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"Identifying respiratory disease in pathology" will look at the entire spectrum of making a pathology diagnosis. We will start by explaining various specimen collection methods. Once the specimen is collected and processed in histology or cytology, the presentation will then look at different staining techniques and IHC/molecular methods used to make a diagnosis. The presentation will conclude with a few case studies that will incorporate the presentation to diagnosis of a respiratory condition.
- Learn the types of cells found in respiratory pathology.
- Understand proper specimen collection methods.
- Identify IHC stains and molecular techniques used in common diagnoses
Allison Eck is the lead histotechnologist at Doylestown Hospital in Pennsylvania. She has been a histotechnologist for 15 years after graduating with a degree in histotechnology from Harford Community College in Maryland and a bachelor’s degree in biology from Lycoming College in Pennsylvania. She holds her histotechnologist (HTL) and qualification in laboratory safety (QLS) certifications through the ASCP, as well as her Allied Health Instructor (AHI) certification through AMT. Allison has spoken at a variety of professional conferences on respiratory disease as well as lab safety and ergonomics.
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The objectives for today: I will be looking at differentiating the types of cells found in respiratory pathology. We’re going to describe collection methods of respiratory specimens and identify IHC and molecular techniques used to diagnose respiratory diseases.
So the first place to start is the lung anatomy. We're going to focus more on the lower respiratory tract during this webinar. There are three lobes on the right side of the lungs and the left is two lobes and they're separated in the middle by the mediastinum. Lungs are brown and spongy and the right weighs somewhere around 600 grams, the left somewhere around 550 grams. The trachea brings inhaled air into the lungs through tubular branches called bronchi. The bronchi then divide into smaller branches called bronchioles. These bronchioles end in clusters of microscopic air sacs called alveoli. In the alveoli oxygen is absorbed into the blood and then carbon dioxide then travels from the blood to the alveoli and is exhaled out.The lungs are covered by a thin layer of tissue called the pleura. The pleura also lines the inside of the chest cavity. A thin layer of fluid acts as a lubricant which allows the lungs to move freely as they expand and contract with inhalation and exhalation.
COPD and Asthma
So while we're going to focus this webinar on respiratory diseases that require pathologic diagnosis, there's a couple I just want to touch on that don’t need pathology to be diagnosed. Chronic obstructive pulmonary disease or COPD is damage to the lungs that results in difficulty exhaling air out. This will cause shortness of breath and is usually caused by smoking. Emphysema is another form of COPD where the alveoli are damaged and air gets trapped in the lungs and this is also common in smokers. Asthma is caused when the bronchi become inflamed and spasm, and this can cause shortness of breath and wheezing.
Before we look at once it gets to the lab, we want to start with how specimens are collected. We're going to look at radiological guided biopsies and fine needle aspirations, bronchoscopies, endobronchial ultrasounds and transbronchial needle aspirates.And then the thoracotomy and the video assisted thorascopic surgery, which includes wedge resections, lobectomies, andpneumonectomies.
And just as a reminder, as per the Joint Commission standards, all specimens must be labeled with two identifiers. This can be the patient's full name, patient's date of birth,their medical record number and it's always nice to have the specimen collection site on the container itself as well.
Starting with a radiology guided biopsy or fine needle aspiration. The patient is placed on the CT table, the nodule is identified via radiology, and a hollow needle is then placed transcutaneously into the nodule.During a fine needle aspiration, a fine gauge needle and a syringe withdraw fluid or clusters of cells. In the core needle biopsy, an automated mechanism is activated, moving a needle forward and filling a needle trough or shallow receptacle with cores of tissue. The outer sheath of this mechanism instantly moves forward and it cuts the tissue while keeping it in the trough. Usually you want to repeat this about three to six times to make sure we are going to get an adequate diagnosis. The nice part about this is it's done, you’re in and out and all you need as a little band-aid once you're finished with the procedure.
Types of specimens that are retrieved during this procedure are tissue biopsies, these are placed in 10% formalin and then fineneedle aspirations, you can get your needle rinsings which are rinsed inCytolyt. We could do immediate smears, and then we can also, if they’re thought to be infectious, for microbiology the tissue is placed in Thioglycolate.
