Lung Cancer

Lung cancer is one of the most commonly diagnosed cancers worldwide and the leading cause of cancer-related deaths. It frequently develops from premalignant lesions triggered by carcinogens in cigarette smoke, though other risk factors like radon and pollution exposure contribute too. Non-small cell lung cancer and small cell lung cancer are the main subtypes, with key distinctions in growth patterns and treatment approaches. Symptoms like chronic cough, weight loss, and fatigue typically don’t manifest until later stages when prognosis is poor. Early screening with low-dose CT scans for high risk groups enables early detection, which greatly improves survival rates. However, most cases are still caught late. Standard treatments include surgical resection, chemotherapy, radiation and targeted therapies, but resistance is common. Immunotherapy has emerged as a promising treatment option, especially for metastatic lung cancer. Further advances in early diagnosis and treatment will be critical to reduce the burden of this devastating disease. This article will provide an in-depth overview of lung cancer causes, screening, diagnosis, management, and the latest research.

Executive Summary

Palliative Care: When cancer is advanced or recurrent, palliative treatments focus on improving quality of life by managing symptoms. This can include low-dose radiation, surgery to prevent fluid buildup, or medications for pain and other symptoms.
Prognosis: Survival rates vary significantly based on the stage of cancer at diagnosis, with early-stage cancers having much better outcomes. Overall 5-year survival rates have improved to around 25% due to advances in treatment, but lung cancer remains a serious disease with poor long-term survival for advanced stages.
History of Lung Cancer: Lung cancer was rare before widespread tobacco use but became increasingly common in the 20th century. Major advances in imaging, surgical techniques, and systemic therapies have improved diagnosis and treatment over time. The link between smoking and lung cancer was conclusively established in the 1950s-60s.
Types of Lung Cancer: The two major categories are small cell and non-small cell lung cancer, with non-small cell being more common. Non-small cell includes subtypes like adenocarcinoma, squamous cell carcinoma, and large cell carcinoma. These types are differentiated based on their appearance under a microscope, location in the lung, and specific cellular markers.

Origins and Causes of Lung Cancer

Lung cancer is a disease in which malignant (cancerous) cells form in the tissues of the lungs. It begins when healthy lung cells grow out of control and crowd out normal cells. These cancerous cells can invade and destroy healthy lung tissue and spread (metastasize) to other parts of the body through the bloodstream and lymph system. There are two main types: small cell and non-small cell lung cancer, which account for 95% of cases.

Lung cancer begins when cells in the lung start to grow out of control. These cells eventually form a tumor that can spread to other parts of the body. The main causes of lung cancer are smoking and exposure to radon gas or other carcinogens.

Smoking is by far the leading cause of lung cancer. Cigarette smoke contains over 7,000 chemicals, many of which are known carcinogens. These chemicals damage lung cells, causing genetic mutations that lead to uncontrolled cell growth. The longer a person smokes and the more cigarettes smoked per day, the greater their lung cancer risk. Even secondhand smoke exposure increases lung cancer risk. Quitting smoking at any age reduces risk compared to continued smoking.

Radon gas is the second leading cause of lung cancer. Radon is a radioactive gas that comes from the natural breakdown of uranium in soil and rocks. It is odorless and invisible and can leak into homes and buildings through cracks in floors or walls. Breathing in radon exposes lung tissues to radiation, which damages DNA and can cause cancer. Radon levels are higher in some geographic areas and certain types of buildings. Testing and mitigation can reduce radon exposure.

Other risk factors include exposure to asbestos, certain metals, diesel exhaust, air pollution, and other carcinogens, especially in workplace settings. A previous history of lung disease, such as COPD, also increases risk. Family history can play a role, suggesting genetic factors. People with weakened immune systems have higher lung cancer risk. While e-cigarettes are less harmful than regular cigarettes, their long-term risk is still being studied.

Lung cancer can begin in any part of the lung airways and is divided into small cell and non-small cell types. It may not cause symptoms until it has spread. Catching it early via screening in high-risk groups provides the best outcomes. Quitting smoking, radon mitigation, and reducing exposure to carcinogens can help prevent lung cancer.

