Leukemia cutis - epidemiology, clinical presentation, and differential diagnoses

Leukemia cutis is an extramedullary manifestation of leukemia. The frequency and age distribution depend on the leukemia subtype. The clinical and morphological findings have a wide range of cutaneous manifestations and may present with nodular lesions and plaques. Rare manifestations include erythematous macules, blisters and ulcers which can each occur alone or in combination. Apart from solitary or grouped lesions, leukemia cutis may also present with an erythematous rash in a polymorphic clinical pattern. Consequently, leukemia cutis has to be distinguished from numerous differential diagnoses, i. e. cutaneous metastases of visceral malignancies, lymphoma, drug eruptions, viral infections, syphilis, ulcers of various origins, and blistering diseases. In the oral mucosa, gingival hyperplasia is the main differential diagnosis. The knowledge of the clinical morphology is of tremendously importance in cases in which leukemia was not yet known.     

Extramedullary acute leukemia developing in a pre‐existing osteoma cutis

Primary osteoma cutis (cutaneous ossification) is an uncommon disease in which there is bone formation within the skin in the absence of a demonstrable pre‐existing condition. Osteoma cutis is a chronic and benign condition. We report a case of a 45‐year‐old man who developed extramedullary acute leukemia with a myeloid immunophenotype (myeloid sarcoma) with its initial presentation within an isolated pre‐existing osteoma cutis in the post‐auricular scalp without evidence of systemic acute leukemia or chronic myeloid stem cell disorders. The tumor was surgically excised without complications. Four months later, acute leukemia recurred in the contralateral posterior mandible and showed an immunophenotype consistent with acute lymphoblastic leukemia/lymphoma. The patient now has been treated by standard protocols for acute leukemia. The diagnosis of an extramedullary acute leukemia is challenging because of its inconsistent clinical and histopathologic presentations. Extramedullary acute leukemia developing in a pre‐existing osteoma cutis is very unusual and has not been previously reported in the literature.     

Trisomy 8 in myeloid leukemia cutis confirmed by fluorescence in situ hybridization analysis

We present a case of a 64‐year‐old man with refractory acute myeloid leukemia and trisomy 8 who developed leukemia cutis. Interphase fluorescence in situ hybridization (FISH) was performed on a paraffin‐embedded skin section. FISH confirmed a population of cells with trisomy 8 in the blastic infiltrates involving the skin. This case illustrates a novel application of interphase FISH to confirm the diagnosis of leukemia cutis.     

Leukemia cutis in acute lymphocytic leukemia masquerading as viral exanthem.

Leukemia cutis is a specific skin lesion caused by infiltration of leukemic cells into the skin. It is uncommon in acute lymphocytic leukemia (ALL). It typically manifests as red or violaceous papules, nodules, or plaques, mainly on the face. Leukemia cutis presenting with a generalized viral exanthem-like maculopapular eruption appears to be rare in the English literature. We report such a case. A 19 year-old man presented with a generalized purpuric maculopapular eruption of eight day's duration. Hematologic studies showed changes of acute lymphocytic leukemia, T-cell type. A skin biopsy specimen revealed a cuff-like, dense, perivascular infiltration of atypical lymphocytes in the upper and mid-dermis, consistent with leukemia cutis. The rash resolved in two weeks after chemotherapy. Our case illustrates that leukemia cutis should be considered in the differential diagnosis of a generalized morbilliform viral exanthem-like eruptions. Skin biopsy is important in establishing the diagnosis.     

A case of symmetrical leukemia cutis on the eyelids complicated by B-cell chronic lymphocytic lymphoma

We describe herein a case of symmetrical bilateral leukemia cutis on the eyelids, especially on the lower lids, in a patient with B-cell chronic lymphocytic leukemia (CLL). The patient was a 63-year-old Japanese man who had been diagnosed with CLL. Eyelid swelling is well known to result from local skin or systemic diseases including tumors, hyperthyroidism, nephritic syndrome, and hypoalbuminemia. To our knowledge, symmetrical, bilateral, flesh-colored leukemia cutis on the eyelids has not been previously reported.     

