Bronchial Adenoma.

 

Bronchial Adenoma

PKGhatak,MD

Bronchial adenomas are mostly benign, but some adenomas have malignant potential and still, others are low grade malignant. Bronchial adenoma arises underneath the surface layer of the mid-sized bronchus of the lower lobes of the lungs. In rare cases, adenoma originates in the peripheral bronchus. An adenoma is the second most frequent primary tumor of the lung and accounts for 5 to 15 % of all primary pulmonary tumors. Adults between 30 and 40, with or without a smoking history, develop adenoma. Incidence in females is higher. It is a slow growing tumor and can be confused with cancer of the lung because of frequent and sudden onset hemoptysis or patients present with recurrent pneumonia of the same lobe of the lung indicating bronchial obstruction.

The tumors arise from the mucous gland or duct of the mucous gland. The tumor is small and the surface is covered with tiny blood vessels and appears red or fleshy pink when visualized during bronchoscopy, and manipulation of the tumor produces profuse bleeding. In 80% of cases, the adenomas grow with a wide base and grow towards the lumen and at times a filamentous adenoma may be found hanging in the lumen. Adenoma also grows towards the outer walls but less frequently.

Pathological types.

The adenomas are classified as Cylindroma and Carcinoid. Cylindromas are then subclassified as adrenocystic and mucoepidermoid adenomas.

Adenocytic adenoma arises from the cells of the mucus glands of the bronchus. This tumor behaves like a salivary gland tumor. Mucoepidermoids are essentially benign tumors located in the main bronchus and trachea. Structurally these tumors vary from cystic to solid and contain not only mucus producing cells but also other cell types.

Pulmonary carcinoid adenomas are no different from carcinoid tumors originating elsewhere. Carcinoids account for 80% of primary lung tumors. They arise from the Kulchitsky cells acquired during embryonic development. Bronchial carcinoids secrete serotonin and blood levels of serotonin remain high in the upper portion of the body. The high blood level of serotonin produces flushing of the face, increased tearing, redness of the chest wall, wheezing, fall of BP and tachycardia, and right ventricular valvular abnormalities. Bronchial carcinoid was discussed in greater detail in an earlier blog titled “Carcinoid and other neuroendocrine tumors”. Carcinoid tumors produce paraneoplastic syndrome by secreting various hormones - ACTH, ADH, Insulin like growth hormones. Occasionally, one carcinoid adenoma secretes multiple hormones. Carcinoid tumors are characterized by uniform closely packed clusters of polygonal to small cells.

Symptoms of bronchial adenoma.

The symptom begins with an unproductive cough, specially, when a patient is recumbent in bed or assumes a particular position. And the cough stops after changing position. Recurrent bouts of respiratory infections and pneumonia of the same lobe of the lung are the second most presentation. Hemoptysis is common and occurs suddenly without any warning. However, hemoptysis stops spontaneously.

Chest pain, wheezing and shortness of breath are less frequent and mostly depend on the degree of bronchial obstruction.

Behavior of bronchial adenoma.

Pathological examination of bronchial carcinoids will not differentiate benign from malignant; the biological behavior of the carcinoid tumor, in time, reveals the true nature of the tumor. Only about 4 % of carcinoids are malignant and peripherally located and are more likely to be malignant.

Adenocystic adenoma behaves as a low-grade malignant tumor, spreads locally underneath the cell surface. It is difficult to know the extension of the tumor spread pre-operatively.

The centrally located mucoepidermoid is benign.

Diagnosis.

The nature of the presenting symptoms requires a prompt bronchoscopy. The tumor location, visual identification and biopsy are attempted in all cases. But since the tumors are small, tumors may not be identified in every case.

The plain chest x-ray may not show the tumor but the secondary pulmonary changes due to the bronchial obstruction – atelectasis, pneumonia, bronchiectasis and various combination of these are detected by chest x-rays. CT scans are more sensitive and detect adenoma in larger airways, but may fail to locate the really small tumors.

PET scans may miss the adenomas because of their low level of metabolic activities.

Octreotide scan for carcinoid was discussed in an earlier blog.

Biopsy.

