WEEK 1: Intra-thoracic malignancies

Question 1

What is malignant tumor?

Describe characteristics of a malignant tumor.

Answer 1

 A tumor that tends to grow, invade, and
metastasize.

 The malignant tumor usually has an irregular shape, irregular border and is composed of poorly differentiated cells.
 If untreated, it may result in death

Question 2

What are Intrathoracic Malignancies?

Answer 2

Intrathoracic malignancies refer to cancers that originate within the thoracic cavity, which is the region of the body enclosed by the ribcage and containing vital organs such as the lungs, heart, and mediastinum.

Question 3

Describe the classification of Intrathoracic Malignancies.

Answer 3

Intrathoracic malignancies can be broadly classified into two groups.

 Primary malignant tumors arising from intrathoracic structures and Secondary malignant tumors arising elsewhere but metastasizing to intrathoracic structures

 Primary tumors may arise from lungs, pleura and mediastinal structures.

 Tumors that metastasize to lung are named as metastatic/secondary tumors.

 Metastatic tumors are more frequent than primary tumors

Question 3

Name the following intrathoracic malignancies.
Bronchial epithelium
Alveolar epithelium
Neuroendocrine cells
Thymus
Lymphocytes
Germ cells
Lipocytes/ adipocytes
Blood vessels
Lymphatics

Answer 3

Bronchial epithelium: Squamous cell carcinoma

Alveolar epithelium: Adenocarcinoma

Neuroendocrine cells: neuroendocrine carcinoma

Thymus: Thymoma

Lymphocytes: Lymphoma

Germ cells: Germ cell tumor

Lipocytes/ adipocytes: Lipoma

Blood vessels: Hemangioma

Lymphatics: Lymphangioma

Question 4

Review slides for lung cancer mutations and how they are tested.

Question 5

 Lung cancer is the most common cancer worldwide.

 Lung cancer remained the leading cause of cancer death, with an estimated 1.8 million deaths (18%), followed by colorectal
(9.4%), liver (8.3%), stomach (7.7%), and female breast (6.9%) cancers.

 Cancer of the lung occurs most often between what ages ages , with a peak incidence where?

Answer 5

 Lung cancer is the most common cancer worldwide.

 Lung cancer remained the leading cause of cancer death, with an estimated 1.8 million deaths (18%), followed by colorectal
(9.4%), liver (8.3%), stomach (7.7%), and female breast (6.9%) cancers.

 Cancer of the lung occurs most often between ages 40 and 70 years, with a peak incidence in the 50s or 60s.

Question 6

Outline the risk factors of lung cancer.

Answer 6

1. Tobacco Smoking.
    About 80% of lung cancers occur in active smokers or those who stopped recently.
    There is a nearly linear correlation between the frequency of lung cancer and pack-years of cigarette smoking.
2. Industrial Hazards.
    Certain industrial exposures, such as asbestos, arsenic, chromium, uranium, nickel, vinyl chloride and mustard gas,
   increase the risk of developing lung cancer.
3. High-dose ionizing radiation is carcinogenic.
4. Exposure to radon gas in miner increases the risk of lung

Question 7

Describe the pathogenesis of lung cancer.

Answer 7

 carcinomas of the lung arise by a stepwise
accumulation of oncogenic “driver” mutations that result in the neoplastic transformation of pulmonary epithelial cells.
 lung cancer is initiated the either by activation of oncogenes or the inactivation of tumor suppressor genes, which leads to uncontrolled replication and growth of the cells in the lungs.

Question 8

Describe the precursor lesion of squamous cell carcinoma.

Answer 8

 (A), basal cell (or reserve cell) hyperplasia
 (B), squamous metaplasia
 (C), moderate degree of squamous dysplasia
 (D), severe squamous dysplasia

Dysplasia is characterized by the presence of disordered squamous epithelium, with loss of nuclear polarity, nuclear hyperchromasia, pleomorphism, and mitotic figures.

 Squamous dysplasia may, in turn, progress through the stages of mild, moderate, severe dysplasia and carcinomain-situ (CIS)

 (E) Carcinoma in situ is the stage that immediately precedes invasive squamous carcinoma.