Moving on to the bronchoscopy. During a bronchoscopy, a viewing tube is used to examine patients’ lungs and airways.Also, the patient's voice box, vocal cords, trachea, and bronchi are examined. There's two types of bronchoscopes. There is a flexible bronchoscope and a rigid bronchoscope. The flexible scopes are much more common these days because they're easy to use and patients only need a twilight sedation. They don’t need a full sedation. If you are going to be using a rigid scope the patient must be placed under full anesthesia. The indications for using the rigid scope over the flexible scope is if a patient is coughing up a large amount of blood, because the suction channels are larger and can accommodate specialized instruments to control bleeding. When the patient is ready for the procedure, the back of the throat and the nose are given a topical lidocaine solution, and then the bronchoscope can be introduced via the nose or the mouth.Even if the patient is under anesthesia, they still will feel an urge to cough just because there’s a sensation of having something inside their trachea.
The types of specimens retrieved during a bronchoscopy are a tissue biopsy, again placed in 10% formalin. These are usually forceps biopsies. Forceps are introduced through the bronchoscope to obtain small pieces of tissue; visible surface lesions are easily biopsied. If we have to go after some deeper lesions, we can use fluoroscopy to obtain the biopsy.
For cytology specimens we can look at brushings, washings, and immediate smears. During the brushing, a soft brush is introduced through the bronchoscope and is brushed along the area of interest. Once the brush is removed, it can be applied to a glass slide to make smears or you can just cut the end of the brush off and put it in a tube of saline. For microbiology specimens, we are going to want to get a bronchoalveolar lavage. This is when a saline solution is introduced through the bronchoscope onto the area of interest and then its suctioned out. This process is repeated a few times just to make sure we get an adequate sample. These can be sent to the lab in saline, or we can add a Carbowax solution to them.
We are going to move on to the endobronchial ultrasound, and this is just an image of what our endobronchial ultrasound lab looks like here. So, the decision to perform the endobronchial ultrasound is really based on whether a histopathologic diagnosis can be rendered on a small sample, and the probability of obtaining diagnostic material. This procedure is best used for neoplasms, infections, and interstitial lung disease. The diagnostic yield for focal lesions using this procedure is really good at about 90 to 100%. For peripheral lung lesions using fluoroscopy and obtaining cytology specimens, the diagnostic yield drops to about 40 to 80%. The diagnostic yield for diffuse lung disease isn't really great at 37%, but if we are going after a diagnosis of sarcoidosis, it actually goes up to 85 to 97%.
There are risks that are involved in this procedure, as with any procedure. They include pneumothorax and bleeding. This happens rarely, in less than 3% of cases. And the endobronchial ultrasound is also really useful in staging lung cancers without using an invasive procedure. So, this actually entails two different procedures, an ultrasound and a bronchoscopy. The bronchoscopy portion of the endobronchial ultrasound is the same as we just discussed a few slides back, then the ultrasound part of the procedure involves an ultrasound processor and a balloon catheter that are attached to a probe and then the balloon is inflated with water until it has firm contact on the airway. And again, the endobronchial ultrasound, the bronchoscope is introduced through the airway.
We can utilize this procedure to go after lymph nodes; that is really useful in staging.So, the lymph nodes have been renamed about a few years ago. Now they're all numbered, so the Station 1 is the supraclavicular lymph nodes, Stations 2 through 4 are the superior mediastinal nodes, 2R and 2L are the upper paratracheal right and left, and 4R and 4L are the lower paratracheal right and left. Inferior mediastinal nodes are Stations7 through 9 with 7 being subcarinal and 8 being para-esophageal. Station 10are the hilar nodes and Station 11 arethe interlobar nodes.
The endobronchial ultrasound is going to look exactly like a regular ultrasound would on any other part of the body. And then, here we can see, here is the node that we are going after, the needle that is introduced into the node and then here is the left atrium and the pulmonary artery.
