NEET MDS Lessons
General Pathology
Neuroblastoma and Related Neoplasms
Neuroblastoma is the second most common solid malignancy of childhood after brain tumors, accounting for up to10% of all pediatric neoplasms. They are most common during the first 5 years of life. Neuroblastomas may occur anywhere along the sympathetic nervous system and occasionally within the brain. Most neuroblastomas are sporadic. Spontaneous regression and spontaneous- or therapy-induced maturation are their unique features.
Gross features
- The adrenal medulla is the commonest site of neuroblastomas. The remainder occur along the sympathetic chain, mostly in the paravertebral region of the abdomen and posterior mediastinum.
- They range in size from minute nodules to large masses weighing more than 1 kg.
- Some tumors are delineated by a fibrous pseudo-capsule, but others invade surrounding structures, including the kidneys, renal vein, vena cava, and the aorta.
- Sectioning shows soft, gray-tan, brain-like tissue. Areas of necrosis, cystic softening, and hemorrhage may be present in large tumors.
Microscopic features
- Neuroblastomas are composed of small, primitive-appearing neuroblasts with dark nuclei & scant cytoplasm, g rowing in solid sheets.
- The background consists of light pinkish fibrillary material corresponding to neuritic processes of the primitive cells.
- Typically, rosettes can be found in which the tumor cells are concentrically arranged about a central space filled with the fibrillary neurites.
- Supporting features include include immunochemical detection of neuron-specific enolase and ultrastructural demonstration of small, membrane-bound, cytoplasmic catecholamine-containing secretory granules.
- Some neoplasms show signs of maturation, either spontaneous or therapy-induced. Larger ganglion-like cells having more abundant cytoplasm with large vesicular nuclei and prominent nucleoli may be found in tumors admixed with primitive neuroblasts (ganglioneuroblastoma). Further maturation leads to tumors containing many mature ganglion-like cells in the absence of residual neuroblasts (ganglioneuroma).
Many factors influence prognosis, but the most important are the stage of the tumor and the age of the patient. Children below 1 year of age have a much more favorable outlook than do older children at a comparable stage of disease.
Miscroscopic features are also an independent prognostic factor; evidence of gangliocytic differentiation is indicative of a "favorable" histology. Amplification of the MYCN oncogene in neuroblastomas is a molecular event that has profound impact on prognosis. The greater the number of copies, the worse is the prognosis. MYCN amplification is currently the most important genetic abnormality used in risk stratification of neuroblastic tumors.
About 90% of neuroblastomas produce catecholamines (as pheochromocytomas), which are an important diagnostic feature (i.e., elevated blood levels of catecholamines and elevated urine levels of catecholamine metabolites such as vanillylmandelic acid [VMA] and homovanillic acid [HVA]).
Nevus
1. Commonly known as moles.
2. A benign, pigmented tumor of melanocytes, found deep within connective tissue.
3. Types of skin nevi:
a. Junctional nevus—found in the epidermis.
It is the only type of nevus that may be considered to be premalignant.
b. Compound nevus—found in both the epidermis and underlying dermis.
c. Intraepidermal nevus—found in the dermis.
Nephrotic Syndrome
The patient will present with a triad of symptoms:
- Proteinuria, i.e. >3g/24hr-3.5g/24 hr
- Hypoalbuminaemia, i.e. <30g/L
- Oedema
>80% of cases are due to glomerulonephritis. In this syndrome, there is damage to podocytes
Clinical signs
- Pitting oedema, particularly in the limbs and around the eyes; may also cause genital oedema and ascites.
- Possible hypertension
Causes
- Primary causes – these are diagnoses of exclusion that are only made if secondary causes cannot be found
o Minimal change disease (MCD)
o Focal segmental glomerulosclerosis
o Membranous nephropathy
- Secondary causes – note that these fall into the same three categories as above:
o Minimal change disease – Hep B, SLE, diabetes M, sarcoidosis, syphilis, malignancy
o Focal segmental glomerulosclerosis –HIV, obesity, diabetes M, hypertensive nephrosclerosis
o Minimal change disease –drugs, malignancy, particularly Hodgkin’s lymphoma
- Differential diagnoses include cardiac failure, i.e. increased JVP, pulmonary oedema and mild proteinuria, and liver disease, i.e. reduced serum albumin.
- The condition causes an increased susceptibility to infection – partly due to loss of immunoglobulin in the urine. Patients tend to be prone to streptococcus infection, as well as bacterial peritonitis and cellulitis.
- Nephrotic syndrome also increases the risk of thromboembolism and hyperlipidaemia.
- The former is due to an increase in the synthesis of clotting factors and to platelet abnormalities, and the latter is a result of increased synthesis of these by the liver to counteract reduced oncotic pressure.