 Apart from the lack of basement membrane disruption in CIS, the cytologic features are similar to those in frank
carcinoma.

 Unless treated, CIS will eventually progress to invasive cancer.

Question 9

Describe precursor lesions of adenocarcinoma.

Answer 9

 (1) atypical adenomatous hyperplasia

 (2) adenocarcinoma in situ
 This might be precursor to adenocarcinoma
 (3) diffuse idiopathic pulmonary neuroendocrine cell hyperplasia.

 This might be precursor to small cell or large cell neuroendocrine carcinoma

 It should be remembered that the term precursor does not imply that progression to cancer is inevitable.

Atypical adenomatous hyperplasia (AAH):
 a pre-invasive lesion for lung adenocarcinoma (picture 4).
 These lesions generally measure 5 mm or less

 Adenocarcinoma in situ (AIS) is a localized (≤3 cm) adenocarcinoma in which growth is
restricted to tumor cells growing along alveolar structures (lepidic growth pattern) and that lacks any invasion.

 Minimally invasive adenocarcinoma (MIA) describes a small, solitary adenocarcinoma (≤3 cm) with a predominantly lepidic growth pattern and ≤5 mm invasion.

 Lepidic-predominant adenocarcinoma is an invasive tumor with this pattern comprising the predominant pattern and with invasion >5 mm.

 This pattern can be combined with acinar, solid, papillary, and micropapillary patterns
in various combinations (Picture 8).

Question 10

Review notes for lung tumors classification on slides.

Question 11

What is the most common type of lung cancer in contemporary series, accounting for approximately one-half of lung cancer cases?

 The World Health Organization (WHO) classification emphasizes that tissue specimens should be managed
not only for pathologic diagnosis, but also to preserve tissue for molecular studies, which have important treatment implications such as use of targeted
therapies for certain subsets of patients

Answer 11

 Adenocarcinoma is the most common type of lung cancer in contemporary series, accounting for approximately one-half of lung cancer cases.

Question 12

Describe the morphology of lung cancer.

Answer 12

This is a peripheral adenocarcinoma of the lung.
Adenocarcinomas and large cell anaplastic carcinomas tend to occur more peripherally in lung.
Adenocarcinoma is the one cell type of primary lung tumor that occurs more often in nonsmokers and in smokers who have quit.

SQUAMOUS CELL CARCINOMA
 Squamous cell carcinoma was the most frequent histologic type of lung tumor in nearly all studies done prior to the mid-1980s.

 The diagnosis of squamous cell carcinoma is predicated upon the presence of keratin production by tumor cells and/or
intercellular desmosomes (referred to as “intercellular bridges”) or by immunohistochemistry (IHC) consistent with squamous cell carcinoma (ie, expression of p40, p63, CK5, CK5/6, or desmoglein).

 For tumors that are nonkeratinizing, IHC is required to distinguish between squamous carcinoma, solid type adenocarcinoma, and large cell carcinoma with a null phenotype.

 The preferable marker is p40, as p63 is not specific for squamous differentiation, and may be seen in adenocarcinomas.

NEUROENDOCRINE TUMORS

 DIPNECH — Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH) is a generalized proliferation of pulmonary neuroendocrine cells that may be confined to the
mucosa of the airways, invade locally to form “tumorlets,” or form invasive NETs.

 The tumorlets are poorly defined with irregular infiltrative margins and a conspicuously fibrotic stroma; they are intimately related to an airway and are ≤5 mm in diameter.

 Several tumor types are grouped based upon shared neuroendocrine features

 These tumors include typical carcinoid, atypical carcinoid, small cell carcinoma and large cell neuroendocrine carcinoma.

 DIPNECH is considered by the WHO to be a preinvasive lesion, and a likely precursor to pulmonary NETs.

LARGE CELL CARCINOMA
 Large cell carcinoma (LCC) is a malignant epithelial neoplasm lacking glandular, squamous, or neuroendocrine differentiation by light microscopy and immunohistochemistry (IHC; typically, p40 and thyroid transcription factor 1 [TTF-1]) negative, and lacking cytologic features of small cell carcinoma.

 usually presents as a large peripheral mass with prominent necrosis.

