When a hamartoma is suspected in an individual, determining whether a mass is benign or malignant based solely on its anatomical location is a major error in judgment. Anatomical location has no predictability on the malignant potential of a certain lesions. Most hamartomas are found as an asymptomatic nodule on a routine plain x-ray, which then leads to further work up. During the patient’s history, one should ask about any smoking history, exposure to chemicals, previous malignant tumor, recent travel and type of work.

The majority of hamartomas are discovered incidentally when working up a patient for another disorder. Sometimes the patient may report a mass and in other cases, the mass may be seen on an x-ray or CT scan. However, depending on where the hamartoma is located, some symptoms may arise and include the following:

• Hemorrhage
• Infection
• Ischemia or infarction of tissues
• Mass of varying size
• Pain which may be dull or aching
• Pressure like sensation
• Low grade fever
• Pathological fracture
• Spinal cord compression
• Paresthesias
• Bursitis
• Unequal limb lengths
• Varus or valgus deformity

Other symptoms may depend on which organ they occur. For example lung hamartomas are usually asymptomatic but may present with cough, hemoptysis, wheezing, pneumonia or chest pain.

• Asymptomatic

  Albeit usually asymptomatic and rare in children, when it occurs in the pediatric population it is more commonly symptomatic. [ncbi.nlm.nih.gov]

  Most are asymptomatic, but they can cause dyspepsia or upper gastrointestinal bleeding.Hamartomas of the spleen are uncommon but can be dangerous. [en.wikipedia.org]

  Most patients are asymptomatic and the diagnosis is incidental. Patients may have an overlying skin lesion/defect. Key Diagnostic Features: Spinal hamartomas are usually asymptomatic and are easily differentiated from other lesions with MRI. [ajnr.org]

• Precocious Puberty

  Clinically, most patients with hypothalamic hamartomas present with precocious puberty and/or gelastic epilepsy. We report an interesting case of hypothalamic hamartoma causing precocious puberty in a young male. [karger.com]

  K. and Bebin, J.: Posterior hypothalamus hamartomas and gangliogliomas causing precocious puberty. Neurology Minneap., 8: 164-174, 1958. 46. Loop, J. W.: Precocious puberty. [jpgmonline.com]

  Hamartomas attached anteriorly in the region of the tuber cinereum cause central precocious puberty. Larger lesions with anterior and posterior attachment cause both seizures and central precocious puberty. [epilepsydiagnosis.org]

  Two clinical phenotypes of HH are recognized: 1) central precocious puberty and 2) epilepsy and related neurobehavioral symptoms. For those with central precocious puberty only, symptoms may occur as early as 1-3 years of age. [rarediseases.org]

• Pallister-Hall Syndrome

  Causes Sporadic (95%) Pallister-Hall syndrome (5%) PALLISTER HALL SYNDROME This syndrome includes polydactyly, a bifid epiglottis, dysplastic nails, imperforate anus, kidney abnormalities and hypothalamic hamartoma. [epilepsydiagnosis.org]

  Pallister-Hall syndrome (PHS) is a rare malformative disorder that is due to truncating functional repressor mutations in GLI3. Since the seminal publication in 1980, hypothalamic tumors have been recognized to be a cardinal feature of PHS. [ncbi.nlm.nih.gov]

  Pallister-Hall syndrome, for example, is a genetic condition that can present with deformities of the hands and feet and other anatomical anomalies, including hypothalamic hamartoma. [chop.edu]

  […] seizure types, such as absence, atonic, tonic, or tonic-clonic Cognitive problems, such as changes in thinking, memory, attention ) Sudden episodes of rage (called hypothamaic rages) Other types of changes in mood or behavior Precocious or early puberty Pallister-Hall [epilepsy.com]

  Congenital HH are found as part of Pallister-Hall syndrome. Uterine fibroids are a common hamartoma. Prevalence Depends on organ and inherited predisposition Biliary hamartomas (von Meyenburg complexes) were found in 0.6% of liver biopsies. [unboundmedicine.com]

• Short Stature

  stature ( Aarskog-Scott syndrome, Cockayne syndrome, Cornelia de Lange Syndrome, Dubowitz syndrome, Noonan syndrome, Robinow syndrome, Silver-Russell dwarfism, Seckel syndrome, Smith-Lemli-Opitz syndrome ) limbs ( Adducted thumb syndrome, Holt-Oram syndrome [wikidoc.org]

  stature. [34], [37] Cyproterone acetate has been effective in delaying sexual changes and has question able effect on skeletal growth. [jpgmonline.com]