Detection

Lung cancer is often asymptomatic in its early stages and may be initially detected through screening or incidentally through imaging tests for other conditions.
Screening via annual low-dose CT scans is recommended for those at high risk due to heavy smoking history.
Symptoms such as persistent cough, coughing up blood, chest pain, wheezing, weight loss, fatigue, may prompt further testing.
A chest X-ray or CT scan can detect lung tumors or abnormalities that require further evaluation.

Diagnosis

A biopsy via bronchoscopy, needle biopsy, thoracoscopy or open surgery is done to collect cells or tissue samples for examination under a microscope. This confirms malignancy.
Imaging tests like CT, PET, MRI scans determine size, location, spread of tumors to lymph nodes or other organs.
Lung function tests assess how well the lungs are working.
Molecular testing examines mutations in the tumor that can guide targeted therapies.
The cancer is staged from I (early) to IV (advanced) which indicates treatment options and prognosis.
The type of lung cancer is identified as small cell or non-small cell. The latter includes adenocarcinoma, squamous cell carcinoma and large cell carcinoma.
Immunohistochemistry examines protein biomarkers to further classify tumor cell characteristics.
A multidisciplinary team of specialists reviews results to make an accurate diagnosis and develop an optimal treatment plan.

Early detection and accurate diagnosis of lung cancer is crucial for effective treatment and improved outcomes. Ongoing research aims to identify new screening and diagnostic approaches.

Staging of Lung Cancer

Lung cancer staging is a system used to determine how far the cancer has spread and helps guide treatment options and prognosis. It utilizes information from diagnostic tests to assign a stage from I to IV:

Stage I - The cancer is localized and has not spread beyond the lungs. Stage IA tumors are smaller than 4cm across and limited to one lung section. Stage IB tumors are larger or have spread to nearby lymph nodes.

Stage II - The tumor is larger or has spread to nearby tissues like the chest wall, diaphragm, pleura or lymph nodes. Stage IIA involves one affected area and IIB involves two areas.

Stage III - The cancer has spread extensively within the chest and involves lymph nodes. Stage IIIA may mean the tumor has spread to lymph nodes in the middle of the chest. Stage IIIB indicates spread on both sides of the chest or into vital structures.

Stage IV - The most advanced stage where cancer has metastasized or spread to distant organs like the other lung, liver, bones or brain. This is divided into IVA and IVB based on severity.

Lower numbered stages indicate earlier, more localized disease that often has better prognosis and more treatment options. Higher stages mean more advanced disease that can be harder to treat.

Staging helps:

Determine optimal treatment such as surgery, chemotherapy, radiation, targeted therapy
Provide information about life expectancy and prognosis
Evaluate whether the cancer can be removed surgically
Decide if other treatments like targeted therapy are warranted based on tumor mutations
Assess clinical trial eligibility
Monitor for recurrence after treatment

Accurate lung cancer staging is critical for appropriate patient management and care planning. It may be adjusted as more diagnostic information is obtained.

Treatment of Lung Cancer

Here is a more in-depth look at the main treatment modalities for lung cancer:

Surgury

Lobectomy (removal of a lobe of the lung) is the most common surgery for NSCLC. It may be done via thoracotomy or video-assisted thoracoscopic surgery (VATS).
Pneumonectomy (removal of an entire lung) is done if the tumor is central or extensive.
Segmentectomy or wedge resection (removal of a small portion of lung) can be options for very early cancers or for people with poor lung function.
Lymph node dissection is done to remove lymph nodes that may contain cancer. This staging helps guide the need for adjuvant therapy.

Chemotherapy

Platinum doublets (cisplatin or carboplatin plus another chemo drug) are standard first-line regimen for advanced NSCLC.
Chemotherapy may be given before surgery (neoadjuvant) or after (adjuvant) to reduce recurrence risk.
Combination chemoradiation therapy is used for locally advanced inoperable NSCLC.
Second-line single agent chemo is used when first-line regimens fail. Amrubicin, docetaxel, pemetrexed, nab-paclitaxel are options.

Radiation for lung cancer

Radiation treatment is often used in the treatment of lung cancer. Here we detail the thinking behind this approach and how it is applied and the effects that you might expect.

Curative:

For early stage NSCLC that is medically inoperable due to poor lung function or other high-risk factors, SBRT can provide excellent local control with survival approaching surgical outcomes.
Adjuvant radiation after surgery is used to target any microscopic disease left behind and lower the risk of recurrence, especially for larger tumors or positive nodes.
Definitive radiation alone or chemoradiation is given for locally advanced unresectable NSCLC to try to achieve long-term disease control.