These are just some images. This image is the ultrasound transducer with the needle, and this is just the pictograph of the needle biopsying a lymph node.
The types of specimens retrieved during an endobronchial ultrasound are going to be similar to the ones obtained during a bronchoscopy. You're going to have your tissue biopsy again placed in 10% formalin. We want to use formalin during the endobronchial ultrasound biopsy because it is really going to minimize any of the artifactual changes caused by tissue compression that happens when we obtain these specimens.
The fine needle aspiration, again, it can be collected in saline. This is going to be really good for your cell block preparations and also immediate smears. If any type of lymphoma is suspected, we can collect flow cytometry specimens in RPMI. And then for microbiology we can collect RBAL.
So, moving on to the more invasive procedures, these are going to be the thoracotomy or video assisted thoracotomy surgery specimens. Thoracotomy is full open chest and the VATS is a minimally invasive procedure. They both require full anesthesia, and we're going to start with the smallest and move our way up to the largest with the full removal of the lung.
So, starting with the blebectomy, a pulmonary bleb is a small collection of air between the lung and the outer surface of the lung, and it’s usually found in the upper lobes. If a bleb ruptures the area leaksdeep into the lung cavity, which can cause pneumothorax and can result in collapsed lungs. A blebectomy is removing only the affected part of the lung.
And then moving a little bit bigger, we're going to move to the wedge resection. A wedge resection is a surgical procedure during which the surgeon removes a small wedge-shaped portion of the lung containing either the cancerous cells along with the health healthy tissue that surrounds the area. The surgeries areperformed to remove small tumors or to make a diagnosis of lung cancer. The wedge resection is performed in place of a lobectomy when there is danger of decreased lung function if too much of the lung is removed. Wedge resection can be performed using either the VAT or the thoracotomy procedure. Looking at the blebectomy and the wedge resection for gross dissection, they are usually triangular segments of lungs with two intersecting staple lines. The best way to remove the staples in these specimens is to use a pair of scissors and to cut the staple line, staying as close to the staples as possible.
For all the histotechs out there, we know the hazards of staples in any type of tissue when it hits the microtome blade, so it’sreally great to advise the pathologist or the pathologist assistants that this is a really good way to get rid of all those staples so that they are not shredding the tissue sample, we’re not shredding the tissue sample, and they're really going to be able to get a good diagnosis.
We're going to serially section the specimen at gross. In the sections we're going to look for focal lesions. I want to describe all lesions as to the color, the size, consistency, and relationship to the margin or the pleural surface. And you always want to include at least one cassette of uninvolved parenchyma in addition to the nodule and the margins.
So, moving a little bigger now, we're going to move into the lobectomy. It is a common surgical procedure that removes one lobe of the lung that contains cancerous cells. The surgical procedure removes the cancerous lobe of the lung along with the bronchus that attaches to it. Then the remaining lobes are then reconnected to the remaining segment of the bronchus. This procedure preserves part of the lung and is an alternative to removing the entire lung, which is called a pneumonectomy, which is where we’re going to remove the entire lung. It's often done for cancer of the lung that can't be treated with the removal of smaller portions of the lung, or if there’s multiple nodules scattered amongst the lung. A pneumonectomy must be performed using the open chest thoracotomy procedure.
The gross dissection, when it comes into the lab, first thing we want to do is weigh the specimen and record the dimensions.Then we want to inflate the specimen through the bronchus, so we want to first remove a section of the bronchus and then using a syringe we want to inflate that lung full of formalin. And then once that is completed and had a good time to fix, I will want to sectionalong the parasagittal plane from lateral to medial and we're going to describe any lesions; size, color; consistency, where it is in relationship to the bronchi, and the pleura. We are going to describe the remainder of the lung parenchyma and any lymph nodes that are involved.
So now that we've looked at specimen collection, we can move on to microscopic examination.
The first place to start is normal lung tissue. The bronchiole is located at the terminal end of the respiratory tree. The terminal bronchiole divides into alveolar ducts, which then continue to alveolar sacs. Microscopically, the sacs show aggregates of smooth muscle and collagen and elastic fibers that form rings around the ducts and opening of the alveolar sacs.