  The health consequences of abnormally early puberty include short stature and problems with age-appropriate psychosocial adjustment. [rarediseases.org]

  Osteochondroma is caused by herniation of the epiphyseal cartilage through a developmental defect in the epiphyseal plate. [4] Multiple osteochondromas, also known as hereditary multiple cartilaginous exostoses, are usually associated with short stature [emedicine.medscape.com]

• Malaise

  We report our fluorine-18-fluorodeoxyglucose positron emission tomography/computed tomography (18FFDG PET/CT) findings in a 51 years old female presenting with B symptoms, respectively fever, night sweats and malaise, that underwent an 18F-FDG PET/CT [ncbi.nlm.nih.gov]

  […] producing small wheals spaced 1.5 to 2.0 cm apart. 17 Complications are scarce and may include local weakness, injection site reactions (eg, pain, edema, erythema, ecchymosis, hyperesthesia), generalized idiosyncratic reactions (eg, nausea, fatigue, malaise [jamanetwork.com]

• Sputum

  […] cytology: This procedure involves the collection of mucus (sputum), coughed-up by a patient, which is then examined in a laboratory by a pathologist. [dovemed.com]

  Sputum smears for acid fast bacilli were negative and cytology of sputum and bronchial washings revealed no malignant cells. On pulmonary function test, FVC was 2.64 L (108% of predicted value), FEV 1 1.24 L, (71% of predicted value) FEV 1 /FVC 74%. [kjim.org]

  Sputum for acid fast bacilli was negative. His chest x-ray showed a dense homogeneous opacity in the right upper zone consistent with collapse/consolidation ( Figure 1 ). [omicsonline.org]

• Loss of Appetite

  Loss of appetite Pain in abdomen Blood in the stool or changes in bowel habits Aches, pains, lumps or swelling that cannot be explained Headaches or changes in vision or nerve function that do not go away It is important to seek medical help if anything [stjude.org]

• Visual Impairment

  A combined hamartoma can cause visual impairment in several ways, but vision loss most commonly occurs when retinal dragging causes foveal distortion [ 11, 14, 21 ]. [journalretinavitreous.biomedcentral.com]

• Visual Impairment

  A combined hamartoma can cause visual impairment in several ways, but vision loss most commonly occurs when retinal dragging causes foveal distortion [ 11, 14, 21 ]. [journalretinavitreous.biomedcentral.com]

• Papule

  We report a case of a slowly growing papule on the nasal bridge of an elderly woman. [ncbi.nlm.nih.gov]

  Affected individuals usually have macrocephaly, trichilemmomas, and papillomatous papules, and present by the late 20s. The lifetime risk of developing breast cancer is 85%, with an average age of diagnosis between 38 and 46 years. [snpedia.com]

  Affected individuals have macrocephaly and almost all will develop the pathognomonic mucocutaneous lesions by the third decade of life, including trichilemmomas, papillomatous papules, and acral and plantar keratoses. [genedx.com]

  A, Trichilemmoma; B, Papillomatous papules. White arrows denote the more prominent papillomatous papules. Individuals with CS are at increased risk for the development of benign and malignant tumors of breast, thyroid, and endometrium. [nature.com]

  The child may show bouts of extreme rages, poor social adjustment and often precocious puberty. [ 10 ] Signs Skin and mucous membranes Papules of various types, fibromas, keratoses, café-au-lait patches and haemangiomas are all described. [patient.info]

• Skin Papule

  hands, legs, feet) Papillomatous skin papules – wart-like lesions which can appear anywhere, with feet and hands commonly being affected Mucosal papillomas – Benign overgrowth of tissue affecting the tongue, gums, or inside the nose Trichilemmomas – [snpedia.com]

  hands, legs, feet) ·Papillomatous skin papules – wart-like lesions which can appear anywhere, with feet and hands commonly being affected ·Mucosal papillomas – Benign overgrowth of tissue affecting the tongue, gums, or inside the nose ·Trichilemmomas [rarediseases.org]

  Similar to the CS/BRRS phenotype, rare individuals with BHD may present with trichilemmomas, lipomas, and skin papules; however, the disorder is genetically distinct from the PHTS, as pathogenic mutations have been identified in BHD/FLCN. [nature.com]

