Carcinoma of lung: Squamous cell and adenocarcinoma., Presentation by Erica Reinig M4, CUMC, Omaha,

8/8/2019 Carcinoma of lung: Squamous cell and adenocarcinoma., Presentation by Erica Reinig M4, CUMC, Omaha,

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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%


Etiology

Most common cause of cancer mortality

worldwide

Peak incidence in 40-70 age group



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.

Documents

Carcinoma of lung: Squamous cell and adenocarcinoma., Presentation by Erica Reinig M4, CUMC, Omaha,