Investigations
- These are the same as those carried out in GN.
- Also, check for cholesterol as part of confirming the presence of hyperlipidemia.
- Renal biopsy – order this for all adults. In children, because the main cause is minimal change GN, steroids are the first-line treatment. Therefore, in children, biopsy is necessary only if pharmaceutical intervention fails to improve the situation.
- The hypercoagulant state seen in the nephrotic syndrome can be a risk factor for renal vein thrombosis. This can present as loin pain, haematuria, palpable kidney and sudden deterioration in kidney function. This should be investigated with Doppler USS, MRI or even renal angiography.
- Once diagnosed, give warfarin for 3 to 6 months.
Management
- Generally, this involves treatment of the underlying condition which is usually GN. Therefore, fluid management and salt intake restriction are priorities. The patient is usually given furosemide along with an ACE inhibitor and/or an angiotensin II receptor antagonist. Prophylactic heparin is given if the patient is immobile. Hyperlipidaemia can be treated with a statin.
Nephritic Syndrome
Acute and chronic
forms of the syndrome exist. The main difference between this and nephrotic syndrome is that in nephritic syndrome haematuria is present. There is also proteinuria, hypertension, uraemia, and possibly oliguria. The two standout features are hypertension and RBC casts. The urine will often appear ‘smoky’ in colour due to the presence of RBC casts. Very rarely, it may appear red
Causes
1. Post-streptococcal
2. Primary:
- Membranous glomerulonephritis
- Rapidly progressive glomerulonephritis
- IgA nephropathy (Berger’s disease)
3. Secondary
- HSP
- Vasculitis
Clinical Features
- Abrupt onset of :
o Glomerular haematuria (RBC casts or dysmorphic RBC)
o Non-nephrotic range proteinuria (< 2 g in 24 hrs)
o Oedema (periorbital, sacral )
o Hypertension
o Transient renal impairment (oliguria, uraemia)
- Urinary casts – these are cylindrical structures produced by the kidney and present in the urine in certain renal diseases. They form in the DCT and collecting duct, dislodging and passing in the urine where they are detected by microscopy. RBC casts are usually associated with nephritic syndrome. The presence of RBCs within a cast is always pathologic and strongly indicative of glomerular damage.
- The proteinuria present is often smaller than in nephrotic syndrome, thus a coexistent condition of nephrotic syndrome is not usually present.
- Encepelopathy may be present, particularly in children, due to electrolyte imbalances and hypertension. This type of presentation is indicative of glomerular damage, but requires renal biopsy to determine the exact problem. In this respect it is similar to nephrotic syndrome.
Overlapping of the two syndromes is possible as nephrotic syndrome may precede nephritic syndrome, although not vice-versa.
Mechanisms of the syndrome vary according to cause; both primary and secondary causes exist. Post-infectious GN is the classic illustration of nephritic syndrome, but the condition may be caused by other glomerulopathies and by systemic diseases such as connective tissue disorders
Two clinical terms to remember:
- Nephritic syndrome; which comprises edema, proteinuria, hypoalbuminemia, hematuria (smoky urine), oligurua and hypertension.
- Nephrotic syndrome; which comprises of albuminuria, hypoalbuminemia, edema, hyperlipidemia, lipiduria.
1. Pyogenic liver abscesses may be caused by E. coli, Klebsiella, Streptococcus, Staphylococcus, Bacteroides, Pseudomonas, and fungi.
Parasitic infections
1. Schistosomiasis is caused by different organisms in different parts of the world.
a. Clinical features include splenomegaly, portal hypertension, and ascites. Lesions are caused by the immune response to ova.
2. Amebiasis is caused by Entamoeba histolytica.
a. Clinical features include bloody diarrhea, pain, fever, jaundice, and hepatomegaly.
Drug-induced liver damage may be caused by agents that are direct hepatotoxins, such as carbon tetrachloride, acetaminophen, methotrexate, anabolic steroids, and oral contraceptive pills.
Pneumoconioses—are environmentally related lung diseases that result from chronic inhalation of various substances.
1. Silicosis (stone mason’s disease)
a. Inhalant: silica dust.
b. Associated with extensive fibrosis of the lungs.
c. Patients have a higher susceptibility to tuberculosis infections.
2. Asbestosis
a. Inhalant: asbestos fibers.
b. Associated with the presence of pleural plaques.
c. Consequences include:
(1) Mesothelioma (malignant mesothelial tumor).
(2) Bronchogenic carcinoma.
3. Anthracosis
a. Inhalant: carbon dust.
b. Usually not as harmful as silicosis or asbestosis.
c. Associated with the presence of macrophages containing carbon.