Folliculocentric squamous cell carcinoma with tricholemmal differentiation: a reappraisal of tricholemmal carcinoma.

BACKGROUND: The diagnostic criteria for tricholemmal carcinoma remain controversial, and even the existence of tricholemmal carcinoma has been the subject of debate. Follicular (infundibular) squamous cell carcinoma (SCC) is a distinctive subset of SCC, which develops solely with folliculocentricity, and displays the features of conventional SCC without tricholemmal differentiation. AIM: To examine the existence of pure folliculocentric SCCs showing tricholemmal differentiation, that is, tricholemmal carcinoma. METHODS: In total, 812 SCCs were examined, and those meeting the following diagnostic criteria were selected: (i) pure folliculocentricity without any associated Bowen's disease or actinic keratosis; (ii) composition primarily of lightly eosinophilic cells or clear cells containing glycogen; (iii) columnar lightly eosinophilic or clear cells aligned in a palisade along a discernible basement membrane; (iv) tricholemmal keratinization; (v) glycogen contained within the pale/clear cells; and (vi) cytological atypia and or infiltrative growth. We also evaluated whether the immunohistochemical profile [cytokeratin (CK)1, CK10, CK17, CD34 and D2-40] seen in normal hair follicles was retained in the selected lesions. RESULTS: Only two lesions met the criteria. The immunohistochemical profile of the normal outer root sheath cells was generally retained in these lesions, except for CD34. CONCLUSIONS: Tricholemmal carcinoma is a rare occurrence, but it does exist, and at least one type of tricholemmal carcinoma is considered to be related to follicular (infundibular) SCC.

Histiocytoid and signet-ring cell carcinoma of the axilla: a type of cutaneous apocrine carcinoma equivalent to histiocytoid lobular carcinoma of the breast?

There is a histopathological similarity between cutaneous apocrine carcinoma (CAC) and breast carcinoma. Cutaneous histiocytoid or signet-ring cell (SRC) carcinoma is a rare neoplasm, which usually occurs on the eyelid, and less commonly on the axilla. The precise histogenesis of this carcinoma remains controversial. We report the case of a man with a cutaneous histiocytoid SRC carcinoma of the axilla having histopathological and immunohistochemical features that were quite similar to histiocytoid lobular carcinoma (histiocytoid LC) of the breast, which is a subtype of classic invasive lobular carcinoma of the breast with apocrine differentiation. We consider this case to be a type of CAC equivalent to histiocytoid LC of the breast, based on the features and the occurrence on the axilla. The patient was treated with adjuvant chemotherapy according to the general guidelines for the treatment of breast carcinoma.

Nestin expression in stromal cells of trichoblastoma and basal cell carcinoma.

BACKGROUND: Both trichoblastoma and basal cell carcinoma (BCC) are considered to be a benign and malignant neoplasm of follicular germinative cells respectively. A recent investigation revealed that the mesenchymal cells in the perifollicular sheath and evolving follicular papilla of embryonic hair germs and those cells in hair follicles in early anagen express nestin. OBJECTIVE: The aim of the present study was to investigate whether trichoblastoma and BCC recapitulate the epithelial­mesenchymal interactions in embryonic hair germs or early anagen hair follicles by expressing nestin in stromal cells. METHODS: Immunohistochemical staining was performed with antibody against nestin for 15 trichoblastomas including large/small nodular, retiform and trichoepithelioma types, while adding the superficial type associated with nevus sebaceous and for 20 BCCs including superficial, nodular, nodulo-infiltrative, and infiltrative/micronodular types. RESULTS: In all 15 trichoblastomas, the stromal cells expressed nestin with variable positive reactions, except for superficial trichoblastomas within nevus sebaceous lesions, in which stromal cells were constantly positive for nestin. In all 20 BCCs, the stromal cells were basically negative for nestin. CONCLUSIONS: The development of trichoblastomas incompletely recapitulates the epithelial­mesenchymal interactions in embryonic hair germs or early anagen hair follicles, whereas BCCs fundamentally have lost this ability. Among the various types of trichoblastomas, the superficial type associated with nevus sebaceous was found to have the most similar character to either embryonic hair germs or early anagen hair follicles.

An organotypic culture system of Merkel cells using isolated epidermal sheets.

