A hamartoma is mostly a benign mass of disorganized tissue native to a particular anatomical location. Most hamartomas are usually benign, but malignant transformation may occur. Hamartomas can grow almost anywhere on the body and typically are found in the lungs, hypothalamus, breast, colon, etc.

Most cases are asymptomatic and discovered incidentally while evaluating other medical conditions. Hamartomas cause morbidity by various mechanisms such as; infection, infarction, pressure/obstruction, hemorrhage/anemia, fracture, and neoplastic transformation. 

Hamartomas result from abnormal normal tissue formation and sometimes occur sporadically and a few times as a part of a syndrome. Hamartoma is most likely due to a developmental error and may appear in several sites. It grows at the same rate as the original tissue. Some genes are also involved in the pathogenesis of hamartoma development, including SMAD4, PTEN, STK1, and BMPR1A.

There are many hereditary syndromes associated with hamartomatous formation, including:

• Tuberous sclerosis

• Cowden syndrome

• PTEN hamartoma tumour syndrome                   

• Peutz-Jeghers syndrome, etc.

Epidemiology

Generally, males are affected more commonly than females by hamartomas. There is no particular evidence of racial predilection. The incidence of most hamartomas remains unknown except for pulmonary hamartoma, in which the incidence rate is approximately 0.25%. Pulmonary hamartomas are 8% of all lung tumors; most of them are diagnosed incidentally. The most common patient age range is 40 to 70. Benign breast lesions have demonstrated correlations with age, hormonal factors, obesity, and family history. Increased age and BMI also increase the risk of colonic polyps.

Hamartomas are fundamentally comprised of disordered replications of normal tissue cells. The underlying mechanisms of anomalous replications are not fully recognized. The particular property is a clearly demarcated mass mainly containing fat and cartilage, but other tissue cells may also be present depending on the anatomic location. The size of most hamartomas is between 1 to 3 cm. Hamartomas are usually not encapsulated and have multiple lobes divided by septations.

A broad spectrum of disorders and syndromes is associated with gene mutations, resulting in multiple hamartomas in various body parts—loss of function of the PTEN gene by mutation results in PTEN hamartoma tumor syndrome (PHTS). Cowden syndrome is the best-studied phenotype within PHTS.In addition to multiple hamartoma formation, patients have dermatologic manifestations such as oral fibromas, trichilemmomas, and punctate palmoplantar keratoses. These are also associated with increased malignant potential.

Histopathology

On microscopic examination, hamartomas have characteristics similar to any benign tumor, such as haphazard growth of the normal tissue and architectural pattern of cytologically normal cells native to the local site. There is usually no sign of metastasis or local invasion.

Usually, adipocytes and single chondrocytes appear in lacunae with an abundant neighboring matrix, and some other cell types may also be found depending on the site of origin.

History and Physical

History taking is a significant aspect of forming a diagnosis of hamartoma and related syndromes. It is crucial to understand the cause and associated conditions. Although hamartomas are usually asymptomatic, complete family and case history can help determine the prognosis. Patient history specific to the related condition is also necessary. Common symptoms and physical findings related to the site of origin are as follows:

Hypothalamus: seizure, altered mental status, vision changes, early-onset pubarche, behavioral changes.

Lung: chronic cough, hemoptysis, fever,  respiratory sounds, e.g., coarse crackles on inspiration, obstructive symptoms

Heart: chest pain, palpitations, edema, dyspnea, cyanosis, cool and clammy skin, murmur, arrhythmia

PTEN/Cowden Syndrome: These syndromes involve multiple tissues, i.e., breast, thyroid, gastrointestinal, genitourinary, and mucocutaneous, and clinical manifestations depend on the extent of involvement of these

Other less common symptoms and physical findings involving the kidney, spleen, and other organs include flank pain, abdominal pain, recurrent infections, fever, night sweats, palpable abdominal mass, increased testicular size, and increased breast size.

