bromochloroacetic-acid and Keratosis--Seborrheic

A 79-year-old Japanese woman presented with an ulcerated, brown-red nodule in the center of a sharply demarcated, tan-brown plaque situated on the left side of her right breast. Histologically, the plaque demonstrated an acanthosis with an intraepidermal epithelioma of Borst-Jadassohn. Small oval nests of bland-appearing basophilic cells in the periphery gradually enlarged into nests of various sizes and irregular shapes, composed of densely cohesive, atypical basophilic cells above the central nodule. The atypical keratinocytes shifted to atypical spindle cells beneath the acanthotic epidermis, penetrating deep into the subcutaneous tissue. In addition to vimentin and p63, the spindle cells were positive for several cytokeratin (CK) markers, including AE1/AE3, 34βE12 and CK5/6, which showed more intense signals closer to the epidermis. Basophilic cells in the clonal nests were positive for p63, AE1/AE3, 34βE12 and CK5/6. The MIB-1 index was estimated at approximately 40-50% in both the bland-appearing and the atypical basophilic cells. We describe the first case of spindle cell squamous cell carcinoma arising in an intraepidermal epithelioma expressed by clonal Bowen's disease, which was difficult to differentiate from clonal seborrheic keratosis.

Topics: Aged; Biomarkers, Tumor; Bowen's Disease; Breast; Carcinoma, Squamous Cell; Dermoscopy; Diagnosis, Differential; Epidermal Cells; Epidermis; Female; Humans; Immunohistochemistry; Keratinocytes; Keratins; Keratosis, Seborrheic; Skin Neoplasms

Seborrheic keratoses (SKs) are harmless pigmented skin lesions (PSLs) that may be confused clinically not only with other benign conditions but also with cutaneous melanoma (CM). As SKs are one of the most common neoplasms in adults, the importance of their correct diagnosis is high. Misclassifying SK as malignant is not rare and leads to a high number of unnecessary biopsies. On the other hand, misdiagnosing CM as SK may have a large impact on prognosis or therapy.. In the non-invasive technique of dermatofluoroscopy, the fluorophores in melanocytes and keratinocytes are excited in vivo with nanosecond laser pulses and the resulting spectrally resolved, melanin-dominated fluorescence signals are used to differentiate between pigmented benign lesions and CM.. In this single-center, non-interventional study, 33 PSLs of 20 patients were scanned with dermatofluoroscopy in vivo. For all included cases, dermatofluoroscopic signals were compared to pathology classification.. The characteristic spectral features of SK were identified, where the signals are dominated by keratin, NAD(P)H, and melanin. The fluorescence spectra of SKs differed substantially from those of CM: a characteristic spectrum of SK has been identified in 27 of 28 SKs.. The high-accuracy differential diagnosis between CM and SK is possible with dermatofluoroscopy.

Topics: Adult; Diagnosis, Differential; Humans; Keratins; Keratosis, Seborrheic; Melanins; Melanoma; NAD; Skin Neoplasms

Seborrheic keratosis (SK) is classified into six types: hyperkeratotic; acanthotic; irritated; clonal; reticulated; and adenoid. However, the origins of the respective types of SK remain unclear.. To clarify the histogenetic origins of SK, we performed immunohistochemical studies of keratin (K) and filaggrin expression, taking into account the histopathological classifications of SK.. Hyperkeratotic SK mainly expressed K1, K10, and filaggrin. Acanthotic SK mainly expressed K14 with some K15. Irritated SK mainly expressed K14 and K17 in squamous eddies. Clonal SK, reticulated SK, and adenoid SK mainly expressed K14. The results show that hyperkeratotic SK differentiated towards squamoid terminal keratinization, whereas acanthotic, irritated, clonal, reticulated, and adenoid SK mainly differentiated towards basaloid undifferentiated cells. In addition, acanthotic SK differentiated towards the hair bulge, and irritated SK differentiated towards the follicular infrainfundibulum.. Based on the patterns of keratin and filaggrin expression demonstrated by the histopathological types, SK demonstrated diverse differentiation towards epidermal keratinization, basaloid cells, the infrainfundibulum and hair follicle bulges, which suggests that SK is in an undifferentiated and hyperproliferative state with heterogeneous differentiation. The immunohistochemical method of investigating patterns of keratin expression is useful in the differential diagnosis of cutaneous epithelial tumors.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers; Biopsy, Needle; Female; Filaggrin Proteins; Humans; Immunohistochemistry; Intermediate Filament Proteins; Keratins; Keratosis, Seborrheic; Male; Middle Aged; Sampling Studies; Sensitivity and Specificity

