Tissue stem cells and cancer stem cells: potential implications for gastric cancer

Gastric cancer remains the second leading cause of death in the world today, making the search for its molecular and cellular basis an important priority. Though recognition of the tight link between inflammation and tumorigenesis is centuries old, only recently are the pieces of the etiological puzzle beginning to fall together. Recent advances in gastric stem cell biology appear to be central to this slowly resolving puzzle. At least two types of stem cells may be important. Resident adult or tissue stem cells may, in a chronically inflamed environment, slowly acquire a series of genetic and epigenetic changes that lead to their emergence as 'cancer stem cells'. This scenario has not yet been proven experimentally, although the first step, prospective recognition of a gastric stem cell has recently been conquered. Alternatively, the setting of chronic inflammatory stress and injury may lead to loss of the indigenous gastric stem cells from their niches; bone marrow derived stem cells may then be recruited to and engraft into the gastric epithelium. Such recruited cells have the potential to contribute to the tumor mass. Indeed, evidence supporting this scenario has been published. Here, we review these recent findings and discuss implications for the future.     

A case of cutaneous symplastic leiomyoma - a rare variant of cutaneous pilar leiomyoma

We describe the case of a cutaneous symplastic leiomyoma in a 37-year-old woman who presented with a 4-year history of a painful slow growing lesion on the left upper arm. The lesion was excised and subjected to histological examination. A poorly circumscribed lesion was seen in the dermis composed of spindle shaped cells with marked nuclear pleomorphism. No mitotic figures or necrosis were seen. The cells stained strongly positive with desmin and smooth muscle actin, and negative with S100, melan A, MNF116 a mouse monoclonal antibody to cytokeratin and CK5/6. The diagnosis was felt to be in keeping with a cutaneous symplastic leiomyoma, a rarely reported variant of the pilar leiomyoma. Histologically, it shows features similar to the symplastic variant of uterine leiomyoma with cytological atypia, nuclear pleomorphism and minimal mitotic activity. Although the long-term outlook is probably benign, the presence of cytological atypia and mitoses in any spindle cell tumor is generally a concerning feature and warrants long-term follow up.     

Retroauricular milia en plaque: a rare presentation of lupus erythematosus

Milia en plaque is a term used to describe an aggregation of milia occurring on an erythematous base usually localized in the retroauricular area. In most reported cases, no aetiological factors have been identified. We report the first case of milia en plaque associated with discoid lupus erythematosus occurring in the retroauricular site.     

Somatosensory cortical activation identified by functional MRI in preterm and term infants

Functional MRI (fMRI) has not previously been used systematically to investigate brain function in preterm infants. We here describe statistically robust and reproducible fMRI results in this challenging subject group using a programmable somatosensory stimulus synchronized with MR image acquisition which induced well-localized positive blood oxygen level dependent (BOLD) responses contralateral to the side of the stimulation in: 11 preterm infants (median post menstrual age 33 weeks and 4 days, range 29 + 1 to 35 + 3); 6 control infants born at term gestational age; and 18 infants born preterm (median gestational age at birth 30 weeks and 5 days, range 25 + 4 to 36 + 0) but studied at term corrected gestational age. Bilateral signals were identified in 8 of the ex-preterm infants at term age. Anatomical confirmation of appropriate activations was provided with diffusion tensor imaging (DTI) based tractography which identified connecting pathways from the regions of activation through the ipsilateral corticospinal tracts and posterior limb of the internal capsule. These results demonstrate that it is possible to reliably identify positive BOLD signals in the infant brain and that fMRI techniques can also be applied in the study of preterm infants.     

Reduced or absent cyclin H expression is an independent prognostic marker for poor outcome in diffuse large B-cell lymphoma

Diffuse large B-cell lymphoma (DLBCL) is the most common lymphoid malignancy in adults, accounting for nearly 40% of all non-Hodgkin's lymphomas. As cell proliferation is essential for tumor growth, analysis of the cell cycle might give additional information on tumor progression. Although markers distinctive for cell-cycle regulation in DLBCL have been addressed, less attention has been paid to cyclin H in DLBCL with respect to its prognostic and potential therapeutic implications. Cyclin H occurs as a component of the cyclin H/Cdk 7/Mat 1 complex. Cyclin H is also a substrate of protein kinase 2, a ubiquitously expressed serine/threonine protein kinase required for cell viability and cell-cycle progression. We evaluated the expression of cyclin H by immunohistochemistry in 301 DLBCLs in a tissue microarray format. Validation was done by performing quantitative real-time polymerase chain reaction and Western blotting experiments for cyclin H. We studied the relationship between cyclin H expression in comparison to other cyclins (A, B1, D1, D3, and E) and the proliferation marker Ki-67. Reduced or absent cyclin H expression was seen in 14.5% of the DLBCL cases. Interestingly, reduced or absent cyclin H expression was correlated with lower expression of proliferation marker Ki-67 (P < .0001), cyclin B1 (P = .0001), cyclin D3 (P = .0007), and cyclin E (P < .0001). Reduced or absent cyclin H expression was significantly associated with poor overall survival, in both the univariate (P = .0286) and multivariate analysis with International Prognostic Index (P = .0180). Our study demonstrates the independent prognostic value of cyclin H expression in DLBCL and proposes its use as a prognostic marker.     

