Chloroma: Definition, Causes, Symptoms, Diagnosis, Treatment and Prognosis

We are talking about a green malignant tumor of myeloid cells.

Chloroma is a solid tumor composed of an extramedullary proliferation similar to a mass of primitive cells of the myeloid lineage that causes the removal of the native tissue architecture.

The first case of chloroma was observed by the British physician Burns in 1811 in his observations on the surgical anatomy of the head and neck.

Later, in 1853, King coined the term “chlorome,” since the tumor was often greenish in color due to the presence of the enzyme myeloperoxidase.

However, it was observed that up to a third of these tumors can be white or gray. Therefore, Rappaport proposed the term granulocytic which is preferred and used interchangeably with chlorome.

Causes

Chloroma can develop at any age. However, almost 60% of cases are seen in children under 15 years of age with no specific gender predilection. It is a rare manifestation of acute myeloid leukemia (AML) with a reported incidence of 2.5–9%.

It can occasionally be seen in other myeloproliferative or myelodysplastic conditions, such as myeloid metaplasia, polycythemia vera, hypereosinophilic syndrome, or essential thrombocytosis. Rare case reports also suggest its occurrence in lymphoid leukemia.

The chronology of the appearance of chloroma in myeloproliferative or myelodysplastic disorder is variable; consequently, the following patterns can be seen:

  • Concurrent with AML : Most common, manifesting at the time of initial presentation or at any time during the active phase of AML.
  • Relapse : occurs months or years later in remission of AML, especially in bone marrow transplant recipients. Chloroma that develops during remission is considered a systemic disease despite normal blood counts and bone marrow findings.
  • Precursor to blast phase transformation : in non-leukemic myeloproliferative conditions, heralding the blast crisis and subsequent AML transformation.
  • Primary Chloroma : A rare, non-leukemic form that occurs in an otherwise healthy population in the absence of a marrow abnormality. Primary chloroma precedes any hematologic abnormality in nearly 35% of cases. It generally undergoes a leukemic transformation in months or years, with an average interval of 10 months.

Certain risk factors that increase the likelihood of developing chloroma in AML include M4 or M5, specific T-cell markers expressing CD13 and CD14 myeloblasts, high total peripheral leukocyte counts, and certain to inv chromosomal abnormalities.

In contrast, chloroma in AML relapse may be due to certain biological peculiarities of leukemic blast cells, such as the molecular expression of markers responsible for increased tissue infiltration (CD87) and adhesion (CD56 and CD138).

The frequent predilection of these lesions at certain sites supports the hypothesis of a suboptimal response to chemotherapy or graft versus leukemia response.

The most common sites of chloroma are the bone and the periosteum, explained by direct spread from the adjacent infiltrated medulla.

Other frequently involved sites are the skin (leukemia cutis), lymph nodes, and orbit, although any site can potentially be affected. Chloroma has a high propensity for recurrence with a variable spatial and temporal distribution.

Chloroma symptoms

In many cases, granulocytic sarcomas do not cause significant symptoms, and approximately 50% of chloroma cases are diagnosed only at autopsy.

Chloroma symptoms are usually caused by the mass itself or by the way it affects the organ in which it is located. Chloroma in the CNS is associated with symptoms such as cauda equina syndrome or radiculopathy.

Diagnostic modalities

Chloroma generally remains asymptomatic (approximately 50%) or may have nonspecific manifestations related to mass effect, organ dysfunction, or pain at the affected site.

The cross-sectional image is essential to delineate the sites and degree of involvement in addition to characterizing these lesions.

The role of plain radiography is restricted to the evaluation of skeletal manifestations and the preliminary evaluation of pulmonary lesions or intestinal obstruction.

Ultrasound is useful for evaluating superficial structures such as the skin, testicles, or during follow-up for abdominal injuries.

Chloroma is a soft tissue tumor that can be circumscribed or diffusely infiltrated. CT findings are variable, depending to some extent on the site of involvement.

Craniospinal lesions are generally hyperdense on nonenhanced CT (NCCT) and show intense homogeneous enhancement on contrast-enhanced CT (CECT). In contrast, lesions in the abdominal viscera and orbits are frequently hypodense and slightly improve.

MRI is useful for the evaluation of craniospinal and musculoskeletal involvement, especially in indeterminate cases. On MRI, it is iso / hypointense on T 1 and slightly hyperintense on T 2. MRI is also suitable for imaging due to the lack of radiation problems.