There's three classifications of cells in respiratory tissue;there are squamous cells, glandular cells, and neuroendocrine cells.
Taking a look at squamous cells. Squamous cells are flattened and irregularly shaped cells that form a continuous surface. Squamous cells line the surface of the lungs and are involved in the passive transport of gasses. They line the epithelium of the pleural cavity and allow for the passage of fluids in and out. Squamous cell cancers are the most frequently diagnosed cancer in the endobronchial ultrasound material, and malignant cells are large with irregular nuclei and coarse chromatin. They also have dense cytoplasm. Malignant squamous cells invade as irregular but well-defined sheets and nests of tumors cells.
The glandular bronchial cells are a little more varied. They can be cuboidal, columnar, round, or oval. The cytoplasm can be eosinophilic, basophilic, or even clear. And since the presence of intracellular and extracellular mucin is presumptive of adenocarcinoma, using a mucin stain can be extremely valuable in making the diagnosis.Because most adenocarcinomas are peripheral or have a peripheral location, it makes them less likely to be diagnosed with the endobronchial ultrasound procedure. These are going to be more likely diagnosed with ACT-guided biopsy or a wedge resection.
The third type of cells are the neuroendocrine cells. These are found in the nasal respiratory epithelium, the laryngeal mucosa, and throughout the respiratory tract, from the trachea all the way to the terminal airways.
So neuroendocrine carcinomas are typically bronchogenic tumors, and they're frequently seen during the endobronchial ultrasound procedures. Some characteristics of neuroendocrine carcinomas, crush artifact is really common in this type of cell. They'll show nuclear molding and sheets of tumor cells will show little to no architecture and can look like a mismatch of spindle or fusiform cells with a high mitotic rate. The nuclei are round, oval, or spindle shaped and usually have a fine granular featureless chromatin.
Aside from the three types of cells, technology can detect a number of other things going on in the respiratory tract. We can look at fungus, viruses, bacteria, benign processes; and I will take a little deeper look into malignancies.
Fungus is found everywhere in the world and fungal infections are ubiquitous worldwide. Fungi are usually eukaryotic and contain no chlorophyll. They can be found either as hyphae or as buds. Looking at this image, we have a PAS stain and it's showing the fungus as hyphae and then in this image, we have a P-PAS for fungus stain, which is demonstrating the bud formation.There are some other common fungal infections usually found in immunocompromised patients. Histoplasmosis can be identified with a Grocott methenamine silver stain. Blastomycosiscan use either the GMS or the PAS stain and coccidioidomycosis, using also either the GMS or the PAS stain.
Another type of fungus that is common is Aspergillus. Aspergillus is found everywhere in nature and there's over 100 known species of Aspergillus. However only 20 of those species are pathogenic to humans. Aspergillus is found most commonly in compost piles, fertile soil, standing water, or that piece of bread or fruit that you left on your counter for a little too long. The most common species is Aspergillus fumigatus and it’s responsible for causing 90% of all infections. It commonly presents as hyphae, as parallel lines, or as a bundle of hyphae with branching alignment. In the first image you can see the bundle with the branching alignment. In the second image we can see, this is a GMS stain, and it’s staining the hyphae in parallel alignment.
Viruses can also be seen. We'll take a look at herpes; herpes simplex 1and 2 can cause pulmonary disease, which is most common in immunosuppressed patients, those with critical burns, and in infants. The herpes infection is usually acquired in the upper airway and can spread to the bronchi, the bronchioles, and the parenchyma. Morphologic alteration of herpes is the ground glass nuclei.The ground glass nuclei look like a bunch of little shattered pieces of glass. And then what will happen is they will all coalesce into a single eosinophilic inclusion that’s surrounded by a well-defined halo, which we can see in this image here.Herpes is best seen with a PEP stain but is really easily overlooked, so using IHC can confirm a diagnosis.
