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Continuing Education Activity

A hamartoma is a local malformation made up of an abnormal mixture of cells and tissue. Although most hamartomas are benign, they cause morbidity by various mechanisms such as; infection, infarction, pressure/obstruction, hemorrhage/anemia, fracture, and neoplastic transformation. 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. Avoiding the high morbidity and mortality associated with this condition requires prompt diagnosis and treatment. This activity reviews the evaluation and treatment of hamartoma and highlights the role of the interprofessional team in evaluating and treating patients with this condition.


  • Describe the pathophysiology of hamartoma.
  • Summarize the epidemiology of hamartoma.
  • Outline the typical imaging findings associated with pulmonary hamartoma.
  • Review the importance of improving care coordination amongst interprofessional team members to improve outcomes for patients affected by pituitary hamartoma.


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.[1]

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[2]
  • PTEN hamartoma tumour syndrome                   
  • Peutz-Jeghers syndrome, etc.[3][4]


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.[5][6]


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.[7][8]

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.[9]


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.[10]

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.[11]

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[9]

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.


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.[12]

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.


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 can prove beneficial in the diagnosis of splenic hamartomas.[13]


Bronchoscopy is useful in the diagnosis of endobronchial hamartomas.

Treatment / Management

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.[14]

  • 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.[15][16]
  • 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.[17]
  • 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.[18]
  • 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.[19]

Hypothalamic Hamartoma

  • MRI-guided stereotactic laser ablation is one of the most effective approaches.
  • Others include;  transsphenoidal microsurgery, gamma knife radiosurgery, and thermocoagulation.[20]
  • A few other surgical approaches are also options, with varying outcomes.[21]

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.[22]

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.


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.[23]


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.

Deterrence and Patient Education

Various non-profit organizations are devoted to education, information provision, and support to hamartoma patients and healthcare providers while promoting research towards early detection, better treatments, quality of life, and cure. General health campaigns, discussions, and public awareness programs on different platforms can play a huge role in further deterrence.[24]

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.[25]



Syed Awab Ali


Francesk Mulita


3/14/2023 6:05:01 PM



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