• Irritability

  This study is one of the few reports of this rare clinical entity causing irritative voiding symptoms and constipation in a male patient. [ncbi.nlm.nih.gov]

  Some lesions represent developmental malformations, whereas others may be reactive lesions, after trauma or chronic irritation. [doi.org]

  If located endobronchially, they can cause irritation of bronchial mucosa resulting in persistent cough as a presenting symptom. [emedicine.com]

  […] múltiple A02 Escalofríos A03 Fiebre A04 Astenia/cansancio/debilidad A05 Sensación de enfermedad A06 Desmayo/síncope A07 Coma A08 Inflamación A09 Problemas de sudoración A10 Sangrado/hemorragia NE A11 Dolor torácico NE A13 Miedo al tratamiento A16 Lactante irritable [iqb.es]

• Stroke

  These include hydrocephalus, stroke and death. [my.clevelandclinic.org]

  But in general, if surgical treatment has been chosen, meticulous planning must be done due to the risks that include infection, bleeding, hydrocephalus, stroke, and death. [abc.go.com]

• Hyperactivity

  Trichilemmomas (benign skin lesions) Papillomatous papules (small flesh-colored nodules in the skin or mouth) Lipomas (fatty nodules under the skin) Thickened skin of the hands and feet (acral and plantar keratosis) Learning disabilities, developmental delays, hyperactivity [chop.edu]

  In children with HH, these include oppositional-defiant disorder (83%), attention-deficit/hyperactivity disorder (75%), conduct disorder (33%) and mood disorder (17%), which are far more common in affected patients compared to their unaffected siblings [rarediseases.org]

The diagnostic approach is basically the same for all masses. Clinical presentation depends upon the location of the tumor.

There is no specific blood work requires for hamartomas. however, if the patient is symptomatic or about to undergo surgical excision, an ECG, urine analysis and blood coagulation parameters must be ordered. An arterial blood gas may be obtained to determine the presence of any lung disorder. All patients about to undergo a lung resection are best served with pulmonary function tests to determine their suitability for surgery. Other blood work depends on location of the hamartoma. If a liver lesion is suspected, the liver function tests should be ordered. All patients are asked to stop smoking for at least 3-4 weeks prior to surgery and pulmonary rehabilitation is undertaken.

Plain Radiography

The first imaging test of choice is always the plan x-ray. However, the plain x-ray is not sensitive for hamartomas and may not even identify small lesions. The plain x-ray may help identify bone fractures or areas of bone thinning. On the plain x-ray, hamartomas usually appear as well circumscribed tumors with smooth margins. Even though calcification is seen in about 15% of lesions, it may not always be visible on x-ray. The radiographic pattern of calcification may resemble popcorn, and although virtually diagnostic, this appearance is not common. Benign lesions tend to have calcium deposited in central, concentric, peripheral, homogeneous or “popcorn” patterns, whereas an irregular pattern of calcification is more likely to be a feature of malignancies. Serial x-rays may show either fast or slow growth, making differentiation from carcinoma difficult. Cavitation is rare seen with hamartomas. In the absence of characteristic popcorn pattern of calcification, x-ray evidence of calcification or evidence of focal areas of fat, the differential diagnosis must include all other solitary nodules, especially cancer.

Bone Scan

Bone scans may be used to differentiate a benign from a malignant lesion. If the patient has evidence of vascular involvement, then angiography is useful.

CT scan
Since the plain x-ray is not sensitive, the CT scan with and without contrast is recommended as it can help define the calcification. In addition, the CT scan can also help make a diagnosis of AV malformation and can reveal the presence of a malignancy. CT scan with use of iodinated contrast dye also provides more details about the size, presence of satellite lesions, status of lymph nodes, and, when used in conjunction with noncontrast studies, more detailed definition of calcification. Specific popcorn like calcifications are almost pathognomonic for a pulmonary hamartoma. The major difficulty with hamartomas is distinguishing them from inflammatory and metastatic lesions.

MRI

MRI has a limited role in evaluation of hamartomas. Focal areas of calcium and fat can be missed because of lack of signal. MRI is useful in defining tumor invasion of the great vessels and chest wall. MRI is superior to CT scan in defining the mediastinum, chest wall invasion and aortopulmonary window adenopathy. MRI is not always available, is expensive and does not really decipher a benign lung tumor from a malignant nodule. MRI though is useful when looking at lesions in the spinal cord and is much more sensitive than CT scan when assessing soft tissue masses.

