Poromas with large lumens histopathologically mimicking syringocystadenoma papilliferum: Report of three cases.

We report on three patients exhibiting tumours with exophytic pedunculated structures with eroded surfaces. All cases showed the basic histopathological features of poroma accompanied by large, invaginated ductal structures lined by multiple layers of columnar or cuboidal cells. The columnar cells of invaginated ductal/cystic structures focally exhibited subtle features reminiscent of decapitation secretion along with dense infiltration of plasma cells in the surrounding stroma, mimicking syringocystadenoma papilliferum.

Standardization of terminology in dermoscopy/dermatoscopy: Results of the third consensus conference of the International Society of Dermoscopy.

BACKGROUND: Evolving dermoscopic terminology motivated us to initiate a new consensus. OBJECTIVE: We sought to establish a dictionary of standardized terms. METHODS: We reviewed the medical literature, conducted a survey, and convened a discussion among experts. RESULTS: Two competitive terminologies exist, a more metaphoric terminology that includes numerous terms and a descriptive terminology based on 5 basic terms. In a survey among members of the International Society of Dermoscopy (IDS) 23.5% (n = 201) participants preferentially use descriptive terminology, 20.1% (n = 172) use metaphoric terminology, and 484 (56.5%) use both. More participants who had been initially trained by metaphoric terminology prefer using descriptive terminology than vice versa (9.7% vs 2.6%, P < .001). Most new terms that were published since the last consensus conference in 2003 were unknown to the majority of the participants. There was uniform consensus that both terminologies are suitable, that metaphoric terms need definitions, that synonyms should be avoided, and that the creation of new metaphoric terms should be discouraged. The expert panel proposed a dictionary of standardized terms taking account of metaphoric and descriptive terms. LIMITATIONS: A consensus seeks a workable compromise but does not guarantee its implementation. CONCLUSION: The new consensus provides a revised framework of standardized terms to enhance the consistent use of dermoscopic terminology.

Platinum and anthracycline therapy for advanced cutaneous squamous cell carcinoma.

BACKGROUND: Because metastatic cutaneous squamous cell carcinoma (CSCC) is rare, standard chemotherapy has not been fully established. In Japan, combination platinum and anthracycline chemotherapy has been used for elderly patients with advanced CSCC because of its low toxicity. However, the clinical benefit of this therapy has not been fully examined. METHODS: We retrospectively examined the response rate of combination platinum and anthracycline chemotherapy for metastatic CSCC. RESULTS: Eight patients received combination chemotherapy for metastatic lesions; there were lymph node lesions in 6 patients and skin and lung lesions in one patient each. The combination regimens were as follows: cisplatin (CDDP) (60-90 mg/m(2)/day, day 1) and adriamycin (ADM) (20-40 mg/m(2)/day, day 1 or 2) was administered in 5 patients; CDDP (10-15 mg/m(2)/day, days 1-5) and epirubicin (epi-ADM) (10-15 mg/m(2)/day, days 1-5) was administered in 2 patients; and carboplatin (CBDCA) (200-400 mg/m(2)/day, day 1) and ADM (20-40 mg/m(2)/day, day 1 or 2) was administered in one patient. The responses were as follows: complete response in 2 patients (CDDP + ADM for lung metastasis, CDDP + epi-ADM for lymph node metastasis), partial response in 1 (CDDP + ADM for lymph node metastasis), stable disease in 2, and progressive disease in 3. A durable response was observed in 2 patients showing complete responses (58 and 112 months). CONCLUSIONS: The clinical effect of the combination of platinum and anthracycline for metastatic CSCC was limited despite the findings of two patients showing durable complete responses.

Hyperspectroscopic screening of melanoma on acral volar skin.

BACKGROUND/PURPOSE: Early detection and proper excision of the primary lesions of melanoma are crucial for reducing melanoma-related deaths. To support the early detection of melanoma, automated melanoma-screening systems have been extensively studied and developed. In this article, a previously reported hyperspectral imager and melanoma discrimination index are applied to the discrimination of acral lentiginous melanoma (ALM) from acral nevus (AN), and their diagnostic performance is reported. METHODS: The index expresses the disordered nature of each lesion including variegation in color based on variation in spectral information obtained from each lesion. Performance of the index has been studied in thirteen cases of ALM and seven cases of AN, obtained from patients and volunteers, all of whom were Japanese. RESULTS: The index discriminated ALM from AN with a sensitivity of 92% and a specificity of 86%. The area under the receiver operating characteristic curve was 0.97. CONCLUSION: The performance of the proposed objective melanoma discrimination index at a molecular pigmentary level approached that of clinical experts, using the three-step algorithm as the gold standard.

