The mitosis-specific marker phosphohistone-H3 (PHH3) is an independent prognosticator in uterine smooth muscle tumours: an outcome-based study.

AIMS: Accurate mitosis counting, which is important in the diagnosis of uterine smooth muscle tumours (USMTs), is often difficult and subjective. The mitosis-specific immunohistochemical marker phosphohistone-H3 (PHH3) has been shown to be diagnostically useful, but its expression, in relation to outcome, has not been thoroughly investigated. The aim of this study is to evaluate PHH3 as a diagnostic and prognostic marker in USMTs. METHODS AND RESULTS: PHH3 expression was evaluated in 55 leiomyosarcomas (LMSs), 26 smooth muscle tumours of uncertain malignant potential (STUMPs), 18 leiomyomas with bizarre nuclei (LBN), and 12 leiomyomas (LMs). Scores were expressed as counts per 10 high-power fields (HPFs). Median follow-up durations of patients with LMS, STUMP, LBN and LM were, respectively, 39, 78, 65.5 and 49.5 months. Twenty-eight patients with LMSs (50.9%) died, and two (7.7%) patients with STUMPs experienced recurrence. The median PHH3 scores for LMSs were significantly higher than those for other categories of tumour. A score of ≥29/10 HPFs was also independently associated with a poor outcome. To test whether the PHH3 score could distinguish between benign USMTs with atypical histology and those that were clinically malignant, two biological groups were further delineated. Patients in group 1 (18 LBNs and 24 STUMPs) all had an uneventful outcome, whereas patients in group 2 (two recurrent STUMPs and 32 LMSs) all had a recurrence or tumour-related death. Median PHH3 scores for the two groups were, respectively, 2/10 HPFs and 27/10 HPFs. A PHH3 score of ≥7/10 HPFs was highly associated with malignancy. CONCLUSION: PHH3 is useful in evaluation of the biological behaviour of USMTs, and may serve as a prognostic indicator for LMSs.

Kidney allograft failure due to acute phosphate nephropathy associated with severe secondary hyperparathyroidism.

Intratubular calcification is a common finding in renal allografts. However, possible harmful effect of this calcification is not well recognized, and allograft failure purely due to this condition has not been reported. We report a kidney transplant recipient who suffered from severe secondary hyperparathyroidism and unexplained early allograft failure. A diagnosis of acute phosphate nephropathy was made subsequently based on serial allograft biopsy findings. This case calls for a high index of suspicion to look for this rare cause of allograft dysfunction among high-risk patients. It also highlights the importance of good calcium-phosphate control before renal transplantation.

Idiopathic cervical fibrosis--a new member of IgG4-related sclerosing diseases: report of 4 cases, 1 complicated by composite lymphoma.

Idiopathic cervical fibrosis is a rare tumefactive inflammatory-sclerosing lesion involving the soft tissues of the head and neck, and a proportion of patients also have synchronous or metachronous inflammatory fibrosclerosing lesions in other anatomic sites. The latter finding suggests that this entity may represent a member of IgG4-related sclerosing diseases. We report 4 cases to support this postulation. The patients were male adults aged 42 to 89 years, who presented with an infiltrative, firm cervical mass. Two patients also had IgG4-related chronic sclerosing sialadenitis of submandibular gland and lymphadenopathy. Histologically, the cervical soft tissue lesions had ill-defined borders, consisting of coalescent nodular lymphoid aggregates accompanied by a sclerotic stroma. Nerve infiltration, skeletal muscle invasion, and phlebitis were present. There was a significant increase in IgG4 plasma cells (87 to 327 per high-power field, with IgG4/IgG ratio of 63% to 98%). In the soft tissue lesion of 1 patient, there were expansile foci comprising dense sheets of plasma cells and small lymphoid cells that exhibited κ light chain restriction and clonal immunoglobulin gene rearrangement, consistent with supervening extranodal marginal zone lymphoma. The adjacent lymph node from the same patient showed Epstein-Barr virus (EBV)-positive classical Hodgkin lymphoma with typical morphology and immunophenotype (CD30, CD15, PAX5). Thus lymphoma can supervene in the chronic inflammatory background similar to that recently documented for IgG4-related sclerosing disease of the ocular adnexa.

Inflammatory pseudotumors of the central nervous system.

Inflammatory pseudotumor is a disease with unsettled pathogenesis. The brain is a rare site of occurrence. The aim of this study is to investigate ALK-1 protein expression and IgG4-positive plasma cells detection in 4 intracranial inflammatory pseudotumors. Three dural-based and 1 intraventricular inflammatory pseudotumors were retrieved from the hospitals' archive. The data on clinical presentation, radiological findings, procedure undertaken, and patients' progress were collected. Sections from the excised lesions were examined under hematoxylin and eosin, histochemical, and immunohistochemical staining including ALK-1 and IgG4. All 4 cases displayed typical histological features of inflammatory pseudotumor with dense lymphoplasmacytic infiltrate admixed with small number of benign-looking spindle cells in a collagenous stroma. Three cases exhibited high density of IgG4-positive plasma cells per high-power field. ALK-1 was negative. ALK expression was not found in any of our cases. On the contrary, the detection of significant number of IgG4-positive plasma cells in 3 inflammatory pseudotumors suggests that a considerable proportion of intracranial inflammatory pseudotumor may belong to the IgG4-related subgroup. Hence, a trial of corticosteroid after histological confirmation may be valid to avoid unnecessary risk-taking neurosurgical procedures or in cases with incomplete tumor removal.