The tissue diagnosis of cylindroma is performed by the usual staining of slides. Immunohistological staining is generally required for carcinoid tumors.

Treatment.

All bronchial tumors are removed by surgery whenever it is possible. Often, a lobe of the lung is required to be removed because of permanent pathological changes. Radiation therapy is an appropriate modality in the treatment of adenocystic tumors.

Prognosis.

The prognosis is very favorable for cylindromas. In carcinoid tumors, continued surveillance is necessary because of the unpredictable behavior of the tumor and specially the malignant carcinoid which metastasized to the liver early.

 

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Understanding Chronic Bronchitis

 

Understanding Chronic Bronchitis

PKGhatak,MD

Chronic bronchitis is hardly discussed as such nowadays, it is currently grouped together with pulmonary emphysema and is known as chronic obstructive pulmonary disease.

Shortly after the first World War one, cigarette smoking became a socially cool thing and spread quickly worldwide. It did not take long before doctors in England noticed a sharp increase in chronic cough and sputum production in cigarette smokers. Doll and Hill published their landmark research paper in 1969 on the adverse effects of cigarette smoking and demonstrated the direct correlation between the number of cigarettes smoked with the incidence of lung cancer. Pathologists reported gradual changes of the respiratory epithelium of the bronchial tree to the squamous epithelium and an increase in the proliferation of mucus producing cells, Goblet cells, in smokers. Subsequently, the further transformation of squamous cells to cancer cells was demonstrated. Even then, Chronic bronchitis continued to increase and became a very common malady of that time.

It did not take long to notice that non-smokers were having chronic bronchitis too. Secondhand smoking, a new term, was coined; subsequently, coal burning smoke from factories, at home coke or firewood burning stove fumes were linked to chronic bronchitis. It is now accepted that repeated exposures to noxious fumes, like chlorine, ammonia, etc. lead to the development of chronic bronchitis in both non-smokers and smokers.

Inhaled air travels in a laminar flow down the tracheobronchial tree to the alveoli of the lungs. Because of the changed respiratory epithelium and increased goblet cells, the airflow becomes eddy flow at points of irregularities of the surface. The flow rate decreases in proportion to the irregular surface area. During inspiration, in a normal lung, the airway elongates and narrows. The combined effects, of surface changes and changes in the caliber of airways during inspiration, result in decreased air entry in the lungs. During expiration the electric recoil of the lung and the chest wall, is the sole force, to push air out of the lungs. The force generated by the elastic tissue is directly proportional to the stretched length of elastic fibers. As lungs are less inflated during inspiration, the air low during expiration is reduced. In clinical practice, decreased airflow during expiration is utilized to categorize the degree of severity of chronic bronchitis and is also used as a reliable tool for monitoring the effects of medical therapy. The test is quickly learned by the patients and the gadget costs only a few dollars and is covered by insurance. The test is called Air Flow Meter.

Behind the scenes in the Lab.

In an earlier time, learning Inflammation and infection was not difficult. With the knowledge of the immunity - innate and adaptive, the role of individual subsets of immunocytes, the importance of cell to cell communication, powerful enzymatic actions of cytokines, bradykinins, chemokines, the role of prostaglandins, interleukins, cellar growth promoting factors, vascular endothelial growth factor, etc. and the role, of the master programmer, the genes and messenger RNA, if not complicated enough, then add gene mutation, age related Telomere gene deletion, point mutations, etc. made medical study akin to study FBI agents receive at the academy.

That aspect is voluminous and better studied under the heading of inflammation, repair and remodeling. In the study of chronic bronchitis, there is no way out other than, at the minimum, to mention some of the processes at critical points of symptom development.

Age and lung function.

At birth, the lung structure and maturity cells are not fully developed. Lungs continue to grow and cells mature during childhood. Lung growth accelerates during adolescence. By the time the longitudinal growth of the long bone ceases, the lungs also stop growing. The lung is an exceptional organ because it begins to lose function after mid 20s. It is estimated that an individual loses 1 % of lung reserve each year. Until the loss of volume is greater than 50%, the patients remain asymptomatic. In cigarette smokers, the rate of decline of lung functions is much faster, and they become symptomatic earlier.