We can take a look at bacteria starting with the acid-fast bacilli. There are currently about 50 species of non-tuberculoid mycobacterium and all of them are considered pathogenic to humans. Mycobacterium tuberculosis is the most virulent of all mycobacterium species. We can use the acid fasting to visualize mycobacterium, but we can’t identify what species it is. The organisms are usually found at the junction of the necrotic and viable tissue and will appear as bright red, thin, and slightly curved bacteria. While acid-fasting stain is the easiest and cheapest to perform in the lab, auramine-rhodamine fluorescent stain is definitely more sensitive.
And then moving over to pneumocystis. This was thought to be a protozoa for many decades, and it doesn't quite fit the mold of most things. But recently it’s been suggested that it is a fungus.It can't be grown in a culture and we're going to use antibiotics to treat it instead of an antifungal. Pneumocystis can be seen on a PEP stain. It will be seen asa foamy eosinophilic cast, but most commonly we’ll use a Grocott methenamine silver stainfor the diagnosis. Using that stain, they are going to appear as 4 to 6, micron, round to collapses, sometimes with dots found inside the cysts.
Moving over to the carcinoid tumors, they can either be typical or atypical,and they are of neuroendocrine origin. So typical carcinoids are argyrophilic, have dense core granules, relatively bland histologic features and usually have a good prognosis. About 80% of them occur in the main lobar or segmented bronchi. There is equal gender distribution, so they’re found equally in males and females with the mean age of diagnosis usually in the forties to fifties and there is no association with smoking. The five-year survival rate of a typical carcinoid is good at 94 to 100%, but then there are also atypical carcinoids.
They feature somewhere between typical personally and small cell carcinomas. The majority of atypical carcinoids are peripheral and associated with smoking. These more often are occurring in men, slightly older with a diagnosis and usually in your fifties to sixties. They do have a poor prognosis with a five-year survival rate of only 25%. They usually require surgery and adjuvant therapy. The distinguishing characteristic between be the atypical over the typical is an increased mitotic activity and tumor necrosis. There are some adjunctive tests that can be used to diagnose carcinoid tumors, both atypical and typical carcinoids are reactive to neuroendocrine markers such as chromogranin and synaptophysin, neuron specific enolase, CD56 and S100.Some differentiating stains; the typical carcinoids will stain positive with the Grimelius silver stain since they are argyrophilic. Atypicalcarcinoids will stain much higher mitotic index with a KI-67 stain.
Amyloidosis is the next thing we’ll take a look at, and amyloid is a generic term for the heterogeneous family of insoluble fibrillary proteins with beta-pleated sheets. The beta-pleated sheets are sticky and they'll stick on top of each other in an accordion-like fashion and it creates a unique staining characteristic. Most commonly we’ll use a Congo red technique to look at amyloid. Under light microscopy it will stain pink and waxy and actually exhibits an apple green birefringence under a polarized scope. When I am going over this stain with my students, I like to tell them that it looks like somebody scribbled on the slide with a pink crayon, it has that waxy crayon appearance. In addition to the Congo red, you can also use an IHC stain to demonstrate amyloid.
Then moving into malignancy, non-small cell lung cancers account for 85to 90% of all lung cancer cases. This occurs more often in smokers, but it is also the most common form of cancer in non-smokers.
There are three types of non-small cell lung cancer, adenocarcinoma and squamous cell carcinoma, which we already talked about the features of those earlier but adenocarcinoma is slow growing and it’s usually discovered in the outer edges of the lung before it’s spread, and squamous cell carcinomas usually occur in the center of the lungs.
Large cell carcinomas actually can occur anywhere and they're usually fast-growing and bulky tumors. They're undifferentiated and they lackthe diagnostic features of the adenocarcinoma or the squamous cell or small cell cancers by light microscopy. Tumor necrosis is really common in these and microscopically the large cell carcinomas will consist of sheets of polygonal cells with large vesicularnuclei, prominent red nucleoli, and abundant cytoplasm.
