Considerations in the Assessment of Myelofibrosis

Ruben A. Mesa, MD, FACP:This 72-year-old gentleman presented with myelofibrosis in a way that many patients do. He went to his primary doctor because he wasn’t feeling well. He’d had abdominal symptoms. He had fatigue, night sweats, and unexpected weight loss. His primary physician examines him, finds a spleen that is markedly enlarged, blood studies are done, and the patient is found to have anemia, unexpected leukocytosis, and some circulating blasts. A subsequent bone marrow confirms that he hasJAK2V617F-mutated myelofibrosis with a chromosomal abnormality in chromosome 20, which is fairly common. So this is a classic presentation of primary myelofibrosis.

Myelofibrosis can present in a variety of ways. First, in individuals for whom it is the initial diagnosis, as primary myelofibrosis, we were unaware they had a hematologic malignancy. This case very much fits that picture. There were several months, sometimes a year, sometimes a year and a half of worsening difficulties. Those difficulties come from a variety of areas. One, they may be symptoms related to the spleen. That could be abdominal discomfort, it could be fullness, or it could be that their pants aren’t fitting right or look unusual in some way. It could be the presentation of symptoms: Unexpected weight loss, sometimes early satiety. “I’m filling up early when I eat.” It could be a pronounced fatigue or night sweats.

Additionally, patients can present as having evolved into myelofibrosis from previously having had ET [essential thrombocythemia] or polycythemia vera [PV]. Now, that presentation is a little different. Those individuals would have been managed sometimes for a handful of years to many years, frequently 10 years or more, and would have had diminishment in their blood counts. They would have noted those same sort of symptoms or features, in terms of their spleen potentially enlarging. They would have noted, potentially, a change in their symptoms. So it’s not uncommon that the patient who comes to me who now has post-PV myelofibrosis is a patient who tells me that 6 months ago, or 1 year ago they really noticed a change with worsening fatigue, unexpected weight loss, and potentially, abdominal symptoms.

When evaluating the patient for myelofibrosis, an accurate sense of the spleen is important. Most commonly, that’s by physical examination with the standard measuring of the number of centimeters below the left costal margin in the midclavicular line.

That location is probably only important just to be consistent in the area in which it is measured. Indeed, measuring it by palpation, given the irregular size of the spleen, can be fraught with some challenges.

One, it’s important to measure in the same spot. Two, it’s important to have a consistent approach to where it is in the patient’s breathing cycle. Taking a deep inhalation or expiration certainly will move the spleen. It doesn’t matter which approach you take, but it does matter that you are consistent.

It is for these reasons that the clinical trials with myelofibrosis have frequently used a volumetric assessment by MRI [magnetic resonance imaging], or CT [computed tomography], or ultrasound, because evaluation of the spleen by palpation is certainly as much an art as it is a science.

Misdiagnosis of myelofibrosis certainly can occur, with the common confounders being first among the other myeloid disorders. Fibrosis can be present in chronic myeloid leukemia [CML], or it can be present in MDS/MPN [myelodysplastic/myeloproliferative neoplasms] overlapped syndromes, or in myelodysplastic syndrome with fibrosis. All of these are chronic myeloid malignancies, but the differences between them are important and may have relevance in terms of treatment. In particular, if they haveBCR-ABLand are CML with fibrosis.

Additionally, it’s important to know that although not common, secondary causes of fibrosis continue to remain, including autoimmune diseases, chronic infectious processes, and others. Now with the advent of the MPN-associated driver mutations, theJAK2V617F, the calreticulin mutation, theMPL, these certainly help to provide great clarity. I strongly advise all of my colleagues to use the WHO [World Health Organization] diagnostic criteria to be certain they have the right diagnosis for the patient. The current NCCN [National Comprehensive Cancer Network] guidelines also request that the WHO criteria be utilized in diagnosing these patients.

Transcript edited for clarity.

Case: 72-Year-Old Man Diagnosed With Primary Myelofibrosis

December 2018

• A 72-year old man presents to primary care physician with complaints of fatigue, headache, night sweats, poor appetite, and 10-15lb weight loss over past few months; report of increased abdominal pain over the last 3 months
• PMH: mild hypertension
• PE: BP 130/85; Splenomegaly ~14 cm below left costal margin
• Lab values:
  • HGB: 8.9 g/dL
  • Platelets: 189 x 10⁹/L
  • WBC: 27.2 x 10⁹/L
  • Serum LDH: 1500 U/L
  • Serum EPO: 11.5 mU/mL
• Bone Marrow Biopsy:
  • MF-2
  • Circulating blasts, 1.2%
  • JAK-V617F mutation, del(20q)
• Diagnosis: Primary myelofibrosis