Preventative:

Prophylactic cranial irradiation has been used to reduce the chance of metastases developing in the brain for extensive small cell lung cancer.

How radiation therapy is delivered:

External beam radiation aims photons or proton beams from a machine outside the body. Use of multiple beams from rotating angles can focus high doses on tumors while exposing less normal tissue.
Brachytherapy implants radioactive seeds or wires directly inside or next to tumors, providing very targeted high-dose radiation over a short distance.
SBRT (stereotactic body radiation) uses specialized techniques of extremely focused, high-dose radiation in just a few treatments.
Radiation is planned using 3D CT simulation and often other imaging to map the tumor location exactly.

Palliative:

Radiation is used to shrink tumors that are causing problematic symptoms like pain, bleeding, airway obstruction. Though not curative, palliation of symptoms can improve quality of life.
Radiation is used to treat metastases, such as to the brain or bones, to relieve associated neurological or pain symptoms.
After chemotherapy or targeted therapy to shrink the cancer, radiation can consolidate any remaining local disease.

Other uses:

Radioisotope brachytherapy implants provide localized high-dose radiation especially for endobronchial tumors.
Radiation is used in all stages of lung cancer at some point, whether for cure, symptom relief, or local control in combination with systemic therapy. The many radiation techniques allow it to be tailored for each patient's specific cancer situation.

Effects and side effects of radiation therapy

Acute Side Effects:

Effects on the tumor:

Radiation works by causing DNA damage within cancer cells, leading to cell death. Damage is caused by direct ionization of atoms by X-rays or creation of charged particles that also disrupt DNA.
Tumor cells tend to have impaired DNA repair mechanisms compared to healthy cells, making it harder for them to recover from radiation damage.
Repeated radiation treatments lead to cumulative damage to tumor DNA, causing cancer cell death, tumor shrinkage and ideally long-term local control.
The total radiation dose, dose per fraction, and number of fractions are tailored to maximize tumor cell kill while sparing normal tissues.

Late Side Effects:

Lung damage/scarring (fibrosis) - this can develop months or years after treatment, causing chronic shortness of breath. Limiting radiation dose to the lungs helps prevent this.
Nerve injury - radiation can damage nerves in the chest, leading to pain or weakness in the chest wall, arm or shoulder. Usually temporary but can be permanent.
Heart disease - radiation to the chest increases long-term risk of coronary artery disease. Dose is minimized to the heart.
Esophageal stricture - chronic scarring can tighten and narrow the esophagus. Treated with esophageal dilation.
Bone damage - radiation may weaken bones and increase fracture risk in the area treated.

Side effects:

Fatigue - tiredness begins 2-3 weeks into treatment. Rest periods are needed.
Skin changes - radiation can cause skin redness, irritation, blistering, peeling at the site. Gentle skin care is required.
Cough/shortness of breath - radiation can inflame lung tissue leading to cough and trouble breathing. Steroids may help.
Nausea/vomiting - occurs due to radiation exposure to the stomach and esophagus with certain beam paths. Anti-nausea medication can help.
Hair loss - radiation beams directed through hair follicles may cause localized hair loss. Typically temporary.
Low blood counts - radiation affects the bone marrow leading to reduced blood cells. Counts are monitored.

Mitigation of side effects:

Careful treatment planning utilizing CT/PET scans to map tumor location and minimize exposure of adjacent healthy structures.
Intensity modulated radiation therapy (IMRT) sculpts radiation beams around tumor shape.
On-board imaging verifies tumor position before each treatment.
Limiting total lung radiation dose and volume reduces lung damage risk.

Targeted and Immunotherapy:

Targeted therapy works by attacking specific mutations and pathways that drive cancer cell growth. For example, EGFR mutations trigger constant cell division signals. EGFR inhibitor drugs bind to the mutated EGFR proteins in cancer cells, blocking the abnormal signals that tell them to keep proliferating. This cuts off the out-of-control growth driven by EGFR mutations.

However, over time the cancer develops new mutations that allow resistance to EGFR inhibitors. So the treatment must be changed to a different EGFR drug or otherwise overcome resistance. The key is matching the right targeted drug to shut down the specific molecular abnormality promoting growth of that patient's lung cancer.