There is also small cell lung cancer. It usually starts near the center of the chest and the bronchi. These are fast growing and have a tendency to spread rapidly in the early stages and it's really rare for non-smokers to get small cell lung cancer. They’re characterized by cells with finally stippled chromatin, scant cytoplasm, and they will show IHC evidence of neuroendocrine differentiation. Small cell lung cancer usually shows temporary responses to aggressive chemotherapy and radio-therapeutic modalities that non-small cell lung cancers will not respond to.
Additional Studies for Malignancy
Some additional studies for malignancy. Some more adjunctive tests that can be used, TTF-1, orthyroid transcription factor 1 has been detected in pulmonary adenocarcinoma, large cell carcinoma, and small cell carcinomas of the lung, and it's also really useful in detecting primary versus metastatic lesions of the lung. Napsin-A will stain cells of lung adenocarcinoma,but will not stain cells of adenocarcinoma from any other site. It also does not stain squamous cell carcinomas.
And CK7 is really useful for identifying tumors of primary pulmonary origin and squamous cell carcinomas are immuno-reactive for the AE1/AE3 keratin and the CK5/6.
And then this is just animmunohistogram that sort of sums up the previous slide. We are looking at the three different types of malignancies and their response to the different antibodies.
So, some additional adjunctive tests that can be used.These are more for trying to identify metastatic disease. So, something like CDX2 can be used for colorectal cancer. The estrogen and progesterone receptors are good for breast or ovarian or endometrium. GCDFP15 and mammaglobin are good for breast, Melan A/HMB45 for melanoma and PSA/PSAP for those with prostate cancers.
Moving on, we can take a look at some additional studies;we’ll look at some molecular methods. Starting with the ERCC-1, which is excision repair cross complementation group 1. This is an independent predictor of adjutant therapy and negative tumors, tumors that are negative for ERCC-1 will benefit from cisplatin based chemotherapies. The epidermal growth factor receptor is going to be used in non-small cell lung cancers and this is going to be a predicted response to a tyrosine kinase inhibitor. The percent positive will actually provide an accurate prediction of gefitinib treatment on survival, andthis is seen most commonly in patients who are not smokers.
And then we also have the EGFR gene rearrangement deletion. This is a common deletion found at exon 19. This is going to be treated with erlotinib. KRAS is going to be done by PCR and it’sa mutation in the oncogene, usually at the codon 12 and patients who are negative will respond to the same EGFR tyrosine kinase inhibitor treatment. The ALK gene mutation, can be identified using FSH or PCR and the EML4-ALK gene becomes oncogenic either by fusing itself with other genes or it can gain an additional gene copy, or can mutate the DNA code itself. This is found in 5% of non-small cell lung cancers. It is common in non-smokers and patients who have this are going to be treated with crizotinib. Then theROS1 gene rearrangement, it's going to be done by FSH, and it's 1 to 2% of non-small cell lung cancer patients. There's a similar structure to the ALK gene rearrangement causing oncogenesis and patients who have this gene rearrangement are going to respond positively to crizotinib.
And then PD-L1 or the programmed death ligand-1. The presence of the PD-L1 helps tumors cells evade anti-tumor immunity. There are more than two now, but the two that I'm going to focus on are Keytruda and Opdivo, so you have two treatments that are used. Patients who have non-small cell lung cancer who are PD-L1 positive and do not have an EGFR/ALK abnormality can be treated with Keytruda and this can be used in place of chemotherapy or if a platinum-based therapy was used and it didn't work. Opdivo is used to treat patients with metastatic non-small cell lung cancer who are PD-L1 positive. However, these patients can have the EGFR or ALK abnormalities and we're going to use the Opdivo after patients have progression on a platinum-based therapy.
I am going to spend the rest of the time looking at a couple of patient case studies. This is going to look at how they present, what kind of procedures they had, what was submitted to pathology, and how a diagnosis was then rendered.
Clinical history for patient A. She is an 80-year-old female. She is a half a pack a day smoker with a history of colon cancer and no treatment. She also has a history of emphysema. She seen a 70 lb weight loss over the past year, and five years ago she had a bronchoscopy but it was non-diagnostic.