Bronchoscopy

If a hamartoma is suspected in the airways, Fiberoptic bronchoscopy is very important to evaluate all central lung masses. If the tumor is located centrally, bronchial washing and/or biopsy can be performed. If the mass is a polyploid lesion with a stalk, then the entire mass can be excised at the stalk. Bronchoscopy lacks sensitivity for detecting malignancy for peripheral masses.[8]

Needle Biopsy

Needle biopsy has become a standard approach to making a diagnosis of hamartoma [9] [10].The technique can be combined with either fluoroscopy or CT scan to improve its accuracy. The location of the mass is the most important determining factor for a needle biopsy. Needle biopsy tends to yield more positive results than simple aspiration. The procedure is usually done in a radiology suite. Complications of needle biopsy include bleeding, pain, pneumothorax, infection and failure to make a diagnosis.

Contraindications to biopsy
A needle biopsy or any surgical approach for biopsy of a mass should not be done in the presence of a bleeding diathesis and cardiopulmonary conditions, which may place the patient's life at risk.

Histology

Hamartomas are composed of normal components of the lung tissues. On histologic sections they are composed mainly of hyaline cartilage and glandular tissue that may include fat. The myxoid connective tissue is surrounded by smooth muscle and clefts lined by epithelial cells. However, the mature cells are unorganized and haphazardly arranged. In the lung, histologic studies might show how that the peripheral epithelial line the clefts. Foci of undifferentiated mesenchymal or fibroblast-like cells are frequently present at the periphery of the cartilaginous tissue. Cartilage is always present and is a characteristic feature of hamartomas.

Gross pathology

When a peripheral hamartoma is examined, it is usually a firm mass consisting of lobules of cartilaginous tissue. It is surrounded by a zone of loose fibroblastic tissue. Fatty tissue, smooth muscle cells and monocytes may also be seen in varying proportions. Calcification and ossification is not always present, but when present it can be extensive. This feature accounts for the typical “popcorn calcification” seen on x-rays. In the lung and bone hamartomas are morphologically indistinguishable from malignant lesions but appear more fleshy, polyploid and are often densely adhered to the underlying tissues.

There is no medical therapy for hamartomas apart from observation. The majority of hamartomas are found on an incidental exam. Since most hamartomas cause no symptoms, the treatment is usually conservative. If the hamartoma is compression a nerve or causing pain, analgesics may be administered. If the symptoms persist, then excision may be required.
General indications for surgery include the following:

• Unable to rule out a malignancy
• Presence of a pathological fracture or difficulty with joint function
• Patient has symptoms due to compression or obstruction
• Patient’s function has been compromised

The majority of patients do not require any type of intervention. For those who do require a surgical procedure, this may include a biopsy to rule out a cancer. Other procedures used to remove hamartomas include curettage or fixation of a fracture. In rare cases, a digital amputation may be required.
In patients with a solitary nodule suspected of being a hamartoma in a young nonsmoking patient, one may elect to monitor the individual with serial radiographs as long as the solitary nodule does not double in size in less than a year. The mass should not significantly increase its pattern of calcification and shape consistent with a malignancy, nor should it cause symptoms. Unless an absolute clinical diagnosis of hamartoma can be made, conservative resection is the treatment of choice.
Today hamartomas can be excised using the open technique of using video assisted techniques, depending on where the lesion is located. The lesions can be enucleated without difficulty. It is important to remember that hamartomas are benign lesions and radical surgery is almost never required. Unless the mass is compressing or invading delicate structures, all efforts must be made to remove only the lesion and avoid damage to the normal adjacent tissues.

If one elects to follow the hamartoma clinically, it is recommended that a plain x-ray be obtained regularly. Protocols vary as to the exact timing of x-rays, but one should be obtained every 3-6 months for the first year, then every 12 months in the following year. Some experts recommend that a yearly CT scan should be complementary study if there are any signs of change on the x-ray. This protocol is only recommended in reliable patients who can be followed up. For those who might be lost to follow up or live too far from the medical center, a small surgical procedure will eliminate both the need for follow up and patient/physician anxiety.