Evaluation

Laboratory Testing

• Complete blood count

• Serum electrolytes

• Calcium

• Phosphate

• Potassium

• Urea

• Liver function tests

• CD8

Chest X-Ray 

On chest radiography, lung hamartomas characteristically demonstrate sharply demarcated pulmonary nodules and popcorn calcification. There are no CXR findings associated with other types of hamartomas.

CT Scan                

On a CT scan, a hamartoma demonstrates localized collections of fat alternating with foci of calcification. It is the diagnostic imaging test of choice.

MRI 

On MRI, hamartoma is specified by a heterogeneous signal in T1 and a high signal because of fat and cartilaginous components in T2. It is the diagnostic imaging test of choice for the hypothalamus and most abdominal visceral hamartomas, i.e., kidney, spleen, and pancreas.

Ultrasound

Ultrasound can prove beneficial in the diagnosis of splenic hamartomas.

Bronchoscopy 

Bronchoscopy is useful in the diagnosis of endobronchial hamartomas.

Most cases of hamartoma are asymptomatic and found incidentally. Other patients are treated conservatively with supportive management, such as analgesics used for the pain. If the patient is unresponsive, further investigations are required. Surgical treatment is a consideration in unresponsive patients and is the treatment modality of choice for hamartomas. Surgery is also indicated for diagnostic confirmation, mass symptoms, and cosmetic reasons.

• Lung: A pulmonary nodule is generally an incidental finding. Subsequent management depends on specific features and the probability of malignancy. The nodule is usually a small, well-defined lesion less than 30mm. Lesions larger than 30mm are associated with increased chances of malignancy. Non-surgical techniques such as bronchoscopic-guided transbronchial biopsy (TBB) can be performed for lesions with an intermediate risk of malignancy or in patients who are not surgical candidates. The gold standard for diagnosing a pulmonary nodule is a surgical excisional biopsy, which is curative for some malignancies.Imaging(CT/PET Scans) can be used to identify the best location for biopsy or staging.

• GIT: Hamartomatous polyps are primarily asymptomatic and do not require any specific treatment, but the polyps may grow progressively and becomes symptomatic or even undergo a malignant transformation in patients of Peutz-Jeghers syndrome. These polyps should undergo surgical resection. In some complicated cases, nutritional support, steroids, immunosuppressants, acid suppression, and antibiotics are used in the treatment.

• Breast: Breast hamartomas are usually asymptomatic and found incidentally on screening mammography or may present as painless encapsulated masses. These lesions are usually benign, and only observation is required as management. Symptomatic or suspicious hamartomas should be surgically excised.

• Cowden Syndrome: As it involves various organs and complications, a multi-disciplinary approach is required. Benign and asymptomatic lesions are treated conservatively, while the symptomatic and suspicious lesions are surgically resected. In addition, cancer surveillance and genetic testing are also required in these patients.

Differential Diagnosis

The following are some conditions that have overlapping presentations with hamartoma and require evaluation.

• Hypothalamic-chiasmatic glioma

• Craniopharyngioma: It is a suprasellar tumor that arises from a remnant of Rathke's pouch. It has bimodal distribution: one mode from 5 to 14 years; and a second peak at 50 to 75 years. Due to the mass effect, it can cause compression of the optic pathway leading to  visual symptoms 

• Rathke's Cleft Cyst: Usually asymptomatic but can manifest with headache, visual disturbances, and hypopituitarism.

• Pituitary macroadenoma: Mass symptoms and increased hormonal side effects, such as nausea, headache, vomiting, gigantism, and visual disturbances

• Meylolipoma: Usually presenting as an asymptomatic pulmonary nodule. 

• Pulmonary Chondroma: Pulmonary chondromas are usually associated with Carney's triad. On CT scan, chondromas appear as smoothly marginated, round, or slightly lobulated, small fat-containing areas. Pulmonary chondromas are common in adolescents or young adults.

• Lipoma

• Metastasis

• Rhabdomyoma

• Fibroma

• Paraganglioma

• Splenic hemangioma

• Retroperitoneal liposarcoma

• Adrenal myelolipoma

Surgical Oncology

Following are some different treatment modalities for differing anatomical sites

Pulmonary Hamartoma

• Wedge resection is the treatment of choice for patients with pulmonary hamartoma.