In addition, the changes in genes due to age manifest in a variety of ways. Every chromosome has several genes, and each gene has a beginning and end part. The end part of the gene is called Telomere. In advanced age, the telomere portion of the gene is lost. Depending on the gene function, the symptoms vary. Telomere deletion leads to decreased immune functions, specially the repair and remodeling of the lungs.

Symptoms and progression of chronic bronchitis.

Patients become symptomatic after considerable lung damage. Some inhaled chemicals are direct toxins to respiratory cells or due to the generation of free radicals at the local level. Some inherited conditions, like alpha1 antitrypsin deficiency, dyskinesia of ciliary epithelium of the respiratory tract, congenital mitochondrial diseases and macrophage enzyme deficiency, accelerate these changes.

Cough and increased mucoid mucus production are mostly observed in the morning after waking up. Later, more frequent symptoms are noticed during the evening and night. At this stage, the chest x-ray may be negative, but the vital capacity is reduced and also FEV1(expired air volume in the 1^st second of expiration). Similarly, the flow rate is reduced. Frequent respiratory infections due to respiratory viruses are common and occasional bacterial infections are seen.

Each new episode of viral, bacterial infection or exposure to toxins produces destruction of the lamina propria, smooth muscles and elastic fibers.

Repair and remodeling do not progress normally because of repeated inflammations. Haphazard laying down of new cells, generated by the resident progenitor cells of the endothelium, fibroblasts, and myeloblasts produce irregular remodeling and more obstruction to airflow. Bronchioles less than 2 mm in diameter show a 40 to 50 % reduction of the caliber and can be demonstrated by HTCT (high regulation CT). Loss of elastic fibers distorts the delicate alveoli and capillaries. The surface area of the alveoli is reduced. A mismatch between ventilation and circulation occurs. The arterial oxygen saturation falls during exercise and later at rest. Continuation of infections, abnormal repairs and remodeling produce hypoventilation and Carbon dioxide retention. After each bout of infections,  patients experience progressively worsening shortness of breath.

Chest x-ray shows heavy bronchovascular markings and is in association with patches of infiltrates. Hyperinflation of sub-segmental lobes, most marked in the upper zone of the lungs is seen. Still later, the radiological picture becomes a combination of chronic bronchitis and emphysema. The progression of the disease takes several years. It is not unusual that patients to live with chronic bronchitis for 40 to 50 years. At the final stage, the pulmonary arterial pressure increases in a step-wise fashion in line with the damage to the lung. Right ventricular hypertrophy develops as a compensatory mechanism, and later right heart fails to keep up and congestive heart failure develops.

 

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Mycobacterium avium-intercellulare

 

Mycobacterium avium- intracellulare complex

PKGhatak,MD

Mycobacterium avium-intracellulare complex (MAC) is a combination of two species of Non-Mycobacterium tuberculosis (NMB). In the past, other NMB species were lumped into this complex.

MAC bacteria exhibit characteristics so very similar and produce almost identical human diseases that the diseases cannot be differentiated clinically and only by the use of genome probe tests actual species diagnosis is made with ease.

MAC is ubiquitous in nature, many MACs are present in water, soil, house dust, plumbing, tap water, etc. Both healthy and immunosuppressed people carry MAC in the respiratory and GI tracts and produce no inflammation or diseases. In fact, it is not easy to establish a pulmonary disease due to MAC unless tissue invasion and recovery of MAC are demonstrable in the biopsy tissues. Person-to-person transmission does not happen.

People with immunosuppression are living longer and the incidence of MAC infection is rising. HIV infected patients, until recent years, were devastated by MAC and are still susceptible to M.avium infection. Elderly women are particularly susceptible to M.intercellulare. The actual reason for their susceptibility is not known. It was thought that modesty in earlier English women prevented them to cough in public resulted in retaining sputum in the airways and that was responsible for repeated infections and the development of nodular bronchiectasis. This is known as Lady Windermere syndrome.

