Diffuse, fracturing systemic skeletal histiocytosis of unknown type: a novel metabolic bone disease.

We describe a novel disease of diffuse skeletal histiocytosis associated with multiple fragility fractures and high osteoclast activity. Clinical, radiographic, biochemical, genetic, and histopathological investigations were performed to characterize the diagnosis of an Asian man who presented with hip fracture and diffuse skeletal lytic lesions. After excluding malignancy and other common metabolic bone diseases, open bone biopsy yielded several pathological samples all showing extensive skeletal histiocytosis likely to explain the diffuse axial and appendicular lytic lesions. Rare disorders such as Langerhans histiocytosis, Erdheim-Chester disease, and diffuse cystic skeletal angiomatosis were excluded through careful pathological examination and lack of CD1a and S-100 staining. Whole exome sequencing did not yield diagnostic findings to explain this likely acquired disease. High markers of osteoclast activity suggested excessive focal bone resorption but normalized after zoledronic acid treatment. A novel disease of skeletal histiocytosis with high bone turnover is differentiated from other histiocytic and lytic skeletal diseases.

Preoperative chemoradiation and flap reconstruction provide high local control and low wound complication rates for patients undergoing limb salvage surgery for upper extremity tumors.

BACKGROUND AND OBJECTIVES: Neoadjuvant protocols in the management of upper extremity sarcoma have improved local control rates but have been associated with high complication rates. We present a refinement of the Eilber protocol using judicious preoperative chemoradiation, limb salvage surgery, and flap coverage to achieve high local control rates with acceptable wound healing complications. METHODS: Patients presenting with upper extremity neoplasms from 1986 to 2002 were treated with a modified Eilber protocol, consisting of 3 days of adriamycin (30 mg/day) and sequential radiotherapy (300 cGy/day for 10 days). Limb salvage surgery with flap coverage where needed was performed 4-8 weeks later. Patients were followed prospectively for recurrence. RESULTS: Fifty-three consecutive patients with upper extremity tumors were treated and followed for a mean of 6.1 years. This cohort included 44 sarcomas and nine non-metastasizing, locally aggressive tumors. There were two local recurrences (3.8%). Limb salvage was achieved in all patients. Flaps were required in 43.4% of patients. Major complications occurred in 11%, were all flap related (partial flap loss, venous congestion), and went on to heal promptly with treatment. CONCLUSION: This modified Eilber protocol achieved 96% local control for upper extremity tumors with a wound complication rate of 11%. The liberal use of flaps of resulted in healed, stable wounds in all patients.

Use of tissue expanders and pre-operative external beam radiotherapy in the treatment of retroperitoneal sarcoma.

INTRODUCTION: We report our experience of treating retroperitoneal sarcoma (RPS) using pre-operative external beam radiotherapy (EBRT) in combination with radical resectional surgery from 1990 to 2005. METHODS: Twenty-eight primary and 10 recurrent tumors were identified from a prospective database. RESULTS: The resection rate was 71% overall; 82% in primary (23/28) and 40% (4/10) in recurrent cases. EBRT was administered preoperatively in 25 patients, postoperatively in 1, and palliatively in 11. In 33 patients a saline-filled tissue expander was inserted into the abdomen before radiotherapy to displace small bowel from the radiation field. 4,500-5,000 cGy was administered in fractions of 180-200 cGy over a 5-week period; surgery followed 6-8 weeks later. Expander insertion was associated with minimal morbidity; 31/37 patients received a dose of 4,000 cGy or more (median 4,650 cGy). Median resected tumor diameter was 13 cm, and a median of three adjacent organs was resected per patient. Complete macroscopic resection was achieved in 25/27 patients (93%); R0 in 9 (33%) and R1 in 13 (48%) (microscopic margins unclear in 5). There was no postoperative mortality. Tumors were high-grade in 20 patients, low-grade in 14 and ungraded in 4. Actuarial 5- and 10-year survival for all patients was 74 and 60%. For operable primary tumors, the 5-year survival and disease-free rates were 90 and 80%. In four patients with operable recurrent tumors, median disease-free interval was 91 months (27-160). In the 11 inoperable cases, median survival after radiotherapy was 48 months (9-77). CONCLUSIONS: We conclude that a combination of pre-operative tissue expander placement, high-dose EBRT and radical resectional surgery can achieve acceptable morbidity, extended survival and low long-term recurrence in patients with RPS. STATISTICS: Median (interquartile range).

Carcinoid syndrome symposium on treatment modalities for gastrointestinal carcinoid tumours: symposium summary.

OBJECTIVE: To develop a collaborative approach for the treatment of gastrointestinal carcinoid tumours and carcinoid syndrome. PARTICIPANTS: Leaders in the medical, endocrine, radiologic and surgical treatment of carcinoid disease were selected to present papers at the Carcinoid Syndrome Symposium on Treatment Modalities for Gastrointestinal Carcinoid Tumours and participate in the workshop that followed. EVIDENCE: A multidisciplinary symposium with experts in the field of carcinoid syndrome was organized at the University of Calgary. Data presented, participation of the attendees and a review of the literature were used in the workshop to develop a collaborative approach to the management of carcinoid tumours. BENEFITS: Carcinoid tumours are rare and few centres have large experiences in their treatment. Before the development of this collaboration, patients with carcinoid tumours received a unidisciplinary approach depending on referral patterns. The development of a multidisciplinary neuroendocrine clinic helped to unify the approach to these patients, yet a consensus on the treatment of carcinoid tumours was lacking. The expertise at the symposium allowed for consensus and the development of treatment algorithms, including biochemical screening, radiographic localization and surgical intervention, for gastrointestinal carcinoid tumours. The role of medical and hormonal therapy after cytoreducion is presented. RECOMMENDATION: Patients with carcinoid tumours require a multidisciplinary approach to their care.