A Case of Congenital Leukemia Cutis

Congenital leukemia is a rare disease that develops from birth to 6 weeks of life. Leukemia cutis involves cutaneous infiltration by leukemic cells and is an unusual manifestation of leukemia, and has been documented in 25~30% of patients with congenital leukemia. The authors report a case of congenital leukemia cutis. A newborn male presented with widespread firm dusky red papules and nodules on almost his entire body surface. Skin biopsy specimens confirmed the presence of leukemic infiltrations, and bone marrow cytology was consistent with acute myeloid leukemia of the FAB M5 type.     

皮肤白血病1例

患者，男性，22岁。1999年5月出现发热，经血液和骨髓穿刺证实为急性骨髓性白血病M5型（急性单核细胞性白血病）。2000年2月行自身外周血干细胞移植并顺利植活。移植后4个月患者发现前胸部出现紫红色结节、斑块，组织病理为“继发皮肤白血病”，骨髓穿刺和皮损免疫组化诊断为“急性骨髓白血病M5型复发”。经10天化疗，患者皮损减轻。     

皮肤白血病特异性皮损与病情演变预后分析

分析了皮肤白血病特异性皮损与病情的演变预后，选择24例皮肤白血病患者（10例皮肤白血病为特异性皮损，14例皮肤白血病为非特异性皮损）进行临床，病理，实验室和细胞免疫学分类等综合分析，将有特异性皮损的患者病情演变过程及预后转归与未发生特异性皮损的皮肤白血病患者进行比较，并做统计学处理，结果白血病患者发生特异性皮损，病情处于进展加重状态，预后较未发生特异性皮损的白血病患者差，两者之间有显著性差异，表明皮肤白血病患者出现特异性皮损提示病情加重，肿瘤在广泛转移，有迅速发展死亡的危险，应及时有效治疗控制病情。     

A dystrophic calcinosis cutis case treated with CO2 laser

Abstract

Calcinosis cutis is the deposition of insoluble calcium salts within cutaneous tissue. It may be divided into four major subtypes: dystrophic, metastatic, idiopathic, and iatrogenic. The most common subtype is dystrophic calcinosis cutis. It can occur as a result of local tissue injury. We herein present a child with dystrophic calcinosis cutis developed following trauma and successfully treated with CO₂ laser.     

Plaque-like osteoma cutis with transepidermal elimination

Osteoma cutis is a rare lesion that consists of the presence of bone tissue within the dermis and/or hypodermis. It may be classified as primary osteoma cutis, when bone tissue develops in the skin without any pre-existing lesion and secondary osteoma cutis, which is more frequent and occurs when osseous tissue develops on a pre-existing lesion. We present a case of primary plaque-like osteoma cutis involving the scalp, left forehead and left cheek, which appeared in an adult male. Histopathological study showed several islands of mature osseous tissue involving the full thickness of the dermis. In some areas, there was also transepidermal elimination of bone spicules. We review the literature about previously reported similar cases.     

Differentiation syndrome during ivosidenib treatment with immunohistochemistry showing isocitrate dehydrogenase R132H mutation

We report a case of differentiation syndrome in a patient receiving the IDH1 inhibitor ivosidenib, with skin biopsy showing isocitrate dehydrogenase (IDH) R132H-mutated leukemia cutis. A 72-year-old man with IDH1-mutated acute myeloid leukemia (AML), status-post allogeneic cell transplantation, on ivosidenib for 6 months, was admitted for culture-negative neutropenic fever, pink and purpuric plaques and patches on the legs, abdomen and back, edema, hypotension, and shortness of breath. Skin biopsy revealed an infiltrate of atypical, immature, myeloperoxidase-positive mononuclear cells compatible with leukemia cutis or Sweet syndrome. Although dermal edema and interstitial neutrophilic infiltrate with karyorrhexis characteristic of Sweet syndrome were not seen, the atypical cells lacked expression of CD117 and CD34, which were expressed in the original leukemia. Additional immunohistochemical staining of suspected blasts was strongly positive for IDH1 R132H, suggesting a diagnosis of leukemia cutis. As the immunophenotype of blasts in skin infiltrates can significantly differ from the immunophenotype seen in blood and bone marrow, this case shows that mutation-specific antibodies such as anti-IDH1 R132H may be useful to help distinguish malignant from non-malignant infiltrates in the skin. Furthermore, differentiation syndrome may show histopathologic features of leukemia cutis on skin biopsy.     