 Histologically, LCC is characterized by sheets of round to polygonal cells with prominent nucleoli and abundant pale staining cytoplasm without differentiating features.

Question 13

Describe differential diagnoses of lung cancer.

Answer 13

DIFFERENTIAL DIAGNOSIS
 The diagnosis of a primary lung cancer is
clinicopathologic.
 Many metastatic tumors can have a similar morphologic appearance to primary lung cancers.
 A panel of antibodies is typically used in this context.
 Stains such as CK7 (favors lung primary) and CK20 (favors colon primary) along with CDX2 (favors gastrointestinal primary) may be useful in establishing the diagnosis

Question 14

What is a hamartoma?

Answer 14

A hamartoma is a neoplasm in an organ that is composed of tissue elements normally found at that site but growing in a haphazard mass.

Question 15

Review notes for pictures.

Question 16

What is Paraneoplastic syndrome?

Answer 16

Paraneoplastic syndrome is a set of signs and symptoms that can occur when you have cancer.

The symptoms develop when a malignant tumor causes changes in your body that aren’t directly caused by the cancer itself. The tumor may secrete a hormone or protein that affects a particular body system.

 Carcinomas of the lung is associated with a variety of paraneoplastic syndromes:

 Antidiuretic hormone (ADH), inducing hyponatremia due to inappropriate ADH secretion.

 Adrenocorticotropic hormone (ACTH), producing Cushing syndrome.

 Parathormone, parathyroid hormone-related peptide, prostaglandin E, and some cytokines, all implicated in the hypercalcemia often seen with lung cancer.

Question 17

Discuss Tumors of the pleura.

Answer 17

1. Solitary Fibrous Tumor

 Solitary fibrous tumor is a soft-tissue tumor with a propensity to occur in the pleura and, less commonly, in the lung as well as other sites.

 Grossly, solitary fibrous tumor consists of dense fibrous tissue.

 The tumor has variable biologic behavior but often benign.

2. Malignant mesothelioma
    Malignant mesothelioma is a rare and insidious neoplasm with a poor prognosis.

 It arises from mesothelial surfaces of the pleural cavity, peritoneal cavity, tunica vaginalis, or pericardium.

 Malignant pleural mesothelioma (MPM) is the most common type and can be difficult to treat because most patients have advanced disease at
presentation.

 direct invasion of thoracic structures may occur.
o A unilateral pleural abnormality with a large, unilateral pleural effusion.

 ●A pleural mass or rind or diffuse pleural thickening in the absence of a pleural effusion.

 ●Pleural plaques and/or calcifications.

 ●Ipsilateral mediastinal shift due to encasement of lung by a thick ring of tumor and relative ipsilateral lung volume loss.

 It is associated with exposure to asbestos.

Question 18

Describe Investigation strategies for intrathoracic malignancies.

Answer 18

 Sputum cytology-was once the most common specimen for screening as it is easy to obtain.

 Unfortunately, it did not reduce mortality from lung cancer and sensitivity only increases with multiple specimens.

 Bronchial aspirations and washings- bronchial
secretions can be aspirated directly through the
bronchoscope & examine for cells.

 Alternatively, we can wash the bronchial mucosa by instilling saline and then aspirate.

 Centrifuge & make smears.

 Bronchial brushings-a brush is applied to the surface of the bronchial mucosa through a fiberoptic bronchoscope.

 Bronchoalveolar lavage- access more deeper aspects of the respiratory tree than bronchial washings.

 The bronchoscope is wedged into position as far as it can go and distal airway are flushed with sterile saline & then aspirated.

 Particularly useful for the diagnosis of opportunistic infections in immunocompromised patients.

 Bronchial biopsy/tissue

 Percutaneous Needle biopsy

 Lung resection

Question 19

Describe the pathology of mediastinal tumors.

Answer 19

Pathology of mediastinal tumors

 Mediastinal tumors are among the most difficult lesions examined by the surgical pathologist for
several reasons.
 many different types of lesions occur in this
location
 Since many tumors that occur in the mediastinum have overlapping histologic features, one must consider a broad differential diagnosis and perform a thorough evaluation of each specimen, which may include ancillary testing.

