Karl Sotlar

An elderly woman presented with anaemia, thrombocytopenia and multifocal lytic and sclerotic bone lesions. Trephine bone marrow biopsy demonstrated widespread involvement by systemic mastocytosis (SM). The neoplastic mast cells expressed mast cell tryptase, CD117, CD25 and CD9, and were accompanied by compact sheets of atypical large histiocytic cells, expressing CD68, CD4, S-100 protein and CD14, in keeping with a concomitant histiocytosis (SM-AHNMD). Mutation analysis revealed the activating point mutation D816V of the c-kit proto-oncogene in microdissected pooled bone marrow mast cells. Partial remission was achieved using interferon alpha. To the best of our knowledge this is the first reported case of SM-AHNMD with histiocytosis as the non-mast cell component.

Inflammatory pseudotumor (IPT) is a rare benign lesion, often imitating a malignant disease. An IPT was found in the sinus piriformis of a 40-year-old male who suffered from dysphagia, globus feeling and a weight loss of 5 kilograms in six months. Neither common infections previously described in combination with IPT such as human herpes virus (HHV) 8, human immunodeficiency virus (HIV) or acute Epstein Barr virus (EBV), nor evidence of manifestation of a systemic mastocytosis or a malignant disease were found. The primary therapy for IPT in locations other than the orbita is complete resection, if this is not applicable or recurrence occurs then cyclosporine, chlorambucil, indometacin or radiation have been used as alternative treatments. A transoral laser-assisted resection was performed in the case described here, resulting in a complete and lasting cure.

A nested multiplex PCR (NMPCR) assay that combines degenerate E6/E7 consensus primers and type-specific primers was evaluated for the detection and typing of human papillomavirus (HPV) genotypes 6/11, 16, 18, 31, 33, 35, 39, 42, 43, 44, 45, 51, 52, 56, 58, 59, 66, and 68 using HPV DNA-containing plasmids and cervical scrapes ( n = 1,525). The performance of the NMPCR assay relative to that of conventional PCR with MY09-MY11 and GP5+-GP6+ primers, and nested PCR with these two primer sets (MY/GP) was evaluated in 495 cervical scrapes with corresponding histologic and cytologic findings. HPV prevalence rates determined with the NMPCR assay were 34.7% (102 of 294) in the absence of cervical intraepithelial neoplasia (CIN 0), 94.2% (113 of 120) in the presence of mild or moderate dysplasia (CIN I/II), and 97.8% (44 of 45) in the presence of severe dysplasia (CIN III). The combination of all four HPV detection methods applied in the study was taken as “gold standard”: in all three morphological subgroups the NMPCR assay had significantly ( P < 0.0001) higher sensitivities than the MY09-MY11 and GP5+-GP6+ assays and sensitivities comparable or equal to those of the MY/GP assay. All 18 HPV genotypes investigated were detected among the clinical samples. The ratio of high- to low-risk HPV genotypes increased from 4:1 (80 of 103) in CIN 0 to 19:1 (149 of 157) in CIN I to III. Multiple infections were detected in 47.9% (124 of 259) of the patients. In conclusion, the novel NMPCR method is a sensitive and useful tool for HPV DNA detection, especially when exact HPV genotyping and the identification of multiple HPV infections are required.

In the vast majority of patients with systemic mastocytosis (SM), the bone marrow is the primary extracutaneous site of disease. In addition to bone marrow involvement, other visceral organs such as the spleen, liver or the gastrointestinal tract, may also be affected. However, isolated involvement of a single extramedullary organ is rarely seen in SM. We report on two patients with SM with splenic involvement, lack of ‘diagnostic’ mast cell (MC) infiltrates in the bone marrow, and absence of skin lesions. In one patient, a myelodysplastic syndrome was diagnosed prior to the detection of SM. Both patients presented with massive splenomegaly and multifocal MC infiltrates in splenic tissues. These MCs also expressed CD25 as well as the C-KIT mutation D816V. In consecutive examinations, the mutation was also detected in the bone marrow in both patients suggesting diffuse infiltration with neoplastic cells. In summary, our data show that the spleen can be a primary site of disease in rare cases of SM. Mastocytosis should therefore be considered as a (rare) differential diagnosis in patients with splenomegaly of unknown etiology.

The term mastocytosis denotes a heterogeneous group of rare hematological disorders characterized by abnormal accumulation of mast cells. While cutaneous mastocytosis is relatively frequent mast cell leukemia belongs to the rarest forms of human leukemia. In the following we present the case of an aleukemic mast cell leukemia and shall discuss the revised classification of mastocytosis based on the "Year 2000 Working Conference on Mastocytosis" held in Vienna, Austria. A 48 year-old caucasian man presented with a four-week history of diarrhea, obstipation, vomiting, rash, and mild fever. Clinical inspection revealed a disseminated itching rash and a mild hepatomegaly. Red and white blood cell counts were within the normal range. Levels of the alkaline phosphatase and serum histamine were significantly increased. There was no splenomegaly or lymphadenopathy. Cytologic and histologic investigation of the bone marrow revealed a marked increase in atypical mast cells. Since only a few circulating mast cells could be detected in a cytospin preparation of the blood, the diagnosis of an aleukemic mast cell leukemia was established. About four weeks after the diagnosis had been established, the patient died with signs of a hemorrhagic shock due to a massive gastrointestinal bleeding. Autopsy revealed widespread mast cell infiltration of bone marrow, spleen, liver and lungs, but also a small, deeply penetrating, non-specific duodenal ulcer. In conclusion, despite of presentation with signs of a primary gastrointestinal disorder, the patient was found to suffer from an exceedingly rare aleukemic mast cell leukemia ("malignant mastocytosis") and died after a total duration of the disease of only about three months.