Effective use of mirtazapine for refractory pruritus associated with carcinoma en cuirasse.

Pruritus is a debilitating symptom that can be associated with cutaneous involvement by an underlying malignancy. We report the case of a 68-year-old woman with a history of triple-negative breast cancer who presented with extensive, localised cutaneous metastasis complicated by incapacitating, treatment-refractory pruritus localised to the anatomic regions involved by her metastatic disease. Physical examination revealed an indurated, ecchymotic, ulcerated plaque circumferentially encasing her thorax. Histopathological examination revealed substantial dermal lymphatic involvement and dilation as well as dermal collagen infiltration by tumour cells and nodules. The clinical and pathological findings were consistent with a diagnosis of carcinoma en cuirasse. Mirtazapine, a noradrenergic antidepressant with antiserotonin and antihistamine activity, was started and led to rapid, sustained relief of the patient's pruritus. Mirtazapine may be a useful systemic agent for the palliative relief of pruritus associated with cutaneous infiltration by an underlying malignancy.

Stem cells and targeted approaches to melanoma cure.

Melanoma stem cells, also known as malignant melanoma-initiating cells, are identifiable through expression of specific biomarkers such as ABCB5 (ATP-binding cassette, sub-family B (MDR/TAP), member 5), NGFR (nerve growth factor receptor, CD271) and ALDH (aldehyde dehydrogenase), and drive melanoma initiation and progression based on prolonged self-renewal capacity, vasculogenic differentiation and immune evasion. As we will review here, specific roles of these aggressive subpopulations have been documented in tumorigenic growth, metastatic dissemination, therapeutic resistance, and malignant recurrence. Moreover, recent findings have provided pre-clinical proof-of-concept for the potential therapeutic utility of the melanoma stem cell concept. Therefore, melanoma stem cell-directed therapeutic approaches represent promising novel strategies to improve therapy of this arguably most virulent human cancer.

The multidrug-resistance transporter ABCB5 is expressed in human placenta.

ATP-binding cassette (ABC) transporters in placenta protectively transport drugs and xenobiotics. ABCB5 [subfamily B (MDR/TAP)] is a novel ABC multidrug-resistance transporter that also mediates cell fusion, stem cell function, and vasculogenic plasticity. Immunohistochemistry and double-labeling immunofluorescence staining for ABCB5 and ABCB5/CD200, respectively, was performed on formalin-fixed, paraffin-embedded placental tissue from 5 first trimester, 5 second trimester, and 5 term pregnancies as well as 5 partial moles, and 5 complete moles. In addition, tumor cells from 5 choriocarcinoma and 5 placental site trophoblastic tumor cases were examined. ABCB5 staining was observed in villous trophoblasts in 100% (5/5) of first trimester placentas (with progressive decrease in term placentas); 100% of partial moles (5/5); and 100% of complete moles (5/5). Notably, reactivity was discretely restricted to the inner trophoblast layer, with no staining of overlying syncytiotrophoblast. Antibody specificity and localization was confirmed further by in situ hybridization. ABCB5 expression was retained in 20% of choriocarcinomas (1/5) and 40% of placental site trophoblastic tumors (2/5). Prior studies have localized expression of multidrug-resistance-1, also known as ABCB1, within the syncytiotrophoblast of early placentas, where it serves a protective function as an efflux transporter. Our results show that ABCB5 is preferentially expressed in the cytotrophoblast layer of placental villi. The expression of this novel biomarker at the maternal-fetal interface raises questions on its role in placental structure and function as well as on its potential contribution to the protective efflux provided by other P-glycoprotein transporters.

Metastatic basal cell carcinoma of the posterior neck: case report and review of the literature.

Although primary basal cell carcinoma (BCC) represents an extremely common malignancy, metastases derived from BCC are exceedingly rare. The prognosis for metastatic BCC is poor, and little consensus exists regarding predictive factors or optimal treatment strategies. Here, we present the case of a 63-year-old man with BCC of the neck who subsequently developed multiple metastases to subcutaneous tissue, lymph nodes, and the parotid gland. Risk factors and clinical features of metastatic BCC are reviewed, as is the relationship of histopathologic subtype to metastatic behavior. Current chemotherapeutic and targeted therapies also are discussed in the context of recent advances in molecular biology.

Panniculitis associated with dermatomyositis and recurrent ovarian cancer.