A case of systemic anaplastic large cell lymphoma with 'Hodgkin-like' appearance and skin involvement mimicking lymphomatoid papulosis.

We report a unique case of the CD30+ anaplastic large cell lymphoma (ALCL). A 44-year-old Japanese male presented with lymphadenopathy followed by skin involvement. Initially, a swollen cervical lymph node was recognized in 1989 and relapsed in 1991, which was histologically diagnosed as Hodgkin disease of nodular sclerotic type. In 1996, he presented ulcerative cutaneous nodules and swollen lymph nodes in his left inguinal region, which was then diagnosed with CD30+ ALCL. Both the lymphadenopathy and the skin lesion had been completely remitted by combining chemotherapy followed by radiotherapy. Thereafter, he had relapsing and remitting episodes of multiple papules and nodules on his face, trunk and extremities for 10 years. Repeated histopathological examination revealed similar tumor cell proliferation in the papules/nodules of the skin. Essentially similar immunohistochemical features, including CD30 and granzyme B expression, but not anaplastic lymphoma kinase (ALK), strongly suggested that all these tumors were sequential expression of one disease continued for 19 years. This case was finally diagnosed as CD30+ ALCL with unique skin involvement mimicking lymphomatoid papulosis (LyP).

Characteristic distribution of melanin columns in the cornified layer of acquired acral nevus: an important clue for histopathologic differentiation from early acral melanoma.

Clinical and histopathologic differentiation between early acral melanoma and acral nevus is often difficult. Dermoscopy is helpful in this differentiation. On dermoscopy, early acral melanoma shows the parallel ridge pattern showing band-like pigmentation on the ridges of the surface skin markings, whereas a representative dermoscopic pattern in acquired acral nevus is the parallel furrow pattern showing parallel linear pigmentation along the surface furrows. The parallel furrow pattern suggests that melanocytes of acral nevus preferentially proliferate in the crista profunda limitans, an epidermal rete ridge underlying the surface furrow. In the present study, however, we found that in 13 of 18 acquired acral nevi, proliferation of melanocytes were detected not only in the crista profunda limitans but also in the crista profunda intermedia (CPI), an epidermal rete ridge underlying the surface ridge. Very interestingly, Fontana-Masson staining of these acral nevi revealed that even when proliferation of melanocytes was prominent in the CPI, melanin granules in the cornified layer were observed as regular melanin columns situated under the surface furrows and were hardly detected under the surface ridges. These findings indicate that in acral nevus, melanin granules produced by melanocytes in the CPI are not transferred to the upper epidermis. Hence, we must be careful not to overdiagnose an acral melanocytic lesion in which an increased number of melanocytes are detected in the CPI. Even in such a case, if melanin granules in the cornified layer are detected as melanin columns regularly distributed under the surface furrows, the lesion is strongly suggested to be a benign acral nevus.

Stem cell spreading dynamics intrinsically differentiate acral melanomas from nevi.

Early differential diagnosis between malignant and benign tumors and their underlying intrinsic differences are the most critical issues for life-threatening cancers. To study whether human acral melanomas, deadly cancers that occur on non-hair-bearing skin, have distinct origins that underlie their invasive capability, we develop fate-tracing technologies of melanocyte stem cells in sweat glands (glandular McSCs) and in melanoma models in mice and compare the cellular dynamics with human melanoma. Herein, we report that glandular McSCs self-renew to expand their migratory progeny in response to genotoxic stress and trauma to generate invasive melanomas in mice that mimic human acral melanomas. The analysis of melanocytic lesions in human volar skin reveals that genetically unstable McSCs expand in sweat glands and in the surrounding epidermis in melanomas but not in nevi. The detection of such cell spreading dynamics provides an innovative method for an early differential diagnosis of acral melanomas from nevi.

Pathological activation of KIT in metastatic tumors of acral and mucosal melanomas.