Aplasia cutis congenita with precancerous transformation - the first case. Why do these scars never develop invasive tumors?

The term aplasia cutis congenita characterizes a heterogeneous group of diseases which have in common a focal absence of the skin. The defect may be limited to the epidermis but often involves the full thickness of the skin including the underlying bone. At birth the lesions present as erosive patches and they heal rather rapidly with a residual scar. Although more than 200 publications on aplasia cutis congenita have appeared in the medical literature between 1966 and 1999, surprisingly no case of malignant degeneration has been described. We observed a 58-year-old male patient with aplasia cutis congenita who developed crusted changes within the scar over the past 10 years. Repeated biopsies over the years have always documented a precancerous lesion without solar elastosis. Invasion has never been observed in this patient. We hypothesize that for invasive malignancies dermal-epidermal interactions are necessary. Such a cell to cell communication seems to be impossible in patients with aplasia cutis congenita, as the dermal-epidermal unit is not developed. Aplasia cutis congenita might serve as an interesting model for further investigations on the importance of epidermal-dermal interactions.     

Cutaneous presentation preceding acute myeloid leukemia with CD4+/CD56+ expression misdiagnosed as a blastic plasmocytoid dendritic cell neoplasm: A case report

Acute myeloid leukemia (AML) may initially present as cutaneous lesions corresponding to blasts involving the skin as the first clinical manifestation prior to blood and bone marrow (BM) infiltration. Such presentation is known as myeloid leukemia cutis (LC). Blastic plasmocytoid dendritic cell neoplasm (BPDCN) is an aggressive tumor derived from the precursors of plasmocytoid dendritic cells with cutaneous and BM involvement and leukemic dissemination. Myeloid LC and BPDCN may be difficult to distinguish as they share similar clinical and histopathological features, in particular AML with monocytic differentiation. Nevertheless, the correct diagnosis has to be made to determine adequate and effective therapy. Here, we report the case of a 61‐year‐old woman who presented with an AML with MLL rearrangement and CD4+/CD56+ expression presenting as LC and that was misdiagnosed as BPDCN. We emphasize that careful and exhaustive analyses should be performed to make the correct diagnosis.     

Angioinvasive Fusarium and concomitant Enterococcus infection arising in association with leukemia cutis

Leukemia cutis represents the cutaneous infiltration of neoplastic leukocytes or their precursors that results in clinically identifiable skin lesions. For patients with myelodysplastic syndrome, developing such a lesion may indicate impending leukemic transition. These patients are also often immunocompromised, putting them at risk for infection by opportunistic fungal pathogens such as Fusarium. We describe an 85-year-old man with myelodysplastic syndrome who presented with a reddish-purple nodule with a surrounding erythematous plaque on his shin. Histopathologic examination revealed a dense diffuse infiltrate of large atypical cells in the reticular dermis, with ulceration and necrosis. Immunohistochemical studies showed positive staining with CD15, CD68 and myeloperoxidase of constituent large cells. Concurrently, there were branching and septate hyphae with occasional macroconidia-like structures throughout the infiltrate. Cultures from this lesion grew Fusarium and Enterococcus, supporting the diagnosis: leukemia cutis with superinfection involving both Fusarium and Enterococcus. To our knowledge, this is a novel report of two separate infections occurring in a lesion of leukemia cutis. This case shows that in patients with a hematologic malignancy and skin lesions, a high index of suspicion for infection is necessary when reviewing both the clinical and histopathological data to avoid overlooking an important occult infectious agent.     

Acute myelomonocytic leukemia revealed by a chickenpox-like rash

An unusual case of leukemia cutis is presented. A 42-year-old man presented with a vesicular skin rash mimicking chickenpox. Skin biopsy firmly ruled out the diagnosis of varicella and revealed an infiltration of the superficial derma by myeloblasts. Bone marrow aspirates confirmed the diagnosis of acute myelomonocytic leukemia (type M4).     