BACKGROUND: Merkel cells (MCs) exist in the epidermal basal layer, in contact with keratinocytes. This direct contact seems critical for maintaining MCs in vitro. OBJECTIVES: To estimate the effects of nerve cells on the maintenance of MCs within epidermal sheets in a new organotypic culture system of MCs. METHODS: We developed a new organotypic culture system of MCs, using MC-containing epidermal sheets embedded in collagen gel. To estimate the effects of nerve cells on the maintenance of MCs within the epidermal sheets, we cocultured nerve cells and MC-containing epidermal sheets. In these culture assemblies, cellular behaviour was analysed by histochemistry, immunohistochemistry, electron microscopy and enzyme-linked immunosorbent assay. RESULTS: This culture, even in the absence of neurotrophin (NT)-3 and nerve growth factor (NGF) (which are crucial for MC biology), retained cytokeratin (CK)-20-positive and neuroendocrine granule-containing MCs within the sheets for over 2 weeks. Coculture of MCs with PC-12 nerve cells significantly increased the number of MCs within the epidermal sheets, and the keratinocytes had almost identical expression levels of CK1, CK10, CK14 and the progenitor marker p63 to those produced by keratinocytes in vivo. Uptake of the growth marker bromodeoxyuridine by MCs and levels of NT-3 and NGF in the culture supernatants were undetectable in this system, regardless of the presence or absence of PC-12. CONCLUSIONS: The data suggest, first, that direct contact between MCs and keratinocytes may be critical for retaining MCs in vitro; second, that nerve cell-affected maintenance of keratinocyte differentiation, but not NT-3 and NGF, may contribute to MC maintenance; and third, that MCs are not able to grow, at least in our system. Our method would be useful for studying MC biology.

Fibrofolliculoma in a patient with tuberous sclerosis complex.

The occurrence of multiple fibrofolliculomas or trichodiscomas on the face and neck is clinically characteristic of Birt-Hogg-Dubé (BHD) syndrome, whereas the development of multiple fibrous papules or angiofibromas on the face is an important clinical sign of tuberous sclerosis complex (TSC). It has been suggested that a relationship exists between BHD syndrome and TSC and there was a case of BHD syndrome reported recently, in which multiple fibrous papules or angiofibroma lesions were observed. This report describes the first case, to our knowledge, of fibrofolliculoma in a patient with TSC.

Digital superficial angiomyxoma.

Superficial angiomyxoma is a rare, distinctive cutaneous soft-tissue neoplasm, which shows a prominent myxoid matrix with numerous blood vessels. This condition usually presents with a nodular lesion on the trunk, head and neck, or the genital region. We describe a case of superficial angiomyxoma, which presented at an unusual digital location while also demonstrating the features of transepidermal elimination, and which mimicked a digital myxoid cyst.

Changes in the number of Merkel cells with the hair cycle in hair discs on rat back skin.

BACKGROUND: Hair discs are known to contain a large number of Merkel cells and are ideal for investigating Merkel cell biology. Hair follicles, which are important elements of hair discs, undergo unique cyclical morphological and biological changes. OBJECTIVES: To define the relationships between the number and the morphology of Merkel cells within the hair disc in association with the hair cycle on rat back skin. METHODS: Merkel cells in hair discs were observed three-dimensionally using immunohistochemistry. Epidermal sheets were incubated with monoclonal murine antibody to CK20. As a result, Merkel cells in hair discs were clearly demonstrated as whole shapes and were counted under a light microscope. RESULTS: Merkel cells in hair discs increased during the early to middle phase of anagen and decreased during the middle phase of anagen to catagen and telogen in perinatal and postnatal rat back skin. We observed the morphological variation of Merkel cells in hair discs of rat back skin, and consequently divided them into two subtypes at the light microscopic level: the oval type and the dendritic type. The number of oval-type Merkel cells was not markedly affected by the hair cycle. In contrast, the number of dendritic-type Merkel cells markedly changed with the hair cycle. CONCLUSIONS: This difference of the hair cycle dependency between oval and dendritic-type Merkel cells suggests some functional differences, such as a secretory function, related to the hair cycle.

Childhood granulomatous periorificial dermatitis: lupus miliaris disseminatus faciei in children?