The histopathologic pattern of clonal seborrheic keratosis (SK) is quite similar to the nested pattern of pagetoid Bowen's disease [squamous cell carcinoma in situ (SCCIS)], and differentiation between the two can be challenging, especially when only small pieces are available for interpretation.. Eleven examples of clonal SK and 13 examples of pagetoid SCCIS were examined histopathologically (tabulating necrotic keratinocytes, suprabasal mitoses, infiltrate, parakeratosis housing plump nuclei, crowding of nuclei) and immunohistochemically (using Ki-67, bcl-2, cytokeratin 7 and cytokeratin 10). Sensitivity, specificity, p-values (Fisher's exact test, two-tailed) and positive/negative likelihood ratios (+LR/-LR) were calculated.. Significant differences were seen with regard to crowding (p = 0.0009) and mitoses (p = 0.0006); however, only complete absence of necrotic keratinocytes or of crowding appeared to be diagnostically convincing for a diagnosis of clonal SK (-LR < 0.01). Significant differences were also seen with bcl-2 (p = 0.0005) and cytokeratin 10 antibodies (p < 0.00001). Both markers displayed a typical nested pattern in clonal SK, nests being bcl-2-positive and cytokeratin 10-negative. Cytokeratin 10-negative nests were the most convincing criterion for differentiation between clonal SK and pagetoid SCCIS (+LR > 10, -LR < 0.01).. The most reliable marker to distinguish clonal SK from pagetoid SCCIS is cytokeratin 10 when it spares nests. Other criteria that assist in the differential diagnosis are bcl-2 expression, absence of crowding and of mitoses.

Topics: Biomarkers, Tumor; Bowen's Disease; Female; Gene Expression Regulation, Neoplastic; Humans; Keratinocytes; Keratins; Keratosis, Seborrheic; Male; Mitosis; Neoplasm Proteins; Skin Neoplasms

Seborrheic inclusion cyst (SIC) is a very rare variant of epidermal cyst of the skin. SIC shows seborrheic keratosis (SK)-like lesion in epidermal cyst. SIC is extremely rare; only 6 case reports have been published in the English literature. However, no immunohistochemical study of SIC has been reported. A 41-year-old Japanese man noticed a subcutaneous tumor in the neck. Physical examination showed slightly mobile tumor in the subcutaneous tissue, and total excision was performed. Grossly, the tumor (1 x 1 x 0.8 cm) was cyst containing atheromatous keratin. Microscopically, the lesion is a cyst containing keratins. About one half of the cyst showed features of epidermal cyst consisting of mature squamous epithelium with granular layers. The other one half showed SK-like epidermal proliferation. The SK-like area showed basaloid cell proliferation with pseudohorn cysts. No significant atypia was noted. Many eosinophilic cytoplasmic inclusion bodies were noted in the SK-like area. Immunohistochemically, the SK-like area was positive for pancytokeratin AE1/3, pancytokeratin CAM5.2, p63, and Ki-67 (labeling=8%) and HPV, but negative for p53. The pathological diagnosis was SIC.

Topics: Adult; Antigens, Viral; Biomarkers; Epidermal Cyst; Humans; Inclusion Bodies; Keratins; Keratosis, Seborrheic; Ki-67 Antigen; Male; Membrane Proteins; Papillomaviridae; Skin

Scale-crust, also termed "keratin crust", appears as yellowish-to-tan scale on the skin's surface. It is caused by hyperkeratosis and parakeratosis in inflamed areas of squamous cell carcinoma in situ (SCCIS, Bowen's disease) and is a critical dermoscopy feature for detecting this skin cancer. In contrast, scale appears as a white-to-ivory detaching layer of the skin, without crust, and is most commonly seen in benign lesions such as seborrheic keratoses (SK). Distinguishing scale-crust from ordinary scale in digital dermoscopy images holds promise for early SCCIS detection and differentiation from SK. Reported here are image analysis techniques that best characterize scale-crust in SCCIS and scale in SK, thereby allowing accurate separation of these two dermoscopic features. Classification using a logistic regression operating on color features extracted from these digital dermoscopy structures can reliably separate SCCIS from SK.

Topics: Area Under Curve; Carcinoma, Squamous Cell; Databases, Factual; Dermoscopy; Diagnosis, Differential; Humans; Image Processing, Computer-Assisted; Keratins; Keratosis, Seborrheic; Logistic Models; ROC Curve; Skin Neoplasms

The viral etiology of certain types of seborrheic keratosis (SK) has been a controversial subject in literature, with different molecular results. On the contrary, to the molecular approach, some have suggested that certain types of SK are indeed warts, due to their morphologic features. We decided to investigate the presence of coarse keratohyalin granules in cases of irritated SK.. We examined the last 60 cases with such a diagnosis in our Service of Anatomic Pathology and found these granules in eight cases (7.5%). The granules were evidenced in squamous eddies in four cases, while they were seen in foci of hypergranulosis from the top part of the epidermis in five cases. These granules were evidenced in a few foci in three cases while they were seen in multiple foci in five cases. In these eight cases, we also looked for other morphologic signs suggesting a viral origin, such as papilated, exo-endophytic configuration, parakeratosis at the tips of digitations, dilated vessels in the papillae and koilocytes. While six cases presented at least any of these other features, in two of the eight cases (25%), the only clue suggesting a viral origin was the evidence of the thick granules of keratohyalin.. We discuss the meaning of such a finding as described in literature, and conclude that it should be a specific feature to look out for, in cases of irritated SK, in order to exclude a diagnosis of verruca vulgaris.

