Melanoma metastatic to “lipomata”

Three patients presented with solitary melanoma metastases that mimicked a simple “lipomata.” On further investigation each patient had a discrete fatty tissue tumor mass surrounding a melanoma metastasis. The presence of an enlarging mass in patients with a history of melanoma should be viewed with suspicion and a biopsy should be performed.     

Resistance to “Castration‐Resistant”

The author challenges the use of the phrase “castration resistance,” which is widely used in the literature and also appears in a recent article by Merseburger et al.In a recent article in The Oncologist, Merseburger et al. [1] outline perspectives arising from current progress in the treatment of advanced prostate cancer (PC). As a nonspecialist in this area, I found their account effectively addresses the challenges posed by this difficult clinical problem. However, I take this opportunity to challenge in turn the widely used phrase “castration resistance.”More than half a century ago, it was established that growth of PC was reduced by bilateral orchiectomy [2], and the rough term “castration” was commonly used. Then it was found that a similar therapeutic effect could be achieved alternatively by the administration of hormone-related agents such as diethylstilbestrol or goserelin [3]: such approaches became known as “chemical castration” (but the adjective was often dropped). Because the growth of PC (just as the development of the normal prostate itself) depends on androgens through androgen-receptor (AR) signaling, there was a sound rationale for these therapeutic procedures of androgen deprivation, frequently called more loosely “hormonal treatments.”Unfortunately, however, all of these beneficial interventions proved time-limited, as PC eventually resumes growth: one might have presumed that it had become independent of AR signaling. However, it transpired that things were not that simple. In an authoritative paper [4] published in 2004, the evidence was reviewed that when PC relapses after hormonal treatment, AR signaling is still on, due to two possible explanations: (a) androgens had not been completely eliminated (they are produced by the adrenal glands and sometimes by the PC itself); (b) even in complete absence of the androgen ligand, AR signaling can still operate through devious means (including AR mutation/amplification, crosstalk-mediated activation of other signaling pathways, and other mechanisms [4, 5]). From then on, the phrase “castration-resistant PC” (CRPC) became popular (n = 1,795 in PubMed).Perhaps the time has come to abrogate this term. First, from the clinical point of view for patients who have CRPC, there are now different remedies available depending on whether the resistance results from (a) or (b) above (e.g., abiraterone versus enzalutamide); thus, the term may cause confusion rather than clarity. Second, we should restore dignity to both patients and terminology. It was a disrespectful mistake in the past to indulge in the phrases “castration” and “chemical castration.” CRPC is worse, and I have even come across the variant “castration-resistant patients,” which some patients perceive as an accusation of refusing to accept something to which unfortunately they have been already subjected. One oncologist told me he used to use the term “castration resistance” freely, but, having PC himself, he has now changed his mind. Instead of CRPC, he suggests, for the two above-mentioned types, respectively, (a) “androgen-deprivation-resistant PC due to persistence of residual androgen” and (b) “androgen-depletion-resistant PC due to androgen-independent persistence of AR signaling.” I admit that these phrases are a bit cumbersome. More simply, androgen deprivation-resistant PC and androgen depletion-resistant PC could both be covered by ADRPC (and they could be called ADPRC-a, ADPRC-b), but the choice of appropriate acronyms is best left to the experts.     

“FISHing” to detect urinary and other cancers

BACKGROUND:

The UroVysion Bladder Cancer Kit detects amplifications of chromosomes 3, 7, and 17, and the deletion of 9p21, by fluorescence in situ hybridization (FISH). Because manual interpretation of UroVysion FISH is time consuming and can be challenged by variable probe signal strengths and background labeling, the authors investigated an automated image analysis system to improve throughput, productivity, quality control, and accuracy.

METHODS:

The authors evaluated the interactive BioView Duet imaging system as an aid to UroVysion FISH interpretation in a 2‐armed, blinded comparison with manual screens of the same 135 consecutive cases. Manual and Duet‐assisted interpretations were compared with respect to concordance, reproducibility, and timing.

RESULTS:

Eighty‐one cases were interpreted as positive or negative with 94% concordance and a kappa value of 0.84 between manual and Duet‐aided interpretations. Three cases that ultimately were judged positive were detected with the aid of Duet but were missed with a manual screen. A final interpretation could not be given for≈25% of Duet‐scanned cases. Duet‐aided interpretation was highly reproducible for patient and control slides. Pathologist evaluation time per case was 4 minutes compared with 30 minutes for manual interpretation. Cytotechnologist involvement added 18 minutes for a total of 22 minutes, a savings of 8 minutes per case.

CONCLUSIONS:

Duet‐aided interpretations were at least equivalent to manual interpretations. The system permitted interactive review of abnormal cells and had the ability to evaluate the same cells for brightfield cytology followed by FISH. The image processing and analysis tools of the Duet system enhanced the morphology skills of cytology professionals in providing accurate interpretations. Cancer (Cancer Cytopathol) 2010. © 2010 American Cancer Society.     

Breast-cancer incidence in relation to height,weight and body-fat distribution in the Dutch “DOM” cohort

In a cohort of 11,663 participants in a breast-cancer screening program, height, weight, waist circumference and hip circumference were measured, and information about menstrual and reproductive history was obtained by questionnaire. After exclusion of 83 women with unclear menopausal status, the subjects were divided into 3 sub-cohorts: 5,891 women who were pre-menopausal at the time of data collection, 3,521 women who had entered the study after natural menopause, and 2068 women who had been hysterectomized and/or ovariectomized. After a median follow-up of 10.6 years, 147, 76 and 52 incident cases of breast cancer were detected in the 3 respective sub-cohorts. No statistically significant association was found in any of the sub-cohorts between breast-cancer risk and height, weight, body-mass index (BMI) or hip circumference. In the sub-cohort of women with natural menopause, however, risk of breast cancer was positively and significantly associated with the ratio of waist-to-hip circumferences (WHR) (RR = 2.63 for upper vs. lower quartile), and this association did not change after adjustment for variations in disease risk related to body height and weight. Although similar to observations in other cohort studies showing positive associations between obesity and breast-cancer risk in post-menopausal women, our results are different, in that WHR and not BMI appears to be the more specific indicator of breast-cancer risk. Int. J. Cancer 76:647–651, 1998.© 1998 Wiley-Liss, Inc.     

Platelets in cancer metastasis: To help the “villain” to do evil

Cancer progress is accompanied by platelet activation and thrombotic complications. Platelets are a dangerous alliance of cancer cells, and are a close engager in multiple processes of cancer metastasis. Platelet adhesion to cancer cells forms a protective cloak that helps cancer cells to escape immune surveillance and natural killer cell‐mediated cytolysis. Platelets facilitate tethering and arrest of disseminated cancer cells in the vasculature, enhance invasive potentials and thus extravasation of cancer cells. Moreover, platelets recruit monocytes and granulocytes to the sites of cancer cell arrest, and collaborate with them to establish a pro‐metastatic microenvironment and metastatic niches. Platelets also secret a number of growth factors to stimulate cancer cell proliferation, release various angiogenic regulators to regulate tumor angiogenesis and subsequently promote cancer growth and progress. Albeit platelets are helping the “villain” cancer to do evil, the close engagements of platelets in cancer metastasis and progress can be used as the intervention targets for new anti‐cancer therapeutic developments. Platelet‐targeted anti‐cancer strategy may bring in novel anti‐cancer treatments that can synergize the therapeutic effects of chemotherapies and surgical treatments of cancer.