BACKGROUND: Childhood granulomatous periorificial dermatitis (CGPD) is a granulomatous disease characterized by monomorphous, small papular eruptions around the mouse, nose and eyes, and is thought to be closely related to perioral dermatitis. This condition has always been believed to occur more commonly in dark-skinned patients; however, recent observations have revealed CGPD to occur also in white patients. OBSERVATION: We report an 11-year-old Japanese boy with the characteristic features of CGPD. Although sarcoidosis and acne/granulomatous rosacea could be differentiated from CGPD, we could find no essential differences between CGPD and lupus miliaris disseminatus faciei (LMDF). The cases of LMDF in children, which were recorded in the Japanese literature, had highly similar clinicopathological features to those of CGPD. This case responded dramatically to topical tacrolimus in combination with the oral administration of minocycline. CONCLUSIONS: The entity 'facial idiopathic granulomas with regressive evolution' is considered to include LMDF (a common adult form), CGPD (a rare childhood form) and perioral dermatitis (a peculiar form exacerbated by topical corticosteroids). Topical tacrolimus may be recommended as one of the therapies for LMDF as well as CGPD.

Verrucous trichilemmal cyst containing human papillomavirus.

Verrucous cyst is an uncommon nonplantar epidermoid (infundibular) cyst with verrucous changes in its wall. We present the first case of trichilemmal cyst (isthmus-catagen cyst) with verrucous changes of its squamous lining.

The importance of serum creatine phosphokinase level in the early diagnosis and microbiological evaluation of necrotizing fasciitis.

BACKGROUND: Necrotizing fasciitis (NF) due to group A beta-haemolytic streptococci (GAS) is a rare but still life-threatening soft-tissue infection characterized by rapidly spreading necrosis of the muscle fascia and of the surrounding tissues. NF other than that due to GAS involves the participation of one or more anaerobes and/or of non-group A streptococci, Staphylococcus aureus, enteric organisms, and may be associated with a better outcome. Early diagnosis and treatment, consisting of surgical debridement along with appropriate antibiotic therapy, are required to reduce morbidity and mortality rates. OBJECTIVES: The aim of the study was to analyse the clinical and laboratory findings of patients with GAS NF and with non-GAS NF, and to identify which characteristics could help to diagnose NF in the early stages of infection. METHODS: We retrospectively analysed the clinical and laboratory findings of 43 cases of GAS and non-GAS NF that occurred in Belgium (n = 32) and at Saga Medical School (Japan) (n = 11) between May 1984 and December 2001. RESULTS: GAS NF more frequently occurred in previously healthy individuals than NF due to other pathogens (P < 0.05) but was associated with a poorer prognosis. Both for patients with GAS NF and with non-GAS NF, the first clinical manifestations often suggested a diagnosis of erysipelas or cellulitis and rarely evoked the correct diagnosis (12% and 15% of the cases, respectively). However, we found that creatine phosphokinase (CPK) values were far higher in patients with GAS NF than in those with non-GAS NF. CONCLUSIONS: Our data suggest that GAS may exert particular tropism and/or toxicity for muscle, responsible for early muscle necrosis. This indicates that elevated levels of CPK in a patient with erysipelas or cellulitis-like symptoms should clearly prompt the clinician to exclude the diagnosis of GAS NF.

The importance of serum creatine phosphokinase level in the early diagnosis, and as a prognostic factor, of Vibrio vulnificus infection.

BACKGROUND: Vibrio vulnificus infection causes rapidly progressive skin lesions and sepsis in compromised hosts with liver cirrhosis, and is often fatal. Early diagnosis and rapid treatment are important. OBJECTIVES: To clarify the characteristics of V. vulnificus infection that distinguish it from other cutaneous and soft-tissue bacterial infections and to confirm that serum creatine phosphokinase (CPK) levels are useful in early diagnosis, and are a prognostic factor for, V. vulnificus infection. METHODS: We analysed the clinical and laboratory findings (especially serum CPK levels) in eight patients with V. vulnificus infection who were treated at the Saga Medical School Hospital between January 1989 and December 1999. RESULTS: All eight patients had liver dysfunction and typical skin manifestations. Six had eaten raw seafood before onset. Seven patients had initial skin manifestations in their legs or feet and eventually died, despite prompt therapy in the intensive care unit. CPK levels of six of these seven patients were already elevated at their initial presentation. Only one patient, with skin manifestations solely on his left hand, showed and maintained a normal CPK level and survived. In 23 patients with cutaneous and soft-tissue infections (10 with necrotizing fasciitis, three with erysipelas, 10 with cellulitis), only three patients with necrotizing fasciitis and streptococcal toxic shock syndrome (STSS) showed CPK elevation. CONCLUSIONS: A high level of serum CPK in cutaneous or soft-tissue bacterial infection is considered useful for an early diagnosis of V. vulnificus infection and STSS. A history of eating raw seafood, underlying liver disease and multiple lesions suggest a diagnosis of V. vulnificus infection, rather than STSS.