Recent studies showed KIT gene aberrations in a substantial number of melanomas on acral skin and mucosa, suggesting the therapeutic benefit of tyrosine kinase inhibitors, such as imatinib. We therefore examined the expression and mutations of KIT in 4 primary and 24 metastatic acral and mucosal melanomas. Immunohistochemistry revealed moderate or strong KIT protein expression in 13 (48%) tumors. Sequence analysis revealed K642E and D820Y mutations in two metastases. Amplification of KIT was identified by real-time PCR in 4 tumors, including one that had K642E. Western blot analysis showed phosphorylation of the KIT receptor in 8 (62%) of 13 cryopreserved samples, indicating the frequent pathological activation of the receptor in vivo. Phosphorylation of KIT protein was detected in 2 tumors harboring KIT mutations, as well as in one tumor with KIT gene amplification. Furthermore, 5 tumors without detectable KIT gene aberrations showed phosphorylation of the KIT receptor. Expression of stem cell factor (SCF) in melanoma cells as well as stromal cells suggests SCF/KIT autocrine and paracrine activation in these tumors. Finally, we found significant growth suppressive effects of sunitinib in two acral melanoma cell lines; one harboring the D820Y mutation and one showing SCF-dependent KIT activation. These results show pathological activation of KIT in a substantial number of metastatic tumors of acral and mucosal melanomas, and suggest a potential therapeutic benefit of sunitinib for these melanomas.

Simultaneous suppression of MITF and BRAF V600E enhanced inhibition of melanoma cell proliferation.

Microphthalmia-associated transcription factor (MITF) is a master gene regulating differentiation of melanocytes, and a lineage survival oncogene mediating pro-proliferative function in malignant melanoma. However, high expression of MITF also has an anti-proliferative effect. To clarify the therapeutic implication of MITF as a molecular target for human melanoma, we evaluated the role of MITF in cell proliferation in a panel of human melanoma cell lines which express different levels of MITF. We found that both MITF depletion and forced expression of MITF significantly inhibited proliferation, suggesting that endogenous MITF is regulated at an appropriate level for melanoma cell proliferation, and could be a molecular target for melanoma. However, half of the melanoma cell lines in this study were relatively resistant to MITF depletion, indicating other treatment strategies are required for therapy. Our microarray analysis indicated that regulation of several cell growth-associated molecules may be independent of MITF and dependent on BRAF(V600E). Thus to enhance the anti-proliferative effect of MITF down-regulation, we combined shRNA-mediated MITF depletion with BRAF(V600E) inactivation, another known molecular target for melanoma. Indeed, simultaneous depletion of both MITF and BRAF(V600E) significantly inhibited melanoma growth even for the melanoma cell lines resistant to MITF depletion. These results suggest MITF may be an important molecular target for human melanoma and simultaneous inhibition of MITF and MAPK signaling may be an attractive strategy for melanoma treatment.

Transient myeloproliferative disorder with vesiculopustular eruption: Early smear is useful for quick diagnosis.

We report a male infant with Down syndrome who had a transient myeloproliferative disorder associated with skin lesions. He was transferred to a neonatal intensive care unit because of low body weight, fetal edema, disseminated intravascular coagulation, and 10% blast cells in the peripheral blood. On postnatal day (PD) 1, erythema with small papules, vesicles, and pustules appeared on the entire body. A smear preparation from the pustules on PD 2 showed 10% blast cells. A biopsy specimen taken on PD 5 revealed subcorneal pustules containing neutrophils and eosinophils. Genetic analyses detected a somatic mutation (197G>T, Glu295Stop) in exon 2 of GATA-1. On PD 10, the eruptions resolved spontaneously and the population of blast cells in peripheral blood decreased to 1%. The number of blast cells in pustules decreased markedly after three days. Therefore, we recommend that cytologic examination should be performed as early as possible.

Sentinel lymph node biopsy in Japan.

Similar to the practice in Western countries, intraoperative lymphatic mapping and selected lymphadenectomy (SLNB) have been validated and are widely performed for the staging of melanoma in Japan. Recent studies have shown that approximately 90% (73/81) of university hospitals and several cancer hospitals routinely perform SLNB, and half of all melanoma patients receive this examination. SLNB is performed according to a variation of the standard procedure described by Morton and Cochran. The most frequently used tracers are Tc(99m)-tin colloid or Tc(99m)-phytate for scintigraphy and patent blue violet or indigo carmine as a blue dye. Some institutions use indocyanine green, which is fluorescent and can be used to visualize sentinel lymph node(s) (SLNs) under an infrared camera. The recent detection rate of SLNs has increased to more than 95% with the method using blue dye, lymphoscintigraphy, and a handheld gamma probe. In a multicenter study, the rates of metastasis in SLN were as follows: pTis, 0% (0/36); pT1, 10.7% (6/56); pT2, 21.0% (13/63); pT3, 34.0% (35/103); and pT4, 62.4% (63/101). The metastasis rate was also significantly related to ulceration of the primary tumor. Here, we discuss data from Japanese patients and the present status of SLNB in Japan.