Immunotherapy works differently by harnessing the immune system. Lung cancer cells use PD-L1 proteins to bind to PD-1 on T cells and shut down their cytotoxic activity. PD-1 inhibitor drugs block PD-L1 from binding to PD-1. This prevents cancer cells from deactivating T cells and allows the reactivated immune system to recognize and destroy the cancer.

Adding PD-1/PD-L1 immunotherapy to chemo improves survival because it complements the direct cancer cell killing of chemo with enhanced anti-tumor immune attack. The combo helps overcome one of lung cancer's main defenses - escaping the immune system.

So in summary, targeted therapy directly neutralizes specific molecular drivers of cancer growth, while immunotherapy removes the immune suppression that allows cancer to evade attack. Using both approaches together provides the most precise and robust anti-cancer strategy tailored for each patient's specific lung cancer.

Ablation techniques:

Ablation refers to destroying tumors without removing them surgically. Different energy sources are used to essentially burn or freeze the cancer cells, killing them in place within the lung.

Radiofrequency ablation passes electrical currents through needles inserted into the tumor. These currents generate heat that "cooks" the cancer cells, killing them.

Microwave ablation uses electromagnetic microwaves transmitted through thin needles directly into the lung tumor. The microwaves agitate water molecules in the cells, producing heat that destroys the cancer.

Cryoablation freezes the tumor instead of heating it. Hollow needles called cryoprobes are inserted into the tumor which then circulate extremely cold gases to freeze the cancer cells and form an ice ball, killing the malignant cells.

So while the energy sources differ, all these techniques cause cancer cell death by subjecting them to extremes of temperature - either very high heat through radiofrequency or microwaves, or freezing cold through cryoablation.

These minimally invasive procedures can be done percutaneously through the skin under image guidance rather than surgically opening the chest. This allows treatment of small peripheral lung tumors in patients who are not candidates for surgery due to other medical conditions.

Clinical Trials

Clinical trials allow patients to access new drugs or combinations that are still being studied but may provide benefit over standard care. For example, adding a new immunotherapy to chemotherapy for metastatic lung cancer may increase how long the treatment works compared to chemo alone.

Joining a trial gives patients a chance to receive cutting-edge targeted therapy matched to the specific mutations found in their tumor. Even for advanced lung cancer, clinical trials provide hope of trying the latest treatments.

Often a mix of therapies works better than just one alone. For early stage lung cancer, surgery followed by chemo prevents recurrence better than either treatment by itself. Or sometimes chemo plus radiation before surgery can shrink tumors to make them fully removable.

For advanced lung cancer, pairing immunotherapy with chemo boosts survival more than chemo alone. After that stops working, switching to another targeted drug based on new tumor testing extends survival further. Adding palliative radiation can ease any symptoms.

Throughout lung cancer treatment, other help like quitting smoking, pulmonary rehab, emotional support, nutrition and physical activity helps patients maintain strength to continue therapy.

The goal of multi-modality care is to use all proven treatments smartly in sequence or together when safest and most effective for each patient. Clinical trials expand options. The mix of therapies is tailored to each person's specific lung cancer situation.

Joining a clinical trial doesn't guarantee you'll actually be helped by the treatment being studied. The new drug or therapy might not turn out to be very effective, or could end up worse than standard care. Doctors really aren't sure until they test it on patients.

Experimental treatments often have unknown side effects or risks that could impact quality of life. Toxicities or complications might come up during the study that no one expected.

Being on a trial usually takes more of a patient's time with extra doctor visits, scans, and procedures to closely monitor how you're doing. There's a lot more than just taking a medication. It can disrupt family and work life.

Patients don't get to choose which treatment they get in a trial - it's randomly assigned by chance. So you may not get the one you hoped for. Some people just take a placebo or dummy pill too for comparison.

Insurance doesn't always cover unapproved treatments, so you might get sticker shock from high costs. And if the drug doesn't get FDA approval after the study, you won't be able to keep taking it even if it helps you.

While the chance to take the latest medicine not widely available yet sounds exciting, clinical trials come with a lot of uncertainty and strings attached. Learning the possible downsides can help patients make an informed choice whether the pros outweigh the cons for their situation.