• Aggressive lobectomy or total pneumectomy is also an option in some cases.

• An intraoperative frozen section is mandatory to rule out malignancy.

Hypothalamic Hamartoma

• MRI-guided stereotactic laser ablation is one of the most effective approaches.

• Others include;  transsphenoidal microsurgery, gamma knife radiosurgery, and thermocoagulation.

• A few other surgical approaches are also options, with varying outcomes.

Breast Hamartoma 

• For definitive diagnosis and treatment, surgical excision is usually done.

• Although, in most cases, the malignant potential of breast hamartoma is usually the same as normal breast tissue, partial or complete mastectomy is considered in large masses and sometimes for cosmetic and psychological indications.

Radiation Oncology

High-dose radiations on a focused location, such as the hypothalamus hamartomatous lesion, can be effective. Gamma knife radiosurgery uses highly focused gamma rays, and therefore it is a distinctly precise procedure.

Although it uses highly focused radiation beams and is relatively safer than traditional radiation therapy, it can also cause various adverse effects such as nausea, vomiting, fatigue, skin blistering, dysphagia, brain edema, and headache. Long-term treatment with radiation also increases the risk.

Enhancing Healthcare Team Outcomes

Although hamartomas are usually benign, they should be monitored continuously for malignant potential. The interprofessional healthcare team is generally necessary due to the complex and diverse presentation of patients. This interprofessional team includes primary care clinicians (MDs, DOs, NPs, and PAs) who might first discover the hamartoma incidentally during an examination for other problems or as a chief complaint, an oncologist to verify the diagnosis and determine the prognosis, and the nursing staff who can assist in patient evaluation, counsel the patient, and serve as liaisons between the various healthcare disciplines involved in the case. All interprofessional team members must maintain meticulous records of each interaction or intervention with the patient.

A screening program should be in place for earlier detection to achieve better outcomes. Good communication, along with detailed and smooth information sharing, are essential components for better outcomes. Interprofessional care must involve an evidence-based approach to planning and evaluating these cases.

Prognosis

Hamartomas are usually benign, but malignant transformation may occur in some cases, e.g., in Cowden syndrome, where there is an increased risk of breast, thyroid, and endometrial cancer. The prognosis of hamartoma usually depends on the location and size of the mass and the comorbid conditions. Large-sized masses in the kidneys, hypothalamus, or spleen pose more significant health issues.

Complications

Hamartomas are usually asymptomatic and rarely lead to complications. But some lesions can grow to enormous sizes and cause internal disfigurement and pressure on surrounding organs, which can even lead to life-threatening symptoms. It can lead to seizures, heart failure, breathing difficulty, breast deformity, abdominal pain, etc., depending upon the location of these lesions.

A rare inherited disorder marked by the presence of many benign (not cancer) growths called hamartomas and an increased risk of cancer. Hamartomas form in different parts of the body, especially the skin, mouth, and gastrointestinal tract. Other benign tumors may also occur in the thyroid, breast, uterus, soft tissue, and brain. Other signs and symptoms include a larger-than-average head, abnormal skin changes, blood vessel problems, autism spectrum disorder, and learning and developmental delays. People with multiple hamartoma syndrome have an increased risk of developing certain types of cancer, including melanoma and cancers of the breast, thyroid, endometrium, kidney, colon, and rectum. Multiple hamartoma syndrome is usually caused by mutations (changes) in the PTEN gene. Also called Cowden disease and Cowden syndrome.

Tumors are abnormal growths in your body. They can be either benign or malignant. Benign tumors aren't cancer. Malignant ones are. Benign tumors grow only in one place. They cannot spread or invade other parts of your body. Even so, they can be dangerous if they press on vital organs, such as your brain.

Tumors are made up of extra cells. Normally, cells grow and divide to form new cells as your body needs them. When cells grow old, they die, and new cells take their place. Sometimes, this process goes wrong. New cells form when your body does not need them, and old cells do not die when they should. These extra cells can divide without stopping and may form tumor.

