Koebner’s phenomenon as a rare mechanism of acute myeloid leukemia dissemination: report of two cases with a brief overview

Excerpt

Koebner’s phenomenon (KP) [1, 2] is represented by a skin alteration induced by several kinds of nonspecific trauma such as burn scars, surgical wounds [3], injections, and so on. Associations with numerous systemic disorders [4], including malignancies of the hematopoietic system [5‐9], have been reported. In the latter setting, this issue is scarcely understood and probably underestimated. The placement of central venous catheter (CVC) as causative mechanism of KP has not been reported so far. Therefore, we thereby describe this very unusual occurrence as recently observed by us in two patients with acute myeloid leukemia (AML). The first case regarded a 56-year-old woman who was diagnosed on March 2009 as having an AML (FAB M1, karyotype 46, XX t (6;9) (p23;q34), Dek/Kan rearrangement positive) probably secondary to cytotoxic treatments given because of an endometrial sarcoma. The patient received induction chemotherapy (CHT) according to the 3 + 7-day regimen consisting of daunorubicin and cytarabine; a tunneled single-lumen CVC was placed in the right internal jugular vein before the start of treatment. Two weeks after the start of anti-AML treatment, an extensive infection involving the CVC exit site and the near corresponding soft tissue occurs. The lesion (Fig. 1) resulted in a large erythematous infiltrative papular lesion. Blood cultures were negative; systemic antimicrobial therapy (piperacillin/tazobactam plus teicoplanin) was started, and the CVC was promptly removed; the CVC tip analysis was negative. After the initial antimicrobial therapy, the lesion failed to improve and, thus far, a second-line therapy with meropenem, linezolid, and liposomial amphotericin B was commenced. A slow and incomplete improvement was achieved. A cutaneous biopsy of the lesion revealed a prominent perivascular and periadnexal cuffs of myeloperoxidase-positive myeloid blast, associated with the infiltration of inflammatory cells (Fig. 1), thus suggesting the diagnosis of leukemia infiltration in the context of infection-related tissue damage. At day +25, a bone marrow (BM) aspirate revealed the persistence of AML for which the patient, who was considered ineligible for a second-line CHT, was offered oral hydroxiurea with a palliative intent. To date, 6 months after the initial AML diagnosis, the patient is alive and the skin lesion is stable. The second observation concerned the case of a 52-year-old woman with a diagnosis of AML (FAB M1; Karyotype 46, XX; molecular biology AML1/ETO, CBF beta/MYH11, BCR/ABL; DEK/KAN; FLT3, NPM1 negative), which was made on April 2009 Similar to the first case, even in this patient, a tunneled single-lumen CVC was placed in right internal jugular vein before induction CHT, consisting of daunorubicin, cytarabine, and etoposide, by which a complete remission was achieved. On day +46, she presented with cervicobrachialgia associated with clinical signs (skin ema and induration) of an infected CVC, which was promptly removed. Systemic antimicrobial therapy with piperacillin/tazobactam and teicoplanin was empirically started, so that the infection will slowly be resolved. Due to the persistence of cervicobrachialgia, a nuclear magnetic resonance (NMR) was performed, revealing a leukemia relapse (cervical spine cord compressing leukemia localization). A second-line CHT was then started; however, on day +45, the morphological examination of a BM aspirate revealed a refractory disease; a further NMR demonstrated a more massive extramedullary involvement. Few days later, the patient developed a large papular infiltrative subclavian soft tissue lesion, originating from the exit site of the previously removed CVC; after the failure of the initial antimicrobial therapy, the patient undergone a skin biopsy which revealed a diffuse interstitial, perivascular, and periadnexal infiltration by atypical medium-sized cells with irregular nuclei, finely disperse chromatin, small nucleoli, and thin rime of clear cytoplasm. Immunochemistry demonstrated the following immunophenotype: CD43+, MPO+/−, CD34−, CD79 alpha, and CD3−; proliferation index, evaluated with Ki67 (MIB1), was 95–100%. These features were indicative of a skin infiltration by a population of immature myeloid cells (leukemia cutis). On August 2009, a salvage regimen according to the FlAIda, including fludarabine, cytosina arabinoside, and idarubicin, was then administered achieving a complete regression of the skin lesion, but at day +30, a BM aspirate demonstrated a massive involvement by AML. The patient rapidly deteriorated until her death supervened 5 months after the initial AML diagnosis. Skin complications may portray a significant burden of sufferance and hamper the optimal disease management in affected patients with AML which very rarely may exert a koebnerization capacity, usually involving the site of previous skin damage [7‐9]. Such propensity of myeloblasts may be interpreted as a deviation from normal cellular function of myeloid cells, usually able to migrate into tissue following chemotaxis signaling originated by cellular damage, represented in our cases by the CVC placement. The few cases here reported permit to hypothesize a similar mechanism involved in other tissue lesions such as lung, liver, or central nervous system infiltrates, commonly determined by infectious agents, but potentially supported or bordered by neoplastic infiltration. The practical suggestion to clarify with histological examination any suspicious lesion (e.g., antimicrobial unresponsiveness of even proven infectious infiltrates) may be propose, thus avoiding, in a potentially substantial proportion of patients, the disastrous mistake to consider untreatable a potentially sensitive disease localization.

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