Primary Dermal Melanoma

This is a lesion I am not familiar with. If I saw one with no overlying epidermal component and well separated from the overlying epidermis, I would think it was a metastasis! However this was excluded in these cases. The interesting thing is the thickness of the lesions but how accurate this is without overlying epidermal involvement I just dont know! The important message was the long survival time despite the thickness of the lesions.(IMCC)
Primary Dermal Melanoma
Distinct Immunohistochemical Findings and Clinical Outcome Compared With Nodular and Metastatic Melanoma

David S. Cassarino, MD, PhD; Erik S. Cabral, BS; Reena V. Kartha, PhD; Susan M. Swetter, MD


Arch Dermatol. 2008;144(1):49-56.

Objective To provide an updated and expanded analysis of clinical outcome and immunohistochemical (IHC) findings unique to primary dermal melanoma (PDM) that may be used to differentiate this entity from primary nodular melanoma (PNM) and cutaneous metastatic melanoma (MM).

Design Cohort analysis and extensive IHC panel comparing PDM with PNM and cutaneous MM.

Setting Melanoma clinics and pathology departments of academic and VA medical centers.

Patients Thirteen patients with a solitary dermal or subcutaneous nodule of histologically proven melanoma, prospectively followed through April 30, 2007.

Interventions Clinical, pathologic, and IHC assessment of patients diagnosed as having PDM.

Main Outcome Measures Long-term clinical outcome and determination of unique clinical and IHC features in the study cohort compared with other melanoma subtypes.

Results Histologically, there was no evidence of an overlying in situ component, ulceration, or regression, and there was no associated nevus in any cases. Clinical history and findings from workup, including imaging studies, skin examination, and sentinel lymph node biopsy, were negative for evidence of melanoma elsewhere. The mean Breslow depth was 9.6 mm. Two patients developed satellite or in-transit recurrences, 1 developed pulmonary metastasis, and another died of liver metastases. Overall, the cohort showed a 92% melanoma-specific survival rate at a mean duration of follow-up of 44 months. The IHC findings showed that PDM exhibited lower levels of staining for the antigens p53 (P = .02), Ki-67 (Mib-1) (P = .002), cyclin D1 (P = .001), and podoplanin (recognized by D2-40 antibody) lymphovascular staining (P <.001) compared with MM and PNM. All other markers were comparable.

Conclusions Patients with PDM have remarkably prolonged survival compared with patients with MM or PNM of similar thickness. Preliminary results suggest that PDM may be characterized by lower levels of p53, Ki-67, cyclin D1, and D2-40 compared with histologically similar MM and PNM.

Extramammary Paget's disease

Br J Dermatol. 2008 Feb;158(2):313-8.
Extramammary Paget's disease: treatment, prognostic factors and outcome in 76 patients.Hatta N, Yamada M, Hirano T, Fujimoto A, Morita R.Division of Dermatology, Toyama Prefectural Central Hospital, Nishinagae, Toyama 930-8550, Japan, and Department of Dermatology, Kanazawa University School of Medicine, Takara-machi, Kanazawa, Japan.

Background Extramammary Paget's disease (EMPD) is a rare cutaneous carcinoma usually presenting as a genital erythematous lesion in the elderly. Although most EMPD tumours are in situ, invasive EMPD has a poor prognosis. Objective To evaluate the clinical and pathological features of EMPD and determine prognostic factors for survival. Methods The medical records of 76 patients with EMPD were retrospectively reviewed. Results Of the 66 patients who underwent curative surgical excision, five (8%) developed local recurrence, but surgical margin ( 2 cm) was not correlated with local recurrence. Thirteen of the 76 patients (17%) developed systemic metastases and 10 of these died of disease. On univariate analysis, the presence of nodules in the primary tumour, clinical lymph node swelling, elevated serum carcinoembryonic antigen (CEA) levels, tumour invasion level and lymph node metastasis were significant prognostic factors. On multivariate analysis, invasion level and elevated serum CEA were the only factors that were significantly associated with reduced survival.