The key is to use all safe and effective options through a dynamic treatment plan tailored to each patient's unique cancer characteristics and changing needs over time. A collaborative multidisciplinary team is essential to optimize and integrate the multi-pronged strategies. As you can see here, what we are presenting is the conventional approach to lung cancer. Later we will get to some of the adjunct approaches that are based in some of the other perspectives on how cancer is generated and how it functions. What we are trying to explain here is what you will encounter with most oncologists. We do this so that you can understand further what they are suggesting and why. We are always looking to increase your understanding so that you can make the best choices possible.

Photodynamic Therapy:

Photodynamic therapy uses a special type of sensitizing drug that accumulates in cancer cells and makes them sensitive to a particular wavelength of light. First, the photosensitizing agent is injected into the bloodstream and absorbed by cancer cells. Then, a laser light beam of the specific activating wavelength is focused on the tumor.

When the photosensitizer is hit with this light, it triggers a chemical reaction that creates a form of oxygen that is highly toxic to the cancer cells. This activated oxygen kills the cancer cells from the inside. The combination of photosensitizer and activating light come together for this targeted cancer cell killing effect.

However, the laser light only penetrates so far, so photodynamic therapy can only be used to treat very early stage lung cancers limited to superficial sites accessible by the light. It is generally used when the tumor is centralized in the airways rather than deeply within lung tissue. The light activation is done through a bronchoscopy procedure to reach the tumor.

Side effects include sensitivity to light and some pain or inflammation at the treatment site for a period of time. When feasible based on tumor location and size, photodynamic therapy provides an alternative locally-directed treatment option for early stage lung cancer without needing to remove part of the lung surgically.

Palliative therapies:

Palliative treatments are used when the cancer has spread extensively or recurred after initial treatment. The goal is no longer to try to cure the cancer, but to improve quality of life by managing symptoms from the disease.

For example, low dose palliative radiation can help shrink tumors pressing on bones, airways or the spinal cord to provide relief from pain, trouble breathing, or numbness/weakness. Radiation to the brain can alleviate neurological symptoms from brain metastases.

Palliative surgery like pleurodesis involves sticking the outside lining of the lungs to the chest wall to prevent fluid buildup that causes shortness of breath. Putting in a stent can open a blocked airway to make breathing easier.

The overall focus is on controlling symptoms and keeping the patient comfortable through procedures, medications, or other therapies - not necessarily eliminating every spot of cancer.

Supportive and palliative care, including help with physical symptoms, mental health support, and navigating difficult decisions, is a crucial part of the team approach throughout lung cancer treatment. Integrating it earlier on along with cancer-directed therapy provides the best quality of life. The goal is to minimize suffering from cancer and its effects, even when the underlying disease cannot be cured.

Prognosis for Lung Cancer

Here is a overview of the typical prognosis by stage for lung cancer and ways to help improve outcomes:

Stage I - The 5-year survival rate for stage I lung cancer is up to 92% for IA and up to 83% for IB. Complete surgical resection offers the best prognosis. Quitting smoking and adjuvant chemotherapy also improve survival.

Stage II - 5-year survival rates are 53-60% for stage IIA and 36-46% for IIB. Surgery plus chemotherapy with or without radiation therapy provides the best outcomes.

Stage III - 5-year survival for stage IIIA is 14-36% and for stage IIIB is 5-10%. Chemoradiotherapy with surgery if possible provides benefit. Newer immunotherapies as adjuvant treatment are improving survival.

Stage IV - The 5-year survival rate is less than 10% for metastatic disease. However, median survival is improving with newer targeted therapies and immunotherapies. Combination treatments tailored to genomics prolong progression-free survival.

Across all stages:

Quit smoking and get regular exercise, nutrition, sleep to optimize health.
Enroll in clinical trials for access to newest treatments.
Get genomic testing of tumor to match targeted therapies.
Consider palliative care early on for symptom management.
Resectable disease has better outcomes. Screening to catch early improves resectability.
Multimodality therapy improves survival compared to single treatments.

While lung cancer has a poor prognosis overall, survival for early stage is quite good with treatment. Metastatic disease prognosis is improving with new therapeutic options. Outlook is best when using all available treatments personalized to the biological specifics of each tumor.

History of Lung Cancer

Early History

Lung cancer was very rare prior to widespread tobacco use. Some cases were reported as early as 1761. Autopsies occasionally found lung tumors.
Primarily treated with surgery when identified. Pneumonectomy (lung removal) is sometimes performed but the prognosis is very poor.
Radiation therapy used experimentally in the early 1900s but results are mixed given limited imaging and radiation equipment.
No systemic treatments available. Most patients died within months of symptom onset. 5-year survival under 5%.

