Initial presentation of acute myelogenous leukemia in the infiltrate underlying an actinic keratosis.

We report an 85-year-old female patient who presented with an erythematous keratotic lesion on her temple suspicious of squamous cell carcinoma. Histological evaluation revealed actinic keratosis, but the underlying atypical infiltrate contained atypical myeloid forms consistent with acute myelogenous leukemia (AML). Upon further questioning, it was determined that the patient had a history of myelodysplastic syndrome. Her skin biopsy provided the first evidence of progression to AML. This case serves as an important reminder of the role the dermatopathologist plays in identifying serious systemic disease.

Tufted hemangioma: clinical case and literature review.

Tufted hemangiomas are relatively rare benign vascular proliferations that are congenital or appear during the first years of life. Herein we present an additional case of tufted hemangioma that appeared one year after birth and discuss its histopathological criteria and differential diagnosis with malignant vascular proliferations including sarcoma Kaposi, angiosarcoma and kaposiform hemangioendothelioma.

Anaplastic large cell lymphoma: a potential pitfall in the differential diagnosis of melanoma.

The diagnosis of metastatic melanoma can be complicated by absent characteristic cytology, melanin, or antigen expression in a suspect tumor, putting the pathologist at risk for incorrectly diagnosing recurrent melanoma while missing a second malignancy. We report a 69-year-old man with a history of acral melanoma, metastatic to inguinal nodes, presenting with an ipsilateral thigh nodule. Histology showed a proliferation of pleomorphic cells in the dermis and subcutis, suspicious for melanoma. S100, Melan-A, and HMB-45 immunohistochemistry were negative. However, microphthalmia-associated transcription factor and CD117 labeled the neoplasm, prompting consideration of a late metastatic melanoma with loss of antigen expression. Subsequent immunolabeling for CD4, CD43, and CD30 and clonal T-cell gene rearrangements enabled the correct diagnosis of cutaneous anaplastic large cell lymphoma. This case illustrates a pitfall in evaluating tumors in patients with known metastatic melanoma, and emphasizes the need for broad-spectrum immunohistochemistry in cases that are not clear-cut.

Extraneural ependymoma: distant bone, lung, liver, and lymph node metastases following bevacizumab.

Extraneural metastases of ependymoma are rare, and have been reported in the lungs, lymph nodes, pleura, mediastinum, liver, diaphragmatic muscle, and bone. We report a case of anaplastic ependymoma with distant metastases to the vertebral bones, lungs, liver, and lymph nodes following treatment with bevacizumab. Recent research has hypothesized that angiogenic tumors may develop means of resistance to antiangiogenic therapies, and some evidence suggests potential for antiangiogenic therapies to promote additional means for cancer spread. Nevertheless, antiangiogenic therapies continue to demonstrate potential as potent therapies for the treatment of many cancers, and should continue to be researched for future uses.

Urothelial carcinoma with prominent squamous differentiation in the setting of neurogenic bladder: role of human papillomavirus infection.

Squamous cell carcinomas of the urinary bladder are rare in the Western world; the majority of cases are reported in countries endemic to Schistosoma parasitic infections. Unlike squamous tumors of the uterine cervix or oropharynx, the human papillomavirus (HPV) is not commonly associated with bladder squamous cell carcinomas. We report on two cases of HPV-positive urothelial carcinomas of the urinary bladder with extensive squamous differentiation showing the typical basaloid, poorly differentiated morphology of HPV-associated tumors. These occurred in patients with neurogenic bladders who had long-standing histories of self-catheterization with tumors that tested positive for HPV by in situ hybridization. A retrospective review of our institutional database revealed four additional patients with bladder tumors showing squamous differentiation arising in the setting of neurogenic bladder. Review of these cases showed the more common well-differentiated keratinizing appearance of squamous cell carcinomas of the bladder. These tumors showed only patchy positivity for p16 immunohistochemical stain (not the diffuse strong staining seen in HPV-positive tumors), and the one tested case was negative for HPV by in situ hybridization. HPV infection and neurogenic bladder have been independently associated with increased risk of developing carcinoma in the urinary bladder; however, this is the first report of squamous tumors arising in the setting of concurrent neurogenic bladder and HPV infection. The morphology of these tumors is similar to that of other high-risk HPV-associated squamous carcinomas with a basaloid, poorly differentiated appearance and little to no keratin formation.