Treatment often involves surgery. Benign tumors usually don't grow back.

Uterine fibroids are the most common benign tumors in women of childbearing age. Fibroids are made of muscle cells and other tissues that grow in and around the wall of the uterus, or womb. The cause of fibroids is unknown. Risk factors include being African American or being overweight.

Many women with fibroids have no symptoms. If you do have symptoms, they may include

• Heavy or painful periods or bleeding between periods
• Feeling "full" in the lower abdomen
• Urinating often
• Pain during sex
• Lower back pain
• Reproductive problems, such as infertility, multiple miscarriages or early labor

Your health care provider may find fibroids during a gynecological exam or by using imaging tests. Treatment includes drugs that can slow or stop their growth, or surgery. If you have no symptoms, you may not even need treatment. Many women with fibroids can get pregnant naturally. For those who cannot, infertility treatments may help.

Tuberous sclerosis is a rare genetic disease that causes benign tumors to grow in the brain and other organs. Symptoms vary, depending on where the tumors grow. They could include

• Skin problems, such as light patches and thickened skin
• Seizures
• Behavior problems
• Intellectual disabilities
• Kidney problems

Some people have signs of tuberous sclerosis at birth. In others it can take time for the symptoms to develop. The disease can be mild, or it can cause severe disabilities. In rare cases, tumors in vital organs or other symptoms can be life-threatening.

Tuberous sclerosis has no cure, but treatments can help symptoms. Options include medicines, educational and occupational therapy, surgery, or surgery to treat specific complications.

Neurofibromatosis is a genetic disorder of the nervous system. It mainly affects how nerve cells form and grow. It causes tumors to grow on nerves. You can get neurofibromatosis from your parents, or it can happen because of a mutation (change) in your genes. Once you have it, you can pass it along to your children. Usually the tumors are benign, but sometimes they can become cancerous.

There are three types of neurofibromatosis:

• Type 1 (NF1) causes skin changes and deformed bones. It usually starts in childhood. Sometimes the symptoms are present at birth.
• Type 2 (NF2) causes hearing loss, ringing in the ears, and poor balance. Symptoms often start in the teen years.
• Schwannomatosis causes intense pain. It is the rarest type.

Doctors diagnose the different types based on the symptoms. Genetic testing is also used to diagnose NF1 and NF2. There is no cure. Treatment can help control symptoms. Depending on the type of disease and how serious it is, treatment may include surgery to remove tumors, radiation therapy, and medicines.

A polyp is an extra piece of tissue that grows inside your body. Colonic polyps grow in the large intestine, or colon. Most polyps are not dangerous. However, some polyps may turn into cancer or already be cancer. To be safe, doctors remove polyps and test them. Polyps can be removed when a doctor examines the inside of the large intestine during a colonoscopy.

Anyone can get polyps, but certain people are more likely than others. You may have a greater chance of getting polyps if you

• Are over age 50
• Have had polyps before
• Have a family member with polyps
• Have a family history of colon cancer

Most colon polyps do not cause symptoms. If you have symptoms, they may include blood on your underwear or on toilet paper after a bowel movement, blood in your stool, or constipation or diarrhea lasting more than a week.

An acoustic neuroma is a benign tumor that develops on the nerve that connects the ear to the brain. The tumor usually grows slowly. As it grows, it presses against the hearing and balance nerves. At first, you may have no symptoms or mild symptoms. They can include

• Loss of hearing on one side
• Ringing in ears
• Dizziness and balance problems

The tumor can also eventually cause numbness or paralysis of the face. If it grows large enough, it can press against the brain, becoming life-threatening.

Acoustic neuroma can be difficult to diagnose, because the symptoms are similar to those of middle ear problems. Ear exams, hearing tests, and scans can show if you have it.

If the tumor stays small, you may only need to have it checked regularly. If you do need treatment, surgery and radiation are options.

If the tumors affect both hearing nerves, it is often because of a genetic disorder called neurofibromatosis.