Satoru Aoyagi

Usefulness of real‐time tissue elastography for detecting lymph‐node metastases in squamous cell carcinoma

We report a case of invasive SCC arising from multiple lesions of Bowen’s disease with right inguinal lymph‐node metastasis. Assessment of superficial lymph‐node involvement by real‐time tissue elastography before surgery was found to be more useful than other noninvasive conventional methods. Histologically, the metastatic tumour cells were located asymmetrically in a small section of the cortical area of the right node, and this result was comparable with the elastographic findings. Additionally, we found that the presence of an asymmetrical cortical area with high elasticity should be included in the determination of metastatic involvement in small lymph nodes. It has high predictive values in the differentiation of benign and malignant superficial lymph nodes in patients with clinically node‐negative skin cancer. More cases are needed to validate this efficiency in differentiating benign from malignant lymph‐node status, but if confirmed, it may have an important role in the diagnosis of high‐risk cutaneous squamous cell carcinoma.

High expression of Ki-67 and cyclin D1 in invasive extramammary Paget's disease.

BACKGROUND Invasive extramammary Pagets disease (EMPD) is commonly associated with a poor prognosis. Although early detection of micro invasion can improve the prognosis, diagnosis is not always straightforward in some EMPD cases. Several clinical studies have proposed mechanisms underlying the increased invasiveness of EMPD; however, molecular markers indicative of the invasiveness have yet to be well characterized. OBJECTIVE The purpose of this study was to identify a reliable immunohistochemical marker for predicting the risk of invasion and metastasis in EMPD cases. METHODS A total of 32 specimens from 23 primary EMPD cases were analyzed by immunohistochemical staining. In formalin-fixed, paraffin-embedded tissue sections, immunolabeling of tumor cells were scored by stain intensity on a four-tiered scale. Using antibodies against several tumor proliferation markers, such as Her2, p53, Ki-67, cyclin D1 and Bcl-2, we determined the correlation between the expression of these molecular markers and the types of EMPD lesions (in situ, invasive or metastatic). RESULTS In contrast to Her2, p53 and Bcl-2, which are similarly expressed among different types of lesions, Ki-67 and cyclin D1 are expressed at significantly higher levels in invasive lesions than in situ lesions (P<0.01 and P<0.05, respectively). Furthermore, the mean of the sum of Ki-67 and cyclin D1 expression scores was significantly higher in invasive lesions, compared to the scores obtained for in situ lesions. In addition, the difference was more significant (P<or=0.001) than each of these independent marker. CONCLUSION Combined high expression of Ki-67 and cyclin D1 was highly associated with invasive lesions of EMPD.

c-MYC-Induced Sebaceous Gland Differentiation Is Controlled by an Androgen Receptor/p53 Axis

Summary Although the sebaceous gland (SG) plays an important role in skin function, the mechanisms regulating SG differentiation and carcinoma formation are poorly understood. We previously reported that c-MYC overexpression stimulates SG differentiation. We now demonstrate roles for the androgen receptor (AR) and p53. MYC-induced SG differentiation was reduced in mice lacking a functional AR. High levels of MYC triggered a p53-dependent DNA damage response, leading to accumulation of proliferative SG progenitors and inhibition of AR signaling. Conversely, testosterone treatment or p53 deletion activated AR signaling and restored MYC-induced differentiation. Poorly differentiated human sebaceous carcinomas exhibited high p53 and low AR expression. Thus, the consequences of overactivating MYC in the SG depend on whether AR or p53 is activated, as they form a regulatory axis controlling proliferation and differentiation.

Extensive proliferative nodules in a case of giant congenital naevus

The rare presence of proliferative nodules in cases of giant congenital naevus can, in some cases, be potentially misdiagnosed as neonatal melanoma. We report here a case of multiple, proliferative nodules found in a giant congenital naevus lesion in a female neonatal patient diagnosed with neurocutaneous melanosis. Our initial clinical observations of this case suggested the possibility of primary cutaneous neonatal melanoma or skin metastasis from a melanoma in the meninges or elsewhere in the central nervous system. However, histological examination revealed no sign of melanoma, abnormal mitosis, necrosis or any malignant change. Pagetoid arrays of naevus cells in the junctional zone and myxoid changes present in a significant portion of the dermis led to the diagnosis of proliferative nodules. Distinct histological patterns seen in the proliferative nodules in our neonatal patient were useful to differentiate between benign pigmented nodular lesions in a giant congenital naevus and malignant melanoma, and reduced the chance of misdiagnosis.

A novel splice site mutation in NCSTN underlies a Japanese family with hidradenitis suppurativa

Background  Hidradenitis suppurativa (HS) is a chronic follicular occlusive disease with characteristic recurrent draining sinuses, skin abscesses and disfiguring scars, mainly involving the axilla, groin, perianal and perineal regions. While most HS cases are nonfamilial, familial cases showing autosomal dominant inheritance have been reported. Recently, loss‐of‐function mutations in the genes encoding γ‐secretase have been identified as a cause of familial HS in the Chinese and British populations.

