Stromal invasion pattern identifies patients at lowest risk of lymph node metastasis in HPV-associated endocervical adenocarcinomas, but is irrelevant in adenocarcinomas unassociated with HPV.

OBJECTIVE: The Silva invasion pattern-based classification system stratifies endocervical adenocarcinomas (ECAs) into 3 categories corresponding to risk of metastasis and recurrence, but has only been evaluated for HPV-associated ECAs of usual type. We examined whether the Silva system is applicable to all endocervical adenocarcinomas, especially those not associated with HPV. METHODS: Complete slide sets from 341 surgical specimens of ECA were collected from 7 institutions worldwide. All specimens were associated with clinical records covering at least 5 years of follow-up. Tumors were classified as HPV-associated (HPVA) or not (NHPVA) by both morphology and detection of HPV using in situ hybridization. Recurrence and survival were analyzed by multivariate Mantel-Haenszel methods. RESULTS: Most specimens (292; 85.6%) were HPVA, while 49 (14.3%) were NHPVA. All NHPVAs were Silva pattern C, while 76.0% of HPVAs were pattern C, 14.7% pattern A, and 9.3% pattern B. Including both HPVAs and NHPVAs, lymphovascular invasion (LVI) was detected in 0% of pattern A, 18.5% of pattern B and 62.6% of pattern C cases (p < 0.001). None of the pattern A or B cases were associated with lymph node metastases (LNM), in contrast to pattern C cases (21.8%). Among patients with Silva pattern C ECA, those with HPVA tumors had a lower recurrence rate and better survival than those with NHPVA; however, when adjusted for stage at diagnosis, the difference in recurrence and mortality was small and not statistically significant. CONCLUSIONS: Application of the Silva system is only relevant in HPVA cervical adenocarcinoma.

Localization of luteinizing hormone receptor protein in the human ovary.

The luteinizing hormone receptor (LHR) plays a pivotal role during follicular development. Consequently, its expression pattern is of major importance for research and has clinical implications. Despite the accumulated information regarding LHR expression patterns, our understanding of its expression in the human ovary, specifically at the protein level, is incomplete. Therefore, our aim was to determine the LHR protein localization and expression pattern in the human ovary. We examined the presence of LHR by immunohistochemical staining of human ovaries and western blots of mural granulosa and cumulus cells aspirated during IVF treatments. We were not able to detect LHR protein staining in primordial or primary follicles. We observed equivocal positive staining in granulosa cells and theca cells of secondary follicles. The first appearance of a clear signal of LHR protein was observed in granulosa cells and theca cells of small antral follicles, and there was evidence of increasing LHR production as the follicles mature to the pre-ovulatory stage. After ovulation, LHR protein was ubiquitously produced in the corpus luteum. To confirm the expression pattern in granulosa cells and cumulus cells, we performed western blots and found that LHR expression was stronger in granulosa cells than in cumulus cells, with the later demonstrating low, but still significant, amounts of LHR protein. In summary, we conclude that LHR protein starts to appear on granulosa cells and theca cells of early antral follicles, and low but significant expression of LHR exists also in the cumulus cells. These results may have implications for the future design of clinical protocols and culture mediums for in vitro fertilization and especially in vitro maturation of oocytes.

A phase II clinical and pharmacodynamic study of temsirolimus in advanced neuroendocrine carcinomas.

Standard cytotoxic treatments for neuroendocrine tumours have been associated with limited activity and remarkable toxicity. A phase II study was designed to evaluate the efficacy, safety and pharmacodynamics of temsirolimus in patients with advanced neuroendocrine carcinoma (NEC). Thirty-seven patients with advanced progressive NEC received intravenous weekly doses of 25 mg of temsirolimus. Patients were evaluated for tumour response, time to progression (TTP), overall survival (OS) and adverse events (AE). Twenty-two archival specimens, as well as 13 paired tumour biopsies obtained pretreatment and after 2 weeks of temsirolimus were assessed for potential predictive and correlative markers. The intent-to-treat response rate was 5.6% (95% CI 0.6-18.7%), median TTP 6 months and 1-year OS rate 71.5%. The most frequent drug-related AE of all grades as percentage of patients were: fatigue (78%), hyperglycaemia (69%) and rash/desquamation (64%). Temsirolimus effectively inhibited the phosphorylation of S6 (P=0.02). Higher baseline levels of pmTOR (phosphorylated mammalian target of rapamycin) (P=0.01) predicted for a better response. Increases in pAKT (P=0.041) and decreases in pmTOR (P=0.048) after treatment were associated with an increased TTP. Temsirolimus appears to have little activity and does not warrant further single-agent evaluation in advanced NEC. Pharmacodynamic analysis revealed effective mTOR pathway downregulation.