Clinicopathologic profile of 470 giant cell tumors of bone from a cancer hospital in western India

Over 20 years, 470 cases of giant cell tumor of bone diagnosed at a tertiary cancer hospital were analyzed. Male predominance (57%), predilection for bones around the knee joint (42%), and occurence in the 21- to 30-year-old age group (49.1%) with 6% being in the immature skeleton are well known facts. Accurate diagnosis was possible in 66% and 88% of cases on radiology and biopsy, respectively. Tumors measured 6 to 20 cm and, in 402 cases, showed “usual” histology comprising uniformly scattered multinucleate giant cells amidst mononuclear stromal cells, together imparting a syncitium-like appearance. Presence of osteoid, hemorrhage, and aneurysmal bone cyst–like areas; spindle cells in sheets (devoid of giant cells); or storiform pattern and intravascular osteoclasts were less common. The less common histologic features posed diagnostic difficulty in the setting of a small biopsy. Treatment included intralesional curettage (33.19%), marginal excision (4.2%), wide excision (31%), or radical surgeries (14.25%). Recurrences seen in 170 cases were multiple in 47 cases. Metastases largely to the lung were recorded in 24 cases. The histology of all the tumors, namely, primary, recurrent, or metastatic was identical. Statistical analysis using the computer software SPSS (SPSS Inc, Chicago, Ill)was performed with particular reference to the unusual histologic features vs recurrence and metastasis by χ² test. The only statistically significant factors were occurrence in the axial skeleton vs appendicular skeleton (P = .001) and primary treatment elsewhere vs at this hospital (P = .045), each of these being associated with increased frequency for local recurrence but not metastasis.     

Quantitative assessment of myocardial T2 relaxation times in cardiac amyloidosis

Purpose

To evaluate cardiac MRI (CMR) in the diagnosis of cardiac amyloidosis by comparing the T2 relaxation times of left ventricular myocardium in a pilot patient group to a normal range established in healthy controls.

Materials and Methods

Forty‐nine patients with suspected amyloidosis‐related cardiomyopathy underwent comprehensive CMR examination, which included assessment of myocardial T2 relaxation times, ventricular function, resting myocardial perfusion, and late gadolinium enhancement (LGE) imaging. T2‐weighted basal, mid, and apical left ventricular slices were acquired in each patient using a multislice T2 magnetization preparation spiral sequence. Slice averaged T2 relaxation times were subsequently calculated offline and compared to the previously established normal range.

Results

Twelve of the 49 patients were confirmed to have cardiac amyloidosis by biopsy. There was no difference in mean T2 relaxation times between the amyloid cases and normal controls (51.3 ± 8.1 vs. 52.1 ± 3.1 msec, P = 0.63). Eleven of the 12 amyloid patients had abnormal findings by CMR, eight having LGE involving either ventricles or atria and four demonstrating resting subendocardial perfusion defects.

Conclusion

CMR is a potentially valuable tool in the diagnosis of cardiac amyloidosis. However, calculation of myocardial T2 relaxation times does not appear useful in distinguishing areas of amyloid deposition from normal myocardium. J. Magn. Reson. Imaging 2009. © 2009 Wiley‐Liss, Inc.     

A pilot study of risk-adapted radiotherapy and chemotherapy in patients with supratentorial PNET

We undertook this study to estimate the event-free survival (EFS) of patients with newly diagnosed supratentorial primitive neuroectodermal tumor (SPNET) treated with risk-adapted craniospinal irradiation (CSI) with additional radiation to the primary tumor site and subsequent high-dose chemotherapy supported by stem cell rescue. Between 1996 and 2003, 16 patients with SPNET were enrolled. High-risk (HR) disease was differentiated from average-risk (AR) disease by the presence of residual tumor (M(0) and tumor size > 1.5 cm(2)) or disseminated disease in the neuraxis (M(1)-M(3)). Patients received risk-adapted CSI: those with AR disease received 23.4 Gy; those with HR disease, 36-39.6 Gy. The tumor bed received a total of 55.8 Gy. Subsequently, all patients received four cycles of high-dose cyclophosphamide, cisplatin, and vincristine with stem cell support. The median age at diagnosis was 7.9 years; eight patients were female. Seven patients had pineal PNET. Twelve patients are alive at a median follow-up of 5.4 years. The 5-year EFS and overall survival (OS) estimates for all patients were 68% +/- 14% and 73% +/- 13%. The 5-year EFS and OS estimates were 75% +/- 17% and 88% +/- 13%, respectively, for the eight patients with AR disease and 60% +/- 19% and 58% +/- 19%, respectively, for the eight with HR disease. No deaths were due to toxicity. High-dose cyclophosphamide-based chemotherapy with stem cell support after risk-adapted CSI results in excellent EFS estimates for patients with newly diagnosed AR SPNET. Further, this chemotherapy allows for a reduction in the dose of CSI used to treat AR SPNET without compromising EFS.     

M1 Medulloblastoma: high risk at any age

Background: The prognosis for children with M1 medulloblastoma (positive CSF cytology) has not been well-defined. Methods: We retrospectively reviewed the records of 285 newly diagnosed medulloblastoma patients treated between 1984 and 2006. Older children received post-operative craniospinal and tumor bed irradiation; radiotherapy for younger children depended on treatment era and physician/family preference. Results: 55 patients were <3 years old and 230 patients were ≥ 3 years old at diagnosis. We detected significant (P < 0.0001) associations between M1 disease and EFS for the entire cohort and for both younger and older patients. Among younger children, M1 patients had lower EFS than M0 (P = 0.0044). Conclusions: Children <3 years old with M1 medulloblastoma fared poorly in our small series. Survival for older children with M1 disease treated with higher-dose CSI was better than that of M2/M3 patients, but still less than optimal; our findings do not support reduction in therapy for either cohort.