She presented for a CAT scan and a PET scan. These showed a left upper lobe, cavitary lesion7.5 centimeters and increasing in size. It was also PET avid. She also showed a left pleural effusion with mediastinal lymphadenopathy and scattered bilateral subcentimeter nodules.
She had the bronchoscopy performed. There were mucus plugs present. These were aspirated and sent to microbiology and then there is also brushing of the lesion that was done, slides were made and sent for cytology.
And here we have the patient’s image from the bronchoscope and you can see the cavitary lesion that they were going after.
The results from cytology, all her brushing washings were negative for malignancy. Microbiology was actually positive for a candida albicans and positive for mycobacterium branderi. This patient fortunately doesn't have a malignancy but is going to have a pretty hefty dose of triple antibiotics for at least six to 12 months to clear up these infections.
Patient B is a 64-year-old female. She is a non-smoker. She does have a history of breast cancer which was diagnosed in 2005. She had chemotherapy and radiation for the breast cancer and a lung nodule was identified during that time. She had a needle biopsy which was negative. Familial history: her mother is alive, but has ovarian cancer, and father is deceased with lymphoma.
She presented for the CT scan and the PET scan. She had a left lower lobe mass, which is increasing in size. In 2005 it measured 2.4 centimeters and then about 12 years later had increased to 4 centimeters. This was a PET avid lesion, but she did not have any adenopathy.
As I said before, she had the needle biopsy performed in 2005 which was negative. She now presented, now that it is larger, had the endobronchial ultrasound done. She had a TBNA done with immediate slides sent to cytology and a BAL was collected and sent for cytology and for microbiology.
Cytology, all TBNA specimens and washings were negative for malignancy and there is no gross detected in microbiology.
Due to the size increase and her history of breast cancer, they decided that they wanted to go ahead and have a lobectomy just to get that nodule out of there. It is a good thing that they did because she was shown to have well-differentiated adenocarcinoma. It was 4.2 centimeters and it extended to the parietal pleura and she did have three negative nodes. Showing the adenocarcinoma. And the patient, patient B was essentially cured because her margins were clear and her nodes were negative.
Moving on to patient C. Patient C is an interesting case. She is a 48-year-old female half a pack a day smoker in good health. Sheactually was in a motor vehicle accident and came to the emergency room which prompted some imaging studies to make sure everything was okay from the accident. All her blood work was normal.
But, upon the CT scan it actually showed a right upper lobe nodule 2.8 centimeters. It extended to the plural surface and she did have bilateral hilar adenopathy. She went on to have a PET scan that showed two additional PET avid nodules, one in the right middle lobe, and another in the right lower lobe, and she was PET avid lymphadenopathy in4R, 4L, and 7.
So, this is an image of a PET scan and we can see the PET positive tumors showing here and then the PET avid lymphadenopathy highlighting there. She went on to have a CT guided lung biopsy, which showed a non-small cell adenocarcinoma.We did an IHC workup. She was TTF-1 positive and Napsin A positive, so this indicates that it is adenocarcinoma.
She went on to have an endobronchial ultrasound performed for staging. We did TBNA specimens and sent them to cytology,biopsying the nodes. Her 4R lower paratracheal node was positive for adenocarcinoma, but her other two nodes were negative.Microscopic findingsis the adenocarcinoma found in her cytology specimens.
So, this patient went on to be treated with daily radiation and a taxol/carboplatin chemotherapy regimen and then was scheduled for right pneumonectomydue to the fact that she had a nodule in each of the three right lobes.
Patient D is an 83-year-old male. He has a history of obstructive lung disease and prolonged bronchitis. He was a two pack a day smoker for 30 years, but quit in 1985. He has a history of prostate cancer status/post radiation and his mother died of lung cancer at the age of 69.