Subcutaneous adipocytes promote the differentiation of squamous cell carcinoma cell line (DJM-1) in collagen gel matrix culture.

Cancer cell-stromal cell interaction plays a crucial role in the malignant growth of cancer cells. In the skin, the main stromal cell types consist of dermal fibroblasts and subcutaneous adipocytes. Fibroblasts are shown to promote the invasive growth of various cancer cell types. The interaction between cancer cells and stromal adipocytes, however, has not been sufficiently studied even in cutaneous carcinoma. To address the effects of adipocytes on the biologic behavior of cancer cells, we examined the growth and differentiation of a squamous cell carcinoma cell line of the skin (DJM-1), using a three-dimensional collagen gel matrix culture with a cutaneous environmental factor, air exposure. The growth was estimated by the uptake of bromodeoxy-uridine (BrdU) for 24 h. The BrdU indices of DJM-1 cells in stromal-cell-free, fibroblast-containing, and adipocyte- containing conditions were 19.7 +/- 1.9%, 19.8 +/- 2.8%, and 4.7 +/- 1.4%, respectively, whereas the BrdU index on the gel containing both fibroblasts and adipocytes was 10.4 +/- 3.3%. In terms of differentiation, DJM-1 cells cocultured with adipocytes constructed the best-organized stratified layer with a cornified-like structure in all conditions above. The differentiation markers involucrin and cytokeratin 10 were immunohistochemically detected in this structure of DJM-1 cells. Adipocyte-induced phenomena were not affected distinctively by air exposure. These results indicate that adipocytes, but not fibroblasts, promote the differentiation of squamous cell carcinoma cells (DJM-1) and inhibit their growth. These adipocyte-induced phenomena were not completely inhibited by fibroblasts. In conclusion, we suggest that stromal adipocytes may be involved in the differentiating mechanisms of cutaneous carcinoma cells.

Basal cell carcinoma in association with multiple trichoepitheliomas.

We report the case of a basal cell carcinoma (BCC) associated with multiple trichoepitheliomas (TEs) and include the results of histopathological and immunohistochemical studies. The patient had a large, pigmented nodule associated with 4 flesh-colored papules in the central facial area. Two of the 4 flesh-colored papules and the large pigmented nodule were excised. Histopathologically, the pigmented nodule was diagnosed as BCC and 2 of the papular lesions were diagnosed as TEs. In both the BCC and TEs, almost all of the basaloid aggregations were diffusely positive for cytokeratin (CK) 19, CK8 and CK8/18. Based on these clinicopathological observations and reports in the recent literature, these two neoplasms are considered to be highly related. BCC appears to differentiate toward follicular germinative cells, and TE is its benign counterpart.

Sebaceous carcinoma with apocrine differentiation.

A 54-year-old male had a dome-shaped and skin-colored nodule on his nose. Histopathologically, we diagnosed this neoplasm as a low-grade sebaceous carcinoma rather than a sebaceoma based on the scanning magnification and cytology. This low-grade sebaceous carcinoma was associated with glandular structures. We regarded the glandular structures as those of apocrine glandular differentiation based on 1) the histopathologic features of the glandular structures formed by columnar luminal cells with evidence of decapitation secretion; 2) the expression of cytokeratin (CK) 19, CK8, CK8/18, and CK7 in the luminal cells; 3) the positive reaction of carcinoembryonic antigen and epithelial membrane antigen on the luminal surface and in the cytoplasm of the luminal cells; and 4) the common embryologic origin of the folliculosebaceous-apocrine unit. We found CK15 expression in undifferentiated cells within the mantles of normal hair follicles, suggesting that sebaceous stem cells might exist in mantles as follicular stem cells exist in bulge areas. Pluripotent stem cells in the folliculosebaceous-apocrine unit can give rise to follicular stem cells, sebaceous stem cells, and apocrine stem cells. Our patient's neoplasm showed apocrine glandular differentiation and partial immunohistochemical positivity for CK15 in the neoplastic aggregations. We believe this neoplasm originated from pluripotent stem cells destined to become sebaceous stem cells or from sebaceous stem cells, which also have the ability to differentiate within apocrine glands.