Accelerated usual interstitial pneumonitis, anti-DNA antibodies and hypocomplementemia.

A healthy 60-year-old patient presented with progressive dyspnoea. Clinical, radiographic and pathological features of interstitial lung disease were found and an open lung biopsy established the diagnosis of usual interstitial pneumonitis (UIP) (idiopathic pulmonary fibrosis). Despite treatment, the patient died 4 months later in respiratory failure. Although the patient had no extra-thoracic involvement at autopsy, his illness was associated with a very high titre of anti-double-stranded DNA antibodies, hypocomplementemia, hypergammaglobulinaemia and lymphoid hyperplasia. These features and a literature review, suggest immune-mediated lung damage in a subset of patients with UIP.

[Nephrogenic adenoma--benign lesion of urinary tract system].

Nephrogenic adenoma is a rare metaplastic benign lesion of the urinary tract caused by chronic irritation to the urinary epithelium. The appearance of this lesion is usually characterized by hematuria and irritative symptoms. Nephrogenic adenoma may be found most commonly in the bladder and the urethra and less frequently in the renal pelvis and ureters. We present 5 patients who underwent surgery due to bladder or urethral nephrogenic adenoma. Despite the fact that nephrogenic adenoma is a benign lesion, long term follow-up is needed due to the high recurrence rate and the potential, though rare, malignant transformation.

Psammomatous melanotic schwannoma: presentation of a rare primary lung tumor.

A 30-year-old nonsmoking man underwent a left lower lobectomy with bronchoplasty for an obstructing lesion of the left lower lobe. Pathology results demonstrated a psammomatous melanotic schwannoma, a rare pigmented neural tumor of which only 25 cases have been reported as originating in the respiratory tract.

The amyloid deposit in calcifying epithelial odontogenic tumor is immunoreactive for cytokeratins.

Calcifying epithelial odontogenic tumor, also known as Pindborg tumor, is a rare benign tumor with locally aggressive behavior. It is characterized by squamous epithelial cells, calcifications, and eosinophilic deposits that have been identified as amyloid. We report a case of calcifying epithelial odontogenic tumor and investigate the nature of the amyloid, using histologic, immunohistochemical, and ultrastructural studies. The amyloid was immunohistochemically negative for basement membrane components and positive for all cytokeratin stains performed (cocktail of cytokeratins 1, 5, 6, 8, 13, and 16, and cytokeratins AE1 and AE3). The amyloid stained focally in a glandular-like pattern, reminiscent of the epithelial glandlike structures of the tumor. We conclude that the amyloid is derived from filamentous degeneration of keratin filaments that originate from the tumor squamous epithelium. The keratin degeneration is part of a developmental or aging process that the tumor undergoes.

Brown tumour of hyperparathyroidism in the mandible associated with atypical parathyroid adenoma.

The brown tumour of hyperparathyroidism is a localized bone tumour and an uncommon manifestation of hyperparathyroidism. A 27-year-old woman presented with a mandibular 8 x 10 cm solid mass diagnosed as central giant cell granuloma. Chemical blood analysis revealed increased serum calcium levels of 12.46 mg/dL and the parathyroid hormone level was 124 pg/dL. The patient underwent surgery with removal of a parathyroid mass. Histologically, this parathyroid tissue was seen to be limited by a fibrous capsule with morphological features consistent with atypical parathyroid adenoma. The mandibular tumour has receded and the patient declined further procedures. This is the first case reported of brown tumour as the primary manifestation of an atypical parathyroid adenoma, a lesion that shares some features with parathyroid carcinoma without the unequivocal properties of malignancy.

Positive antineutrophil cytoplasmic antibodies-associated vasculitis presenting with hemoptysis and a mediastinal mass.

A patient with end-stage renal failure, due to IgA nephropathy, was found to have a mediastinal mass. Biopsy specimen of the mass showed a necrotizing vasculitis. Antineutrophil antibodies to myeloperoxidase were strongly positive. To our knowledge, no case of a mediastinal mass due vasculitis has been reported in the literature, and our observation should lead to broadening of the spectrum of clinical manifestations of vasculitis.