Incidental finding of cutaneous meningeal heterotopia in aplasia cutis congenita

Aplasia cutis congenita and cutaneous meningeal heterotopia are both rare congenital conditions that most commonly occur on the scalp and may appear clinically and histologically similar. A subtype of aplasia cutis congenita, membranous aplasia cutis congenita, and cutaneous meningeal heterotopia are both proposed to result from neural tube closure errors. However, neither non‐membranous nor membranous aplasia cutis congenita are known to occur together with cutaneous meningeal heterotopia in the same lesion. We report the incidental finding of cutaneous meningeal heterotopia within a lesion of aplasia cutis congenita.     

A Case of Congenital Leukemia Cutis

Congenital leukemia is a rare condition diagnosed at birth to 6 weeks of life with an estimated incidence of 4.7 per million live births. In a review, about 25~30% of cases were well documented as leukemia cutis. We report a case of a 3-month-old infant presented with asymptomatic multiple erythematous to bluish patches and nodules, which had developed about two months ago. Biopsy of the cutaneous lesions revealed immature cells which are overall monotonous with large kidney shaped nucleus, prominent nucleoli and moderate cytoplasm. These atypical cells stained positive for leukocyte common antigen, lysozyme and CD68. With this result, a congenital leukemia cutis was diagnosed. Six months later, she underwent cord blood stem cell transplantation. Seven months after the cord blood stem cell transplantation, the bone marrow examination revealed a normal result. Leukemia can be presented in the skin, the eruption may be nonspecific and it may precede systemic involvement. The recognition is important because early diagnosis can lead to appropriate treatment, followed by better prognosis.     

Unilateral aplasia cutis congenita on the leg

We present the case of a newborn male with aplasia cutis congenita on the extensor side of the right leg, with unilateral absence of skin on the lower limb. There was no abnormality in pregnancy or birth and there was no associated malformation or skin disease such as blistering or nail pathology. The management of this large ulcer was conservative, using silver sulfadiazine ointment, and healing occurred within 3 months. The follow-up after 21 months showed little scar formation and no handicap regarding function and appearance. The psychomotor development was normal. According to the classification outlined by Frieden, we classified this condition as type VII aplasia cutis congenita.     

Leukemia cutis presenting as localized cutaneous hyperpigmentation

The usual clinical presentations of leukemia cutis include solitary infiltrated erythematous or violaceous plaques or nodules and multiple localized or generalized papules. On the other hand, cutaneous hyperpigmentation is a frequent finding in patients with malignancies, most of the cases because of chemotherapy or other drugs that the patient is taking. We present a case of cutaneous hyperpigmentation as the presenting sign of leukemia cutis. A 61-year-old male presented with cutaneous hyperpigmentation, which had appeared during the last chemotherapy cycle for treatment for biphenotypic leukemia. Cutaneous lesions consisted of bluish to brownish irregular well-defined discoloration of the skin involving the upper part of the trunk and the temporal regions of the forehead. The patient was asymptomatic and the skin was not infiltrated at all. However, histopathologic study showed nodular infiltrates involving the full-thickness of the dermis and destroying pre-existing adnexa. This infiltrate was composed of atypical basophilic cells with large hyperchromatic nuclei and scant cytoplasm. Immunohistochemical studies showed intense immunoexpression for CD43, CD68, CD45RO and myeloperoxidase within these cells. A diagnosis of biphenotypic leukemia cutis was established. In our review of the literature we have not found any report of cutaneous hyperpigmentation as the presenting manifestation of leukemia cutis.     

Disseminated linear calcinosis cutis associated with the Koebner phenomenon in an infant with congenital acute monocytic leukaemia

We present a unique case of an infant with acute monocytic leukaemia who presented at birth with multiple rubbery, erythematous to violaceous subcutaneous nodules secondary to leukaemia cutis. As these infiltrates regressed with chemotherapy, numerous white to yellow linear confluent papules appeared in a scratch-like pattern. These lesions were widely disseminated but were concentrated across her face, trunk and extremities with relative sparing of the napkin area and back. We propose that these lesions represent a form of dystrophic calcinosis cutis that occurred secondary to koebnerization in an infant with congenital leukaemia cutis.