BACKGROUND: Panniculitis is a rare cutaneous manifestation of dermatomyositis (DM), typically presenting as tender, erythematous subcutaneous nodules. Complications, such as pain, calcinosis, and lipoatrophy, are associated with high morbidity. While it has been suggested that panniculitis in DM may correlate with a better prognosis, our understanding of its true significance, prognostic implications, and management is limited by the paucity of reported cases. We describe the first reported case to our knowledge of DM-associated panniculitis in the setting of ovarian adenocarcinoma as well as in association with a recurrent malignancy. OBSERVATIONS: A 63-year-old woman with a history of DM and recurrent ovarian adenocarcinoma presented with multiple painful, erythematous subcutaneous nodules on the bilateral upper arms, thighs, and buttocks. Histologic examination showed lymphoplasmacytic panniculitis with associated dermal mucin deposition, consistent with lobular panniculitis in association with connective-tissue disease. Treatment with oral methotrexate resulted in sustained clinical improvement over a 10-month period. CONCLUSIONS: Although panniculitis in DM has previously been suggested to be a good prognostic indicator, our case report describes an association with ovarian adenocarcinoma and a recurrent malignancy. Methotrexate may be an effective treatment for panniculitis in DM.

Hidradenitis suppurativa resulting in systemic amyloid A amyloidosis: a case report and review of the literature.

Hidradenitis suppurativa is a chronic, inflammatory disease of the follicular epithelium that presents as tender, subcutaneous nodules in an intertriginous distribution with sinus tract formation. Most commonly, hidradenitis suppurativa results in local complications, such as scarring and infection. However, systemic complications, such as anemia and arthropathies, have also been described. Herein, we report an unusual case of systemic amyloid A secondary to hidradenitis suppurativa. We describe a 39-year-old man with a long history of recurrent, tender, erythematous nodules in the axillary and anogenital regions, resulting in abscesses, sinus tract formation, and large areas of scarring. After 21 years of cutaneous disease with concurrent elevated systemic inflammatory markers, the patient was noted to have significant proteinuria. A kidney biopsy and immunostaining revealed deposits of amyloid A. Echocardiogram and electrocardiogram showed ventricular and atrial wall thickening with an appearance consistent with cardiac amyloid deposition. Systemic amyloid A amyloidosis is a serious, but rare, complication of chronic inflammatory disorders, including hidradenitis suppurativa, with potential multi-organ involvement including renal and cardiac manifestations. Amyloid A amyloidosis should be suspected in patients with chronic inflammatory cutaneous diseases who present with renal abnormalities, especially proteinuria or the nephrotic syndrome.

SOX2 contributes to melanoma cell invasion.

The mechanisms of melanoma invasion are poorly understood despite extensive inquiry. SRY (sex determining region Y)-box 2 (SOX2) is an embryonic stem cell transcription factor that has recently been discovered to be expressed in human melanoma where it is associated with dermal invasion and primary tumor thickness. To assess the potential role of SOX2 expression in melanoma invasion, we examined patient melanomas and humanized melanoma xenografts, and noted preferential SOX2 expression in cells that interfaced and infiltrated dermal stroma. Experimental knockdown (KD) of SOX2 mRNA and protein in A2058 melanoma cells with high constitutive SOX2 expression resulted in 4.5-fold decreased invasiveness in vitro compared with controls (P<0.0001). Conversely, when G361 cells that normally express low SOX2 were transduced to overexpress SOX2 mRNA and protein, a 3.8-fold increase in invasiveness was observed (P=0.0004). Among 84 invasion-related genes, RT-PCR screening revealed that SOX2 KD resulted in striking decrease in matrix metalloproteinase-3 (MMP-3), an endopeptidase associated with cleavage of the extracellular matrix. Quantitatively, SOX2 KD diminished MMP-3 mRNA by 87.8%. MMP-3 KD in SOX2-expressing A2058 cells served to inhibit invasion, although to a lesser degree than SOX2 KD. Finally, immunostaining of patient and xenograft melanomas revealed coordinate SOX2 and MMP-3 expression in regions of stromal infiltration. These data implicate SOX2 expression in melanoma invasion, and suggest a role for MMP-3 as one potential mediator of this process.

Melanoma stem cells: not rare, but well done.

Since the identification of self-renewing cells in the hematopoietic system, stem cells have transformed the study of medicine. Cancer biologists have identified stem-like cells in multiple malignancies, including those of solid organs. This has led to the development of a stem cell theory of cancer, which purports that a subpopulation of self-renewing tumor cells is responsible for tumorigenesis. This contrasts with the stochastic model of tumor development, which advances that all tumor cells are capable of tumor formation. Within the field of melanoma, the identity and existence of cancer stem cells has been the subject of recent debate. Much of the controversy may be traced to differences in interpretations and definitions related to the cancer stem cell theory, and the use of dissimilar methodologies to study melanoma cells. Accumulating evidence suggests that cancer stem cells may exist in melanoma, although their frequency may vary and they may be capable of phenotypic plasticity. Importantly, these primitive melanoma cells are not only capable of self-renewal and differentiation plasticity, but also may confer virulence via immune evasion and multidrug resistance, and potentially via vasculogenic mimicry and transition to migratory and metastasizing derivatives. Therapeutic targeting of melanoma stem cells and the pathways that endow them with virulence hold promise for the design of more effective strategies for amelioration and eradication of this most lethal form of skin cancer.