Conclusions Invasion level and lymph node metastasis are important prognostic factors in EMPD. In patients with in situ tumour, local tumour control is the major aim of treatment; however, wide surgical margins are not associated with a lower risk of local recurrence.

Polyoma virus and Merkel Cell Carcinoma

Researchers are unveiling a new virus in a report published online January 17 in Science. Dubbed the Merkel cell polyomavirus, it is the first to be strongly associated with a human tumor. Polyomaviruses have been shown to cause cancers in animals, but it is unclear what role, if any, they play in human cancer development. Although the important finding does not prove that the polyomavirus causes neuroendocrine cancer of the skin — also known as Merkel cell carcinoma — if confirmed, it might offer clues for future cancer treatment and prevention options.

Merkel cell carcinoma is a rare but extremely aggressive cancer that tends to spread rapidly. The incidence of this skin cancer has reportedly tripled over the past 20 years, to about 1500 cases a year. It tends to be seen in the elderly and in those with compromised immune systems, such as those with AIDS or patients taking transplant-related immunosuppressant drugs. About half of those with advanced Merkel cell carcinoma live 9 months or less.

"If these findings are confirmed, we can look at how this new virus contributes to a very bad cancer with high mortality and, just as important, use it as a model to understand how cancers occur and the cell pathways that are targeted," senior author Patrick Moore, MD, from the University of Pittsburgh School of Medicine, in Pennsylvania, said in a news release. "Information that we gain could possibly lead to a blood test or vaccine that improves disease management and aids in prevention."

Dr. Moore and his wife also discovered the cause of Kaposi's sarcoma. In 1993, the couple identified Kaposi's sarcoma–associated herpesvirus, the most common malignancy in AIDS patients and the most prevalent cancer in Africa.

During an interview with Medscape Oncology, Dr. Moore said his team was surprised by this latest finding. "We were certainly taken aback," he said. "I think anyone uncovering what could be a cause of cancer would be surprised by the finding," he laughed. A lot of work remains, but the Merkel cell polyomavirus might be an exciting clue.

Possible Cause of Rare Cancer Identified

Vaccines are now available against other causes of cancer, such as the human papillomavirus linked to cervical cancer. "The Merkel cell polyomavirus is another model that may increase our understanding of how cancers arise, with possibly important implications for nonviral cancers like prostate or breast cancer," coauthor Yuan Chang, MD, also from the University of Pittsburgh, pointed out in a news release.

Merkel cell polyomavirus, like the human papillomavirus, is said to integrate into the tumor cell genome, but not the genome of healthy cells. This integration destroys the virus's ability to replicate normally and might be the first step toward cancer.

Using a technique called digital transcriptome subtraction, the investigators looked at close to 400,000 messenger ribonucleic acid genetic sequences from 4 samples of Merkel cell carcinoma tumor tissue. They compared the sequences expressed by the tumor genome to gene sequences mapped by the Human Genome Project and systematically subtracted known human sequences to identify a group of genetic transcripts that might be from a foreign organism.

They found that 1 sequence was similar to, but distinct from, all known viruses. The team went on to show that this sequence belonged to a new polyomavirus present in 8 of 10 Merkel cell tumors they tested, but only 5 of 59 (8%) control tissues from various body sites and 4 of 25 (16%) control skin tissues.

"This is a rare cancer so it's hard to get enough tissue samples for large studies from just 1 center," Dr. Moore told Medscape Oncology. The group plans to continue collecting samples and will partner with others.

Even if the Merkel cell polyomavirus is proven to play a role in neuroendocrine cancer of the skin, Dr. Chang cautions that the virus is likely to be just part of a much larger picture.

Also Newly discovered virus, and strongly associated with Merkel cell carcinoma, is a member of the polyoma family. This cancer is most often found in immunocompromised persons, such as those afflicted by AIDS or taking organ transplant drugs which suppress the immune system.
According to the NY Times, this is the 7th virus linked to human cancers. (The others are Hep B & C with liver cancer, papilloma virus to cervical cancer, EBV with nose and pharynx cancer, and HTLV-1 to Human T cell leukemia.