58
T. Tadmor & A. Polliack
case reports, and their prevalence is probably under- estimated, as autopsy data tend to suggest [4]. Among some of the other reports on the uncommon complications and presentations of HCL [5] is an extensive review chapter on the topic written by Van Den Neste and colleagues in 1988 [6], which summarized the unusual manifestations of the dis- ease in a larger series of cases, as well as another shorter review by Polliack in 2002 dealing with these aspects of HCL in a briefer manner [7]. Other rare associations have mostly been collected from the reports of anecdotal cases as well as from personal experience gained from clinical practice over many years. Some of the sites of involvement of disease are difficult to summarize with certainty, because autopsy reports have shown that ‘so called’ rare sites ‘may in fact be more common than clinicians realize.’ [4]. Furthermore, it is not always easy to determine whether some of the rare associations are indeed coincidental or truly linked or specifically associated with HCL. The atypical morphological forms of HCL and the
expression of unusual phenotypes encountered in HCL cells are not included in this short summary, and what has been referred to as the ‘Japanese variant of HCL’ is not discussed here [8]. Many of the unusual findings are summarized in
Table I. From the reported data it is evident that bulky
abdominal lymphadenopathy and the presence of mediastinal lymph nodes were encountered in about 15% of patients with advanced disease, when computed tomography (CT) was used as part of the investigation for HCL [6]. These findings are usually seen and indicative of progressive and resistant disease, and rarely associated with the presence of ascites (even chylous) and pleural effusions [6]. Skeletal lesions, most frequently osteolytic in
nature, occur in 0–13% but basically in about 3% of patients and may be painful, appearing mostly in the long bones and axial skeleton. Diffuse osteo- sclerosis as well as demineralization and osteoporosis
Table I. Unusual sites of disease.
. Bulky abdominal lymphadenopathy . Tumor masses in mediastinum . Paravertebral masses . Painful skeletal lytic lesions . Pleural effusion and ascites . Skin lesions . Ocular-corneal involvement, uveitis, retinal artery thrombosis . Neurological-meningeal and CNS cord compression . Gastrointestinal: esophageal, gastric, protein losing enteropathy . Hepatic involvement: heptomegaly, tumor masses, simulating ‘hepatitis’ cavernous hemangiomata
CNS, central nervous system.
may also occur, while mixed patterns may also be observed [2,9,10]. Collapse of vertebrae and com- pression and fractures of the head of the femur may also be observed, and when severe fibrosis or osteosclerosis is evident, primary myelofibrosis and secondary fibrosis relating to other hematological disorders must be excluded clinically. In some patients myeloma and other secondary tumors must be excluded from the differential diagnosis because they can also occur as coexistent disorders in HCL. In the modern era of imaging, magnetic resonance imaging (MRI) and positron emission tomography (PET)-CT are more sensitive methods to detect and distinguish these disorders today (Table II). Cutaneous manifestations [11] are variable and are
difficult to establish with certainty, as these are mostly based on retrospective data and biopsies were not always performed. Cutaneous lesions are infre- quently specific HCL infiltrates (possibly only 2– 14% of skin lesions: leukemia cutis), and there is a wide range of cutaneous lesions that may occur; some of these are listed in Table III. These include ‘paraneoplastic’ phenomena ranging from vasculitis and scleroderma to infections [11,12]. Rare gastrointestinal involvement with documen-
ted HCL infiltration occurs. [3,6,7], while ocular manifestations and involvement including panuveitis have been described [13], as well as an isolated patient with retinal artery obstruction due to asso- ciated gammopathy [6]. Very rare examples of isolated central nervous and meningeal involvement with neurological findings, radicular infiltration, and tumor invasion of the cord, with cord compression resulting from vertebral tumor involvement, have all been reported as anecdotal cases [6,7,14,15]. Unusual clinical manifestations may also include
liver involvement by HCL with hepatomegaly, as part of progressive or untreated advanced disease, with a
Table II. Bone lesions.
. Osteolytic lesions, demineralization, and osteoporosis . Axial skeleton and long bones involvement . Spontaneous fractures and pain . Diffuse osteosclerosis . Mixed patterns of bone lesions . Responsive to radiotherapy and chemotherapy
Table III. Cutaneous lesions.
. Mostly non leukemic . Maculopapular rashes . Fasciitis, cellulitis . Infections, Pyoderma gangrenosum . Vasculitis . Sweet syndrome . Vitiligo and scleroderma
Page 1 |
Page 2 |
Page 3 |
Page 4 |
Page 5 |
Page 6 |
Page 7 |
Page 8 |
Page 9 |
Page 10 |
Page 11 |
Page 12 |
Page 13 |
Page 14 |
Page 15 |
Page 16 |
Page 17 |
Page 18 |
Page 19 |
Page 20 |
Page 21 |
Page 22 |
Page 23 |
Page 24 |
Page 25 |
Page 26 |
Page 27 |
Page 28 |
Page 29 |
Page 30 |
Page 31 |
Page 32 |
Page 33 |
Page 34 |
Page 35 |
Page 36 |
Page 37 |
Page 38 |
Page 39 |
Page 40 |
Page 41 |
Page 42 |
Page 43 |
Page 44 |
Page 45 |
Page 46 |
Page 47 |
Page 48 |
Page 49 |
Page 50 |
Page 51 |
Page 52 |
Page 53 |
Page 54 |
Page 55 |
Page 56 |
Page 57 |
Page 58 |
Page 59 |
Page 60 |
Page 61 |
Page 62 |
Page 63 |
Page 64 |
Page 65 |
Page 66 |
Page 67 |
Page 68 |
Page 69 |
Page 70 |
Page 71 |
Page 72 |
Page 73 |
Page 74 |
Page 75 |
Page 76 |
Page 77 |
Page 78 |
Page 79 |
Page 80 |
Page 81 |
Page 82 |
Page 83 |
Page 84 |
Page 85 |
Page 86 |
Page 87 |
Page 88 |
Page 89 |
Page 90 |
Page 91 |
Page 92 |
Page 93 |
Page 94 |
Page 95 |
Page 96 |
Page 97 |
Page 98 |
Page 99 |
Page 100 |
Page 101 |
Page 102 |
Page 103 |
Page 104 |
Page 105 |
Page 106 |
Page 107 |
Page 108 |
Page 109 |
Page 110 |
Page 111 |
Page 112 |
Page 113 |
Page 114 |
Page 115 |
Page 116 |
Page 117 |
Page 118 |
Page 119 |
Page 120 |
Page 121 |
Page 122