In January, he had a chest CT and it showed a 2.8 centimeter right lower lobe posterior nodular density. He then had a repeat chest CT in May, and it had enlarged to 4.1 centimeters and showed mediastinal lymphadenopathy. He went on to have a CT- guided lung biopsy, and we did a little bit of a workup on here and could only come up with a poorly defined granuloma, questionable for sarcoidosis. We did a fungal stain and an acid-fast bacilli stain, which were both negative. He was positive for the AE1/AE3 keratin and was negative for PSA, so we knowit’s not metastatic prostate cancer.
He went on to have an EBUS performed to get a definitive diagnosis and we did TBNA specimens and a BAL of the right lower lobe, which showed adenocarcinoma in the bronchoalveolar lavage and in the 4L and 7 lymph nodes.
Some additional studies that we did on this patient. He did not have any evidence of an ALK gene rearrangement or deletion. He is negative for his ROS1 gene rearrangement and we did a PD-L1 for Opdivo, and he was positive at 90%.
The last patient we’re going to take a look at today is a 60-year-old male who has had a chronic cough for two months. He has a 45-pack year smoker. His mother died of lung cancer at age 82. She was also a smoker. Father was a smoker as well, dying of emphysema at age 72.
He went on to have a CT scan showing an enlarging right upper lobe nodule and a PET scan showing an FDG avid right upper lobe nodule with no mediastinal adenopathy. He went on to have the lung biopsied and it showed squamous cell carcinoma and staining positively for CK5 and P63, indicative of the squamous cell carcinoma, negative for the adenocarcinoma markers.Microscopic findings of the squamous cell carcinoma. We did a PD-L1 Keytruda study for him and he was positive for that at 5 to 10%.
That is all that I have for today. I am going to turn this back over to Rick if there are any questions. Thank you.
What is the prognosis for patients who have had a pneumonectomy?
You can definitely live without one of your lungs.You're just going to have a decreased lung function, you’re not going to be out running marathons or anything, but you can definitely live a good quality life with only having one lung.
What role do frozen sections play in the surgical removal of lung tissue?
Frozen samples can be used to determine if a lesion is malignant or not and also want to make sure if the margins are clear of tumor. We’re going to use the frozen so we know how much of the lung to remove. We can go in and just maybe do a wedge resection instead of having to go take out a whole lobe if the margins are clear.
How important are patients’ clinical histories when it comes to certain testing?
I think patient clinical histories are really important and that's why I kind of focus on some clinical cases at the end. A big thing for people in the lab to know is a smoking history. Especially looking at testing for PD-L1, there are separate test versions for smokers versus non-smokers.So knowing which test to do so we know how to best treat a patient in the future. It is also useful if we know any previous cancer histories, kind of help us rule anything in or out.
For patient B she believes it is, why was the adenocarcinoma not identified until the lobectomy was performed?
Unfortunately, I don't really know the answer to that question. I could only assume it’s attributed to sampling.We don't always hit the nodule using a CT guided biopsy or it might be really peripheral so we’re getting a lot of necrotic tissue or just inflammatory tissue instead of those actual cancer cells. I can only speculate, and I can't really say for sure why, but that would be my guess.
Next, what are platinum-based therapies?
I am not an oncologist, so I can't really talk about the nitty-gritty differences of the types of therapies.I can't really answer that question with a really good response. I’m sorry.
Is there any correlation or evidence of increased risk for lung cancer in vaping?
Scientifically I don't know, personally I want to say yes. I mean any time that you're inhaling anything, I think is putting you at risk for damaging cells and possibly creating that malignant environment. I haven't seen any studies that prove it. I think there will probably be studies as time goes on and vaping still continues to be as popular as it is. But I really kind of equate it really on the same lines as smoking.So,I would say yes.
Is there any diagnosis that would prefer histology or cytology over the other?
I like to think of histology and cytology as being really complementary to complementary departments. I would say if I had to pick one, herpes really favors the diagnosis in cytology. But again, we can make the diagnosis using IHC in pathology as well. I think using histology and cytology together and complimentary that is really going to be best for the patient.
Which lymph node map do you use in your lab?
We've gotten away from using the names as far as lower paratracheal or subcarinal and have moved into the stations, using station4R, Station seven, station 11, we have moved that way hospital-wide.
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