In a rare instances, multiple family members develop cervical lymphadenitis by MAC due to congenital deficiency of IFN-y receptor expression or the gene. Patients with gastroesophageal reflux, gastric acid suppression by medications and gastric aspirations are susceptible to M.intercellulare pulmonary infection. Globally MAC is a major problem in poor nations where MTB is common and often MAC are misdiagnosed as drug resistant MTB. In France, New Zealand, and the U.K. MAC incidence is increasing.

Manifestations of MAC infection.

The clinical picture is better described under immunocompetent and in immunosuppressed populations.

In immunocompetent people.

These manifestations are encountered – Cavitary pulmonary infection, Nodal bronchiectasis and Hypersensitive pneumonitis. And cervical lymphadenitis in children.

Cavitary pulmonary infection.

The clinical picture of this entity is similar to M.kansasii infection. The only way to differentiate between the two is to use a newer species identification test like a genome probe test.

Similarly, the clinical pictures of nodular bronchiectasis and hypersensitive pneumonitis are similar to M.kansasii infection.

MAC can infect children. Cervical lymph nodes are commonly infected. In a rare instances, other lymph nodes in the axilla, hila of lungs and groin are infected.

Extrapulmonary MAC infection sites are flat bones, breasts, bone marrow, skin, muscles, brain, and GI tract in immunosuppressed people.

Pulmonary manifestations of MAC.

In immune competent.

Cavitary pneumonia, nodular bronchiectasis, hypersensitive pneumonitis.

In children with cervical lymph nodes.

In immunosuppressed people.

Multi-organ infections besides lungs are bone marrow, spleen, retroperitoneal lymph nodes, kidneys, liver and occasionally brain and meninges.

Diagnosis of MAC.

Chest Radiographs.

The chest x-ray is not sensitive enough to an early diagnosis of MAC. High -resolution-CT scan (HRCT) shows the lesions much more clearly. Fibro-cavitary changes in the upper lung zones. In elderly women fibronodular bronchiectasis and nodules in the right middle lobe. In addition, atelectasis, consolidation, ground-glass opacities on CT appear as a tree in early spring with the emerging buds – Tree-Bud appearance. In hypersensitive pneumonitis, centrilobular nodules, ground-glass opacities, and hyperinflation coalesced alveoli due to trapped air during expiration indicating expiatory bronchial obstruction.

In HIV patients abdominal CT reveals retroperitoneal and periaortic lymphadenitis, enlarged spleen, and liver.

Biopsy.

Infected tissues are biopsied by a method suitable to patients in order to minimize tissue damage by the biopsy process. Commonly bronchoscopic transbronchial lung biopsy is practiced. Other methods are CT-guided needle biopsy, Transthoracic video assisted tissue biopsy and open lung biopsy.

Culture for MAC.

Blood, urine, pus, lung tissue, node biopsy, bone marrow, and liver biopsy tissues are stained by Ziel Nielsen stain for Acid-fast bacteria (AFB) and cultured in rapid growing culture media.

In tissues with only a few AFB Nuclear, acid amplification tests followed by genome probe tests are done.

Histology.

In HIV positive cases inflammatory nodes are few, but AFB is plentiful and appears as sheets of macrophages loaded with AFB.

Cervical lymph nodes.

Both caseating and non-caseating granuloma with sinuous tracts of eosinophilic necrosis and scatted nuclear debris are present. Langhans giant cells surrounding nodules are easily identified and neutrophils are rare and lymphocytes are few. AFB is present in a few numbers.

In immunocompetent patients.

Typical non-caseating granuloma and significant numbers of AFB are present.

Treatment.

Drugs used in Pulmonary tuberculosis (MTB) are generally resistant in MAC cases.

Macrolides are the mainstay of therapy, at minimum three drugs are prescribed for 12 months. The usual protocol includes macrolides. rifamycin and ethambutol. Other drugs with variable effectiveness are clofozinidine, fluoroquinolones, aminoglycosides, and inhaled liposomal amikacin.

Various combinations of drugs are used based on the sensitivity test results and response noted in a patient. From treatment centers to nurses- observed intermittent therapy is used to maximize effectiveness and compliance.

Surgery.

Cervical lymphadenitis is best treated with surgical excision. In general drug treatment is not required.

In resistant pulmonary MAC, lobectomy may be required, in addition to a maximum tolerable dose of drugs.

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