Lymphoma-type adult T-cell leukaemia-lymphoma with a bulky cutaneous tumour showing multiple human T-lymphotropic virus-1 DNA integration

Human T‐lymphotropic virus‐1 (HTLV‐1) is considered to be the cause of adult T‐cell leukaemia‐lymphoma (ATL). Monoclonal integration of HTLV‐1 proviral DNA, as is analysed by Southern blotting, has been demonstrated in ATL patients. Unusual integration patterns of HTLV‐1 proviral DNA have occasionally been described, and it is suggested that the patterns have clinical implications for ATL pathophysiology. Multiple, complete and defective types of integration patterns, in that order, are apparently associated with prognoses from good to poor. We report a 73‐year‐old Japanese woman with lymphoma‐type ATL and a bulky cutaneous tumour on the left thigh. Four bands of slightly differing intensity were seen after EcoRI digestion of skin and lymph node samples on Southern blot analysis of HTLV‐1 proviral DNA. Analysis for T‐cell receptor‐β gene revealed five novel bands after restriction enzyme digestion with HindIII, indicating that the patient has four separate tumour cell clones, each of which carries one copy of the provirus. She was treated with chemotherapy and radiation and remains under reasonable control despite some relapsing cutaneous nodules. The indolent course in this present case could be related to the multiple integration pattern of HTLV‐1 proviral DNA detected.

Eccrine porocarcinoma and eccrine poroma arising in a scar

SIR, Malignant tumours occurring at scar sites have long been reported in the literature. Most of them are squamous cell carcinomas and basal cell carcinomas. To our knowledge, eccrine porocarcinoma and eccrine poroma have not yet been described in association with scars. We report a case of eccrine porocarcinoma and eccrine poroma arising from a scar on the right foot. A 74-year-old woman had had paralysis of the lower half of the body for more than 50 years from spinal injury due to tuberculosis. She had scars caused by skin infections due to osteomyelitis and recurrent decubitus on the lower legs and feet. She presented with a partly ulcerated, fresh, red nodule surrounded by a brownish macule, 5 cm in diameter, situated within a scar on the anterior surface of her right foot (Fig. 1a). In addition, there was a slightly elevated, reddish but partly white nodule surrounded by a brown macule, 4 cm in diameter, situated in a scar on the posterior surface of her right foot (Fig. 1b). Histology of the nodule on the anterior surface of her right foot revealed a tumour composed of cords and broad columns of generally small basal-like cells extending into the dermis from the epidermis. The tumour cells were arranged irregularly and showed moderate atypia. The cells had large, hyperchromatic, irregularly shaped nuclei and some of them were multinucleated. Atypical mitotic figures were also seen. Ducts and small cysts were also seen within the tumour nests (Fig. 2a,b). The tumour cells stained positive with periodic acid–Schiff, alcian blue, epithelial membrane antigen, cytokeratin 7 (Fig. 2c) and carcinoembryonic antigen (Fig. 2d). However, diastase digestion, cytokeratin 20, S-100 protein and gross cystic disease fluid protein-15 were negative in the tumour cells. Based on these clinical and histopathological findings, the tumour on the anterior surface of the right foot was diagnosed as an eccrine porocarcinoma arising from a scar. Histopathologically, the nodule on the posterior surface of the right foot showed nests and islands of uniformly small basaloid cells, which were sharply demarcated from the adjacent keratinocytes. Broad, anastomosing cords and solid columns and nests of large cells extended into the dermis to varying levels. Duct-like structures were also found. The tumour was diagnosed as an eccrine poroma that occurred in association with a scar. Carcinomas are well known to arise frequently from a burn scar, and such carcinomas are termed Marjolin’s ulcers. Skin malignancies are thought to occur in association not only with burn scars, but also with scars in chronically inflamed or traumatized skin. Among such malignant tumours, squamous cell carcinomas occur most frequently in association Figure 1. (a) Anterior view of the right leg upon initial examination. Note a partly ulcerated, fresh, red nodule surrounded by a brownish macule (arrow). (b) On the posterior surface of the right foot there was a slightly elevated, reddish nodule surrounded by a brownish macule (arrow).

Response of intractable skin ulcers in recessive dystrophic epidermolysis bullosa patients to an allogeneic cultured dermal substitute.

Recessive dystrophic epidermolysis bullosa (RDEB) is an inherited skin disorder caused by mutations in the COL7A1 gene, which encodes collagen VII (COL7). Skin ulcers in RDEB patients are sometimes slow to heal. We describe here the therapeutic response of intractable skin ulcers in two patients with generalized RDEB to treatment with an allogeneic cultured dermal substitute (CDS). Skin ulcers in both patients epithelialized by 3-4 weeks after this treatment. Immunohistochemical studies demonstrated that the COL7 expression level remained reduced with respect to the control skin and that it did not differ significantly between graft-treated and untreated areas. Electron microscopy showed aberrant anchoring fibrils beneath the lamina densa of both specimens. In conclusion, CDS is a promising modality for treatment of intractable skin ulcers in patients with RDEB, even though it does not appear to increase COL7 expression.

