nodes
M0: No (known) distant metastasis
M1: Distant metastasis
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StagingStaging Stage Ia: T1, N0, M0
Stage Ib: T2, N0, M0
Stage IIa: T1, N1, M0
Stage IIb: T2, N1, M0 or T3, N0, M0
Stage IIIa: T1-3, N2, M0 or T3, N1, M0
Stage IIIb: Any T, N3, M0 or T3, N2, M0 or T4,any N, M0
Stage IV: Any T, any N, M1
Stage Ia: T1, N0, M0
Stage Ib: T2, N0, M0
Stage IIa: T1, N1, M0
Stage IIb: T2, N1, M0 or T3, N0, M0
Stage IIIa: T1-3, N2, M0 or T3, N1, M0
Stage IIIb: Any T, N3, M0 or T3, N2, M0 or T4,any N, M0
Stage IV: Any T, any N, M1
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Table from Midthun, D.E. (2010) Adenocarcinoma of unknown primary site.
www.uptodate.com
Table from Midthun, D.E. (2010) Adenocarcinoma of unknown primary site.
www.uptodate.com
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ManagementManagement Surgical resection
Chemotherapy, mostly platinum based
Targeted therapy, ex. monoclonal antibody
against EGFR
Radiation therapy
Postoperative and adjuvant chemo or
radiation
Surgical resection
Chemotherapy, mostly platinum based
Targeted therapy, ex. monoclonal antibody
against EGFR
Radiation therapy
Postoperative and adjuvant chemo or
radiation
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Something to considerSomething to consider Article from NYTimes.com
Cancer Funding: Does It Add Up?
N.C.I. Fund distribution per death
Lung (162,460): $1,630
Colon (55,170): $4,566
Breast (41,430): $13,452
Prostate (27,350): $11,298
Article from NYTimes.com
Cancer Funding: Does It Add Up?
N.C.I. Fund distribution per death
Lung (162,460): $1,630
Colon (55,170): $4,566
Breast (41,430): $13,452
Prostate (27,350): $11,298
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Questions?Questions? Thanks to Susan Marion, M.D., for all of
her help!
Thanks to Susan Marion, M.D., for all of
her help!
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ReferencesReferences Adenocarcinoma of the lung. www.pathologyoutlines.com.
Hainsworth & Greco (2010). Adenocarcinoma of unknown primary site.UpToDate. Retrieved July 28, 2010, from www.uptodate.com.
Herbst, et al. (2009). Evidence based criteria, metastatic breast cancer fromprimary lung, results. American Journal of Clinical Pathology 131(1): 122-128.
Kumar, Abbas, & Fausto (Eds.) (2005). Robbins and Cotran Pathologic Basisof Disease. Philadelphia: Elsevier.
Midthun, D.E. (2010). Overview of the risk factors, pathology, and clinicalmanifestations of lung cancer. UpToDate. Retrieved July 28, 2010, from
www.uptodate.com. Parker-pope, T. (March 6, 2008). Cancer Funding: Does It Add Up?
www.NYTimes.com.
Schild & Ramalingam (2010). Management of stage III non-small cell lungcancer. UpToDate. Retrieved July 28, 2010, from www.uptodate.com.
Adenocarcinoma of the lung. www.pathologyoutlines.com.
Hainsworth & Greco (2010). Adenocarcinoma of unknown primary site.UpToDate. Retrieved July 28, 2010, from www.uptodate.com.
Herbst, et al. (2009). Evidence based criteria, metastatic breast cancer fromprimary lung, results. American Journal of Clinical Pathology 131(1): 122-128.
Kumar, Abbas, & Fausto (Eds.) (2005). Robbins and Cotran Pathologic Basisof Disease. Philadelphia: Elsevier.
Midthun, D.E. (2010). Overview of the risk factors, pathology, and clinicalmanifestations of lung cancer. UpToDate. Retrieved July 28, 2010, from
www.uptodate.com. Parker-pope, T. (March 6, 2008). Cancer Funding: Does It Add Up?
www.NYTimes.com.
Schild & Ramalingam (2010). Management of stage III non-small cell lungcancer. UpToDate. Retrieved July 28, 2010, from www.uptodate.com.