Laser capture microdissection-guided fluorescence in situ hybridization and flow cytometric cell cycle analysis of purified nuclei from paraffin sections.

Laser capture microdissection (LCM) has recently been identified as a quick, simple, and effective method by which microdissection of complex tissue specimens for molecular analysis can be routinely performed. Assessment of gene copy number by fluorescence in situ hybridization (FISH) is useful for the analysis of molecular genetic alterations in cancer. Unfortunately, the application of FISH to paraffin sections of tumor specimens is fraught with technical difficulty and potential artifacts. Our results demonstrate that LCM-microdissected nuclei are suitable for FISH gene copy analysis. Amplification of genes in cancer specimens can be detected as easily in LCM-prepared nuclei as in fresh nuclei from cancer tissue specimens. Furthermore, contamination of tumor specimens by normal cells can make interpretation of flow cytometric cell cycle analysis difficult. Our results show that LCM-microdissected nuclei can also be used for flow cytometric cell cycle and ploidy analysis. LCM/FISH offers the advantages of multicolor FISH in a morphologically defined cell population, without the technical problems of FISH performed on paraffin sections. This technique should further simplify the methodology required to perform copy number analysis of tumor suppressor or protooncogenes in archived cancer specimens. The use of LCM specimens will also improve the specificity and simplify the interpretation of flow cytometric cell cycle and ploidy analysis of breast cancer specimens.

Is primary CNS lymphoma really becoming more common? A population-based study of incidence, clinicopathological features and outcomes in Alberta from 1975 to 1996.

BACKGROUND: The incidence of primary CNS lymphoma (PCNSL) is believed to be increasing in immunocompetent patients but this may not be universally true. The objective of this study was to determine in a population if the incidence of PCNSL is increasing, if the histologic subtypes are changing, and to describe the clinicopathologic and outcome characteristics of PCNSL. PATIENTS AND METHODS: We identified all Alberta residents with a histologic diagnosis of PCNSL from 1 January 1975 to 31 December 1996 using the Alberta Cancer Registry. Annual age-standardized incidence rates (ASIR), clinicopathologic and outcome characteristics were determined. RESULTS: There were 50 immunocompetent PCNSL patients; the median age was 64 and 30 were male. Their median survival was 10.15 months. Histology was available for review in 37 (74%) patients: 19 (51%) were diffuse large cell, 16 (43%) were immunoblastic and 2 (5%) were unclassifiable malignant lymphomas. The ASIR ranged from 0.178-1.631/10(6) and no change in ASIR was found (test for trend, P = 0.26) for gender or age. The ASIR of malignant gliomas did not change either but increased for all other non-Hodgkin's lymphoma (94.95-138.7610(6); test for trend, P = 0.0001) The number of brain biopsies increased from 1979-1985 (test for trend, P < 0.0001) but remained stable from 1986-1996 (test for trend, P = 0.99). CONCLUSIONS: Unlike several other populations, PCNSL is not becoming significantly more common in Alberta. If this difference is real (i.e., not due to differences in cancer registry coding practices etc.) comparisons between Albertans and other populations in whom the incidence is rising may provide clues regarding the etiology of PCNSL.

Hypopigmentation of a papillary carcinoma arising in a black thyroid.

We report a case of an unpigmented papillary carcinoma arising in a black thyroid induced by minocycline. Black thyroid syndrome is an unusual pigmented change seen almost exclusively in patients on minocycline, apparently resulting from an oxidative interaction between thyroid peroxidase and the drug. Twenty-six cases have previously been reported in the English literature, nine of which described an associated thyroid neoplasm. Four of these nine neoplasms were described as pale or hypopigmented. The nature of the lesion against the background of pigmentation suggests diminished function of the thyroid peroxidase in this clonal population.

Characteristics of the snoring noise in patients with and without occlusive sleep apnea.

We analyzed snoring noise from 10 nonapneic heavy snorers and nine patients with obstructive sleep apnea (OSA). Sound was recorded simultaneously through two microphones, one attached to the manubrium sterni and one suspended in the air 15 cm from the patient's head. Signals were stored on magnetic tape, digitized, and displayed in the time and frequency domains. Most of the power of snoring noise was below 2,000 Hz, and the peak power was usually below 500 Hz. When snores were generated during nose-only breathing (nasal snores), the sound spectrum was made up of a series of discrete, sharp peaks, with a fundamental note and harmonics similar to the spectrum of voiced sounds. When snores were generated during breathing through nose and mouth (oronasal snores), the spectra showed a mixture of sharp peaks and broad-band white noise. Patients with apnea showed a sequence of snores with spectral characteristics that varied markedly through an apnea-respiration cycle. The first postapneic snore consisted mainly of broad-band white noise with relatively more power at higher frequencies, so that the ratio of power above 800 Hz to power below 800 Hz could be used to separate snorers from patients with OSA. Other breaths in the cycle resembled oronasal or nasal snores in nonapneic subjects. Characteristics of the noise give information about the possible mechanism of sound generation and thus about the behavior of the pharynx during snoring. Quality of snoring sound may help to separate patients with obstructive apnea from those with simple snoring.