Nuclear imaging such as fluorine-18 fluxiglucose (18F-FDG), positron emission tomography (PET) / CT scan, and gallium-67 are valuable for assessing multiplicity and evaluating response after chemotherapy.

On 18 F-FDG-PET / CT and gallium-67 scans, chloroma shows avid uptake. 18 F-FDG-PET is essential in radiation therapy planning.

Despite all of these imaging modalities, findings on ultrasound, CT, MRI, or 18 F-FDG-PET remain generic, indistinguishable from other malignancies, and are often mistaken for lymphoma, a much more common hematologic neoplasm.

Diagnostic confirmation of chloroma is essentially established by immunohistochemistry (IHC) by demonstrating monoclonal antibodies against certain specific surface antigens. The most expressed markers are CD43, CD 68 and lysozyme.

According to the classification of the World Health Organization (2008), the specific cytochemical stains for the diagnosis of chloroma must include chloroacetate esterase, myeloperoxidase and non-specific esterase.

A horde of other markers that can be expressed include CD4, CD33, CD34, CD56, CD117, or terminal deoxynucleotidyl transferase depending on the lineage and maturation of the myeloid cells.

There is a high probability of misdiagnosis in the pathology, in as high as 47% of cases due to the lack of specific application of IHC markers, if preventive chlorome chlorination is suspected in the image, especially in the non-leukemic form.

Treatment and prognosis

Due to its rarity, there is limited data availability to establish the exact incidence of chloroma in the prognosis of leukemia or other myeloproliferative conditions.

In AML, the prognosis remains largely unchanged; however, studies suggest refractoriness to therapy and a greater likelihood of relapse.

In contrast, primary myeloid sarcoma or chloroma in remission of AML are classified as systemic diseases and are treated in leukemia lines even with normal peripheral leukocyte or bone marrow (BM) counts.

Similarly, chloroma in several other myeloproliferative and myelodysplastic conditions suggests leukemic transformation and warrants systemic anti-leukemic chemotherapy.

Localized treatment, such as surgery or radiation therapy, is very effective in relieving compression symptoms, especially in spinal chloroma, and can provide immediate survival benefits in some cases; however, overall survival or prognosis are not affected and are determined by systemic disease.

On average, the median survival after a chloroma diagnosis is 7.5 months. Prognosis is not affected by age, gender, or the underlying myeloproliferative / myelodysplastic condition.

In general, the forecast is independent of the participation site; however, injuries at rare sites can be detrimental primarily due to delayed recognition, although injuries may not necessarily be more aggressive than their counterparts elsewhere.

A recent increase in the incidence of chloroma is likely due to the prolonged longevity of the leukemia as a consequence of the availability of new treatment options (eg, allogeneic bone marrow transplantation, repeat donor lymphocyte infusion, second transplant) .

However, the diagnosis of chloroma, especially the non-leukemic form, is quite challenging and is essentially a holistic approach involving clinical, laboratory, and imaging findings.

Radiologists are often the standard bearers in reaching the diagnosis by raising their suspicion on the images that guide the hematopathologist to run flow cytometry, IHC, and immunophenotyping accordingly.

For impact on prognosis and overall survival, radiologists must be aware of possible imaging manifestations, potential sites of involvement, particularly in known hematologic malignancies, to alarm their suspicion.

In this way, early diagnosis is facilitated, which can alter management and stop the progression of the disease. Few series also reported a lower rate of leukemic transformation if primary MS is recognized and treated early.

Despite aggressive and extensive involvement, these lesions are highly sensitive to induction chemotherapy; in addition, highlighting the need for timely recognition.

Summary

Chloroma refers to the extramedullary proliferation of immature myeloid precursors that occur in a range of myeloproliferative and myelodysplastic conditions; Acute myeloid leukemia is the most common.

With nonspecific imaging and clinical manifestations, you are at high risk of misdiagnosis that can significantly affect the outcome of an otherwise treatable injury. Also with these injuries announcing impending explosion crises, awareness of the imaging findings becomes imperative.

Imaging not only helps raise suspicion, but also guides further confirmation by demonstrating specific immunohistochemical markers, ensuring the timely institution of chemotherapy.

In general, the solid lesions that improve in any hematologic disorder could be chloromas, especially if they are multifocal with mass effect.