Submitting Author: Stonecypher, Mark Saddler, MD,PhD
Institution: Hosp Univ of Pennsylvania
Additional authors:Joseph Hatem MD, Craig Soderquist MD, Adam Bagg, MD
Session: Extramedullary manifestations of myeloid neoplasms

A 56-year-old male presented to an outside hospital in July 2012 complaining of 4 months of back pain. Imaging demonstrated a paraspinal mass at T7. A needle biopsy showed necrosis and although non-diagnostic was presumed to be of neoplastic origin. Clinically, the differential diagnosis included malignant peripheral nerve sheath tumor, chordoma, and metastatic carcinoma, amongst others. The patient subsequently underwent a T5-T9 decompressive laminectomy with fusion and resection of the mass at the Hospital of the University of Pennsylvania on August 10, 2012. A CBC showed WBC 6.1, HGB 10.4, MCV 90, and PLTs 189.

The submitted specimen was fixed in formalin and H&E sections revealed sheets of markedly atypical intermediate sized cells with round to irregular nuclei, fine chromatin, occasionally prominent nucleoli, and moderate amounts of granular eosinophilic cytoplasm; occasional apoptotic cells and mitotic figures were identified. The histologic differential diagnosis (emanating from neuropathology) was broad and included soft tissue sarcomas, numerous poorly differentiated tumors, and hematolymphoid malignancies.

By immunohistochemistry, the neoplastic cells were positive for CD43, CD45, CD68, CD117 and MPO, but negative for all other evaluated antigens.

Given the diagnosis of a granulocytic sarcoma (extramedullary acute myeloid leukemia), a bone marrow was performed (see tandem PowerPoint presentation). The Wright-Giemsa stained aspirate showed focal collections of blasts (60% overall) with round and occasionally bilobed and reniform nuclei, variably condensed chromatin, occasionally prominent nucleoli, and moderate amounts of granular cytoplasm; no Auer rods were identified. An H&E stained section of the B5-fixed core biopsy was remarkable for patchy involvement, with foci of blasts and intervening normal marrow.

Flow cytometry on the bone marrow aspirate demonstrated a discrete expanded population of blasts (27%) with the following dominant immunophenotype: CD13+ CD33+ CD64+ CD117+ MPO+ HLA-DR- with dim variable expression of CD2, CD4, and CD34.

Bone marrow: 46,XY,t(15;17)(q24;q21)[15]/46,XY[5]. FISH confirmed a PML-RARA fusion.

Bone marrow: Multiplex reverse transcription-polymerase chain reaction analysis was positive for a PML-RARA fusion mRNA transcript (short form). A FLT3 ITD was also identified. No NPM1 mutation was detected.

This case represents a most unusual extramedullary presentation of an acute promyelocytic leukemia (APL).

The paraspinal mass was initially evaluated by neuropathology, with a broad histologically-based differential diagnosis. Once CD45 was shown to be positive (and cytokeratin AE 1/3 negative), a lymphoma was favored; however, the neoplasm did not express B- or T-cell antigens. This led to a consideration of a possible myeloid origin.

Extramedullary acute myeloid leukemia (AML) is seen in less than 10% of cases of AML, and occurs more frequently in those with (myelo)monocytic morphology and in AML with t(8;21)(q22;q22). The exact frequency of APL presenting this way is unknown; however, at least 5 cases have been reported in the literature. Interestingly, the patient had a 4-month history of back pain prior to seeking medical attention, the bone marrow showed only patchy involvement, and the CBC was relatively well maintained indicating the rather slow evolution of this typically aggressive acute leukemia. While the use of ATRA has been associated with unusual extramedullary relapse of APL, presentation in this manner is most unusual. Furthermore, since APL is a molecularly defined entity with a specific treatment and favorable prognosis, this case highlights the need for accurate subclassification of granulocytic sarcomas for optimal patient care.

Acute promyelocytic leukemia, t(15;17)(q24;q21)/PML-RARA positive, with a most unusual presentation as an apparently slow growing paraspinal mass.

Acute promyelocytic leukemia with t(15;17)(q24.1;q21.2), PML-RARA, and FLT3 ITD mutation involving bone marrow and paraspinal mass (myeloid sarcoma)

Case 239