Atypical carcinoid metastasis to the skin.

Carcinoid tumors are derived from neuroendocrine cells, and are most frequently found in the gastrointestinal tract and bronchopulmonary system. Cutaneous involvement of carcinoid tumors is relatively rare, with isolated case reports in the literature. We detail a patient with stage IV pulmonary atypical carcinoid tumor with skin metastasis. This case is unusual because the patient did not have any erythema or induration of the scalp, only a complaint of pain. On biopsy, the tumor cells had cytologic features of a carcinoid tumor, but were arranged as infiltrating cords, small aggregates and single units, rather than the organoid or trabecular pattern seen in the primary tumor. Further, along with neuroendocrine markers, the tumor cells had the staining pattern of cytokeratin 7+/cytokeratin 20-/thyroid transcription factor-1+, supporting a carcinoid tumor of lung origin. Thus, this case of skin metastasis from an atypical pulmonary carcinoid tumor illustrates a unique clinical and histologic presentation.

Aberrant miR-182 expression promotes melanoma metastasis by repressing FOXO3 and microphthalmia-associated transcription factor.

The highly aggressive character of melanoma makes it an excellent model for probing the mechanisms underlying metastasis, which remains one of the most difficult challenges in treating cancer. We find that miR-182, member of a miRNA cluster in a chromosomal locus (7q31-34) frequently amplified in melanoma, is commonly up-regulated in human melanoma cell lines and tissue samples; this up-regulation correlates with gene copy number in a subset of melanoma cell lines. Moreover, miR-182 ectopic expression stimulates migration of melanoma cells in vitro and their metastatic potential in vivo, whereas miR-182 down-regulation impedes invasion and triggers apoptosis. We further show that miR-182 over-expression promotes migration and survival by directly repressing microphthalmia-associated transcription factor-M and FOXO3, whereas enhanced expression of either microphthalmia-associated transcription factor-M or FOXO3 blocks miR-182's proinvasive effects. In human tissues, expression of miR-182 increases with progression from primary to metastatic melanoma and inversely correlates with FOXO3 and microphthalmia-associated transcription factor levels. Our data provide a mechanism for invasion and survival in melanoma that could prove applicable to metastasis of other cancers and suggest that miRNA silencing may be a worthwhile therapeutic strategy.

MDM2 expression and regulation in prostate cancer racial disparity.

MDM2 is a key negative regulator of tumor suppressor p53. A single nucleotide polymorphism in the MDM2 promoter, SNP309, enhances transcriptional activation of MDM2 and has been associated with early onset of several types of cancer. In this study, we attempted to determine if the MDM2 SNP309 polymorphism plays a role in the aggressive phenotype seen in African American (AA) prostate cancer by examining the association between MDM2 SNP309 and MDM2 protein levels in prostate cancer (PCa) patients of different racial backgrounds. Prospectively enrolled PCa patients (AA=51, CA=50) were evaluated for MDM2 SNP309 and MDM2 protein expression. MDM2 overexpression, defined as >10% of tumor cells in three tissue cores, was assessed using immunohistochemistry on tissue microarray. MDM2 protein expression was significantly greater in CA than AA patients (78% versus 45% respectively, p=0.0007). Germline DNA was analyzed by PCR-RFLP then confirmed by DNA sequencing. MDM2 SNP309 genotype frequencies did not differ significantly between AA and CA PCa patients (AA: TT 68.6%, TG 25.5%, GG 5.9%; CA: TT 62.0%, TG 20.0%, GG 18.0%; p=0.16), suggesting that the MDM2 SNP309 allele does not play a significant role in the observed overexpression.