Aggressive squamous cell carcinoma developing in a giant epidermal cyst of the abdomen

Mono-letter mnemonics in dermatology A mnemonic is a device or code that helps an individual to memorize key information about something. Many people are using mnemonics in teaching as they have been proven to be a successful learning aid. Recently, we have reviewed the use of mnemonics in dermatologic disorders. Many websites and books compile lists of mnemonics; thus, there may be more than one mnemonic for a given disorder. It is left to the individual to select one that he or she prefers. It is not uncommon for individuals to devise their own methods of remembering facts by constructing a word, song, picture, or incident. Self-made mnemonics are often particularly effective, as the time and creative energy devoted to their development result in increased recall. We wish to point out in this brief communication that using a word or phrase for mnemonics may at times become outdated, similar to a new edition of a book which replaces a previous one. Mnemonics, too, must accommodate new information so that students can reap the maximum benefit from this useful learning aid. Problems can arise when new information is added, because the addition of a letter to the existing word or phrase will ultimately change the composition of a mnemonic that has been in vogue for some time. For instance, the five painful tumors of the skin have been grouped nicely into the word “Bengal” (blue rubber bleb nevus, eccrine spiradenoma, neurilemmoma/neuroma, glomus tumor, angiolipoma/angioleiomyoma/angiosarcoma, and leiomyoma), or the phrase “blend an egg”, but now, with the potential addition of cutaneous endometriosis/calcinosis cutis and osteoma cutis, its use may be rendered obsolete. The new mnemonic for painful cutaneous nodules is BENGAL CO, where “CO” refers to the first letter of the last two tumors mentioned. In addition, a word or phrase that may be of interest to individuals in some countries, and easily recalled by them, might not be of interest elsewhere or may be difficult for persons in other places to recall. We wish to highlight that one good technique that can be used in framing mnemonics is a mono-letter. With this technique, it is possible to avoid the unnecessary inclusion of letters that change the meaning of the word, it can be used globally and internationally, and it is easily remembered because of its acceptability. This has been welcomed by other specialties. The letters may be employed in independent words or in words contained in a large statement. An example of the latter is the memorable description of Dowling–Degos disease by Wilson-Jones and Grice: demonstrating dusky dappled disfigurements and dark dot depressions, and disclosing digitate downgrowths delving dermally. Here, we list some of the “mono-letter” mnemonics that can be used as an aid in teaching dermatology: “a” in Addison’s disease [asthenia, areola pigmentation, arterial hypotension, alimentary abnormality (anorexia, symptoms of acute abdomen), anxiety, axillary and pubic hair thinning]; “d” and “m” in pellagra [dementia, diarrhea, dermatitis, death, meats (mostly fats), molasses, meal (corn)]; “l” in a dermatopathology pattern with superficial and deep perivascular infiltrates with lymphocytes predominant [ light eruption (polymorphus), lupus erythematosus, lymphocytic infiltrate of Jessner + deep figurate/gyrate erythema, Lyme disease, lues (syphilis) (+ plasma cells), lymphoma, leukemia, leprosy, indeterminate type (+ histiocytes)]; “p” in telogen effluvium (pregnancy, protein depletion, pills, propranolol, pyrexia, parturition, psychic stress); “p” in lichen planus (purple, polygonal, planar or flat, papules, pruritic, persistent, penile); “s” in superficial chronic glossitis [smoking, spirit (alcohol), spices, syphilis, sharp objects (trauma), sepsis (chronic debilitating diseases)].

Zosteriform and epidermotropic metastatic primary cutaneous squamous cell carcinoma

The first case of primary cutaneous squamous cell carcinoma (SCC) to cause zosteriform and epidermotropic metastasis to skin is reported. The patient is a 72-year-old Japanese woman. A cutaneous SCC appeared on the lateral side of her right knee and was removed. After dissection of the right inguinal lymph nodes, which revealed metastases, and irradiation of the right inguinal region, the patient presented with slightly pruritic and painful erythematous papules on the right hip and small brownish papules and vesicles with crusts on the anterior side of the right thigh. The eruptions were in a zosteriform distribution along the right L1 to L3 dermatomes. Histologically neoplastic squamous cell nests were observed in the epidermis, below the epidermal-dermal junction, and within lymphatic vessels in the deeper reticular dermis. We postulate that neoplastic cells with the ability to fuse with adjacent squamous epithelium may have been carried beneath the basal lamina or to the epidermis via dermal lymphatic backflow, resulting in epidermotropic metastasis.