Question 20

Classically the mediastinum is divided into four parts.

State the structures found in the 4 parts and possible tumors.

Answer 20

Mediastinal tumours
 General information:

 Classically the mediastinum is divided into four parts:

*The superior mediastinum: - thyroid and parathyroid lesion

*Anterior mediastinum: In this space the thymus is located.
 Thymoma and thymic cyst
 Teratomas (mixed cystic an solid components).

*Middle mediastinum: contains the heart, trachea, bronchi, great vessels, esophagus, the lymphatic tissue.
 lymphoid tissue located.
 Non-Hodgkin lymphomas or Hodgkin disease).

*Posterior mediastinum:
 Mesenchymal neoplasms, neuroblastomas, enterogenic cyst

Question 21

Describe thymomas.

Answer 21

Thymomas
 Gross appearance — Grossly, most thymomas are circumscribed, tan, firm masses.

 They may range from microscopic lesions to tumors over 30 centimeters in diameter.

 Cystic changes may be extensive, and in such cases, the cyst wall should be sampled carefully to search for tumor foci.

 Thymic carcinoma has a morphology and biology that is distinct from thymoma.

 It lacks the lobulated architecture of thymomas and is characterized by cytoarchitectural features of carcinomas similar to those seen in other organs.

Question 22

Descruibe germ cell tumors

Answer 22

GERM CELL TUMORS
 Mediastinal germ cell tumors (GCTs) can occur as primary neoplasms in the mediastinum.

 Whether these tumors represent a malignant transformation of germ cells migrating along the midline during embryogenesis or originate from the primordial cells of the thymus with germ cell potential is still a subject of debate.

 Histologic subtypes — The histologic types of GCTs in the mediastinum are similar to those that occur in the testis and ovary.

Question 23

Describe neurogenic tumors.

Answer 23

Neurogenic tumors
 Neurogenic tumors — Mediastinal neurogenic tumors develop from local peripheral nerves, sympathetic and parasympathetic ganglia, and embryonic remnants of the neural tube.

 The most common neurogenic tumors are Neurofibroma, schwannoma, neuroblastoma.

 They are most frequent in the paravertebral/posterior compartment of the mediastinum.

 Paragangliomas – Paragangliomas are rare mediastinal tumors that usually originate from sympathetic ganglia and commonly secrete catecholamines.

 Mediastinal paraganglioma are most commonly located beneath the aortic arch above the left atrium and adjacent to the ascending aorta and trachea.

Question 24

Describe mediastinal lymphoma.

Answer 24

Mediastinal lymphoma
 Primary mediastinal large B cell lymphoma (PMBL) is an aggressive B cell lymphoma that is thought to arise from thymic (medullary) B cells.

 It has clinicopathologic features that are distinct
from systemic diffuse large B cell lymphoma (DLBCL) and shares some clinical and biologic features with nodular sclerosing classic Hodgkin lymphoma (CHL).

 The tumor is comprised of large cells with variable nuclear features, resembling centroblasts, large centrocytes, or multilobate cells, often with pale or “clear” cytoplasm.

Question 25

State the symptoms of Mediastinal tumors

Answer 25

Symptoms:
 Respiratory distress due to compression of the
airways (cough, wheezing, recurrent respiratory
infections, atelectasis, hemoptysis).

 Dysphagia (compression of the esophagus).

 Hoarseness (compression of the laryngeal nerve).

 They are most frequent in the paravertebral/posterior compartment of the
mediastinum, where they can cause neurologic symptoms by compression.

Question 26

Describe Investigation of Mediastinal tumors.

Answer 26

 Mediastinal masses may be identified incidentally on imaging performed for unrelated reasons (e.g., preoperative) or for the evaluation of symptoms related to the mass.
 Computed tomography (CT) of the chest can confirm the presence of a mediastinal mass identified on plain radiography or other imaging.
 Patient management relies on an accurate definitive diagnosis, which requires an adequate tissue sample.
 This may be obtained either by biopsy (percutaneous, endobronchial, surgical) or as part of a planned therapeutic resection.