Generally, hamartomas do not grow and remain stable in size. However, some hamartomas can grow over time and often tend not to have characteristic calcification. Small hamartomas may not be present in previous x-rays and thus, may not present with symptoms. In such cases, both the patient and the surgeon may be anxious enough to seek a surgical consult. Although hamartomas are benign and do not pose a significant health problem, complications can result if the lesion is compressing a nerve, blood vessel or airway. Overall, these tumors are considered benign, and, therefore, their malignant/cancerous potential is minimal. When there is any doubt, the safest course is to remove it surgically and confirm the diagnosis.

The diagnosis of a hamartoma in almost any part of the body in no way limits normal life expectancy, nor does it predispose the patient to any type of malignancy. The hallmark of surgical treatment of such benign lesions is conservative resection, whenever possible.

Overall, no recurrent tumors have been seen in many series over a period of 20 years. However, there are a few reports of additional hamartomas occurring after resection. The recurrences have frequently been seen after a period of 3-6 years. Other rare reports indicate that perhaps there is an increased risk for subsequent development of pulmonary carcinoma in patients who have hamartomas. Today, these reports are anecdotal. For the present, it is perhaps safer, more cost-effective and less stressful to have the lesion excised and the histology confirmed.

The exact cause of hamartomas is unknown. In some cases, hamartomas have been associated with polyposis and other central neural disorders. Hamartomas have been described in the following organs or medical disorders:

• Bronchus;
• Polyps in Peutz Jegher syndrome;
• Hemangiomas [4];
• In von Recklinghausen diseases multiple neurofibromas are common[5];
• In tuberos sclerosis neuroepithelial cells appear like hamartomas;
• Cowden disease [6][7];
• Hamartomas may also occur in the hypothalamus, colon and bone.

The exact incidence of hamartomas is not known because in most cases these lesions are asymptomatic and never come to medical attention. The majority of hamartomas are only discovered on an incidental exam when the patient is being worked up for another medical disorder. Sometimes the lesions are seen on x-ray and at other times they are discovered during an autopsy. The majority of series on hamartomas indicate that these lesions are most common in children and young adults. Overall, hamartomas are slightly more common in men than women. Most lesions are first identified in the 3rd-4th decade of life. Hamartomas account for nearly 70% of benign coin lesions of the lung.

Hamartomas can occur in almost any organ but are most prevalent on cartilage, bone and fibrous tissues. Although the majority of lesions are less than 2-4 cm in size, some may be as large as 8-10 cm. Hamartomas have been reported in all races.

Hamartomas are thought to be derived from embryonic remnants, representing an abnormal collection of normal tissue components of the organ in which they are found. The tumor consists of disorganized collection of smooth muscle cells, cartilage and collagen. These tumors are believed to arise in the connective tissues, bone or cartilage. They tend to be well circumscribed, lobulated and the contiguous tissues may be condensed. Sometimes the tumor may be calcified and appear like a “popcorn” lesion.

Rarely there maybe multiple hamartomas which may occur in either the same organ or at a different anatomical site. Reports of recurrences after excision have also been reported. Hamartomas chiefly occur in bone, cartilage, and soft or fibrous tissues.

The cause of hamartoma is not known and hence prevention strategies do not exist. Patients who have a systemic disorder like neurofibromatosis, cowden disease or peutz jegher syndrome need  follow up with their healthcare provider to ensure that the lesions are not causing any symptoms.

The term hamartoma was first coined by Albrecht, who in 1904 described a disorganized arrangement of normal tissues present in an organ. A hamartoma is a mass composed of tissues that are normally present in the organ in which the tumor occurs, but the tissue elements are disorganized. Histologically, hamartomas consists of cleft epithelial tissue and other tissues such as fat and cartilage. When a hamartoma is believed to exist in the tissues, the most important diagnostic consideration is to rule out a malignancy. Except for a biopsy, there is no absolute method of confirming the presence of a hamartoma. Hamartomas can be easily enucleated during surgery. Unless the lesion has invaded local tissues, major resection is rarely required [1-3].

Hamartoma is a benign lesion that may occur in any part of the body including bone, soft tissue and cartilage. In most cases, these lesions do not cause any symptoms and are discovered as an incidental finding. In rare cases, a hamartoma will cause pain, swelling, bleeding or a cough. The diagnosis of a hamartoma is made with a needle biopsy. The decision to treat a hamartoma depends on patient preference. These lesions are harmless and can be observed. They do not become cancerous. However, if you feel anxious or are worried, then surgery to remove the lesion is usually curative.

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