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

Hypothalamus: seizure, altered mental status, vision changes, early-onset pubarche, behavioral changes.[9]

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

Other less common symptoms and physical findings involving 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.[10]

CT Scan                

On 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 high signal because of fat and cartilaginous components in T2. It is the diagnostic imaging test of choice of the hypothalamus and most of the abdominal visceral hamartomas, i.e., kidney, spleen, pancreas.

Ultrasound

Ultrasound can prove beneficial in the diagnosis of splenic hamartomas.[11]

Bronchoscopy 

Bronchoscopy is useful in the diagnosis of endobronchial hamartomas.

Most of the cases of hamartoma are asymptomatic and found incidentally. Other patients are treated conservatively with supportive management. Surgical treatment is a consideration in unresponsive patients, and it is the treatment modality of choice for hamartomas. Surgery is also indicated for diagnostic confirmation, mass symptoms, and for cosmetic reasons.[12]

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: 5 to 14 years; and a second peak at 50 to 75 years. Due to 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

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.[13]

Hypothalamic Hamartoma

• MRI-guided stereotactic laser ablation is one of the most effective approaches.
• Others include;  transsphenoidal microsurgery, gamma knife radiosurgery, thermocoagulation.[14]
• There are a few other surgical approaches that are also options, with varying outcomes.[15]

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.

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.[16]

Although it uses highly focused radiation beams and 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. Longterm 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.[17]

Hamartomas can grow to enormous sizes and cause disfigurement and pressure on surrounding organs internally, which can lead to life-threatening symptoms. It can lead to seizures, heart failure, breathing difficulty, breast deformity, and abdominal pain, etc.

There are various non-profit organizations 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.[18]

Although hamartomas are usually benign, they should be monitored continuously for malignant potential. The interprofessional team is generally necessary due to the complex and diverse presentation of patients. For a better outcome, a screening program should be in place for the earlier detection. Good communication, along with detailed and smooth information sharing, are essential components for better outcomes. The interprofessional care must involve an evidence-based approach to planning and evaluation of the cases.[19]