Late 20th Century

CT scanning enabled better lung imaging and staging from the 1970s.
Multi-modality approaches evolved using surgery, radiation, and chemotherapy together to improve outcomes.
Cisplatin found effective for lung cancer - improved survival when added to radiation.
Targeted therapies like gefitinib and erlotinib developed for EGFR and other mutations.

Mid-20th Century

Chest X-ray imaging advanced, allowing lung tumors to be detected earlier. Biopsies improved diagnosis.
Classification systems developed distinguishing small cell and non-small cell subtypes.
Surgery remained primary treatment for non-small cell cancer when operable. Exploration of chemotherapy and radiation combinations began.
Smoking is conclusively linked to lung cancer causation in 1950s-60s studies.

21st Century

Advances in minimally invasive surgical techniques - VATS lobectomy with quicker recovery.
Individualized chemotherapy and targeted therapy based on tumor molecular profiling.
Immunotherapies emerge as new treatment paradigm - checkpoint inhibitors particularly important.
Research identifying new driver mutations and resistance mechanisms continues guiding drug development.
5-year survival now up to around 25% from very poor historical rates, but still more progress needed.

In summary, understanding of lung cancer biology together with advances in surgery, imaging, chemotherapy, targeted therapy, and immunotherapy have progressively improved the prognosis, though it remains a very deadly disease requiring ongoing research.

Overview of the different types of lung cancer and how they are differentiated:

Lung cancer is first divided into two major buckets - small cell and non-small cell. Non-small cell cancer is much more common, making up about 85% of cases. It's named that way because of how the cancer cells look under the microscope - they are larger than small cell cancer cells.

Non-small cell lung cancer includes adenocarcinoma, squamous cell, and large cell carcinoma. Adeno is usually found in the outer parts of the lung and is the most common type in nonsmokers. Squamous cells tend to be linked to smoking and are in the center airways. Large cells can be anywhere and grow fast. Doctors can usually tell them apart by staining samples from a tumor biopsy and seeing the shapes and features of cells.

Small cell lung cancer is almost always caused by smoking and starts in the larger bronchi in the central chest area. It grows and spreads quickly. Under the microscope, the cells are very small and round, different than non-small cell cancer cells. It also has some different biomarkers.

Other much less common lung cancers like carcinoid tumors and sarcomas occur, but doctors can identify them through biopsy by their unique microscopic appearance and markers.

The stage of any lung cancer - meaning how far it has spread in the body - is very important for figuring out treatment. Early stage has a better outlook than late stage or metastatic lung cancer. Doctors determine the stage with imaging tests and sometimes surgery.

For non-small cell lung cancer, doctors also do molecular testing on biopsy samples to look for mutations in genes like EGFR that can be targeted with specific medicines. This personalized information helps guide treatment.

So in more plain terms, lung cancer is a broad term for many subtypes, but doctors categorize them based on cell features and biomarkers to select the appropriate therapy.

Differentiation

Doctors determine which type of lung cancer someone has by examining the tumor cells under a microscope. They also do special stains on the biopsy samples to detect certain proteins on the cells.

For small cell lung cancer, the cells are very small and oval-shaped under the microscope. Staining shows they contain granules typical of neuroendocrine cells.

Adenocarcinoma cells are shaped like goblets and stain positive for proteins like TTF-1 and Napsin A. This indicates they started from glands that make mucus.

Squamous cell carcinoma originates from the flat, scale-like squamous cells that line the airways. These cancer cells stain positive for proteins like p40 and CK5/6.

Large cell carcinoma is named that way because under the microscope, the cancer cells just look abnormally large. The tumors don't have the shapes and markers of small cell, adenocarcinoma, or squamous cell types.

Carcinoid tumors contain uniform-looking, polygonal cells that stain positive for neuroendocrine proteins like chromogranin and synaptophysin.

In addition to examining cells under the microscope, doctors test for certain genetic mutations that can guide targeted therapy options, especially for non-small cell lung cancer.

The stage of the cancer still guides overall prognosis and primary treatment approach. But differentiating the specific cell type through morphology and staining provides crucial information to select the most appropriate therapies.