Topics: Aged; Aged, 80 and over; Cytoplasmic Granules; Diagnosis, Differential; Epidermis; Female; Humans; Keratins; Keratosis, Seborrheic; Male; Middle Aged; Parakeratosis; Warts

Clear-cell acanthoma (CCA) has been reported to be a benign epidermal neoplasm; however, several authors have suggested alternative differentiation as well as other nosologic categories, including a reactive dermatosis. Fourteen CCAs, ten tricholemmomas, and seven cases of psoriasis were reviewed with conventional microscopy, periodic acid-Schiff stains, and immunohistochemical stains. Twelve of fourteen (86%) CCAs were associated with underlying or adjacent conditions. The CCAs stained immunohistochemically in a pattern similar to normal epidermis and psoriasis. Tricholemmomas stained in a distinctly different pattern with MNF116 and NGFR/p75. These cases demonstrate CCA in settings that reflect chronic inflammation, primarily scars and stasis dermatitis, and with an immunophenotype that parallels psoriasis. These findings support the contention that CCA does not show outer follicular sheath (tricholemmal) differentiation. Furthermore, these cases lend additional support to the contention that CCA represents a psoriasiform reaction pattern, which, in appropriately taken biopsies, usually has a demonstrable associated condition. Nonetheless, the precise nosology of this phenomenon has yet to be elucidated completely.

Topics: Acanthoma; Adult; Aged; Aged, 80 and over; Cicatrix; Dermatitis; Epidermis; Female; Hair Follicle; Hidradenitis Suppurativa; Humans; Hyperplasia; Keratins; Keratosis, Seborrheic; Male; Middle Aged; Molecular Weight; Neoplasms, Basal Cell; Nerve Tissue Proteins; Psoriasis; Receptors, Nerve Growth Factor; Skin; Skin Neoplasms

We observed seborrheic keratoses with many basilar clear cells, creating a microscopic pattern that mimicked a seborrheic keratosis involved by melanoma in situ.. We sought to report a series of these seborrheic keratoses and the immunohistochemical stains used to reach a proper diagnosis.. We reviewed 9 cases of seborrheic keratosis that had a distinctive pattern of basal clear cells with ample cytoplasm. All cases were evaluated by conventional microscopy, and Melan-A, S-100, and high molecular weight keratin 903 immunostains.. The basal clear cells failed to react with Melan-A and S-100 protein antisera. In contrast, these cells labeled with an antikeratin antibody in all cases. In all, 7/9 (78%) showed immunopositivity only at the peripheries of cells, creating a pattern that could be mistaken for a negative stain if not examined at high magnification.. This is a retrospective review of cases limited to a large referral dermatopathology service.. We describe a previously uncharacterized pattern of seborrheic keratosis that can microscopically mimic melanoma in situ. Careful conventional microscopy coupled with a panel of immunostains can allow the proper diagnosis to be reached.

Topics: Aged; Aged, 80 and over; Antibodies; Antigens, Neoplasm; Diagnosis, Differential; Female; Humans; Immune Sera; Immunoenzyme Techniques; Keratins; Keratosis, Seborrheic; Male; MART-1 Antigen; Melanoma; Middle Aged; Neoplasm Proteins; Retrospective Studies; S100 Proteins; Skin Neoplasms; Staining and Labeling

Verruciform xanthoma is xanthomatous dermal infiltrate in a proliferating epidermal lesion and is an uncommon phenomenon. It has been reported in various neoplastic or inflammatory conditions. We report a 72-year-old man who had an asymptomatic 1-cm black nodule on his abdomen. Histopathology showed a typical acanthotic type of seborrheic keratosis characterized by basaloid keratinocyte proliferation and pseudohorn cysts. Many aggregated xanthomatized cells were seen in dermal papillae within the acanthotic epithelium. Papillomatosis, parakeratosis, and neutrophil infiltrates, the histologic features of typical verruciform xanthoma, were not seen. The foamy cells were positive for CD-68 and vimentin and negative for cytokeratin and S-100. No human papillomavirus DNA was found by nested polymerase chain reaction. The blood lipid profile was normal. The presence of verruciform xanthomatous change in seborrheic keratosis provides further evidence that verruciform xanthoma may be a reactive phenomenon occurring in common skin disorders.

Topics: Aged; Antigens, CD; Antigens, Differentiation, Myelomonocytic; Humans; Immunohistochemistry; Keratins; Keratosis, Seborrheic; Male; Papillomaviridae; Polymerase Chain Reaction; S100 Proteins; Vimentin; Xanthomatosis

Recent genetic investigations support the idea that basal cell carcinoma (BCC) is trichoblastic carcinoma. However, it is generally thought that clear cell basal cell carcinoma is a result of degeneration rather than tricholemmal differentiation.. We report a case of BCC, with clear cell components, that developed within seborrheic keratosis, with histopathological and immunohistochemical findings.. The clear cell components in the present case showed the following four characteristics: (i) at the periphery of the aggregations, columnar clear cells were aligned in a palisade along a well-defined basement membrane; (ii) the nuclei of the columnar clear cells were at the pole opposite the basement membrane; (iii) the clear cells contained glycogen; (iv) in the aggregations with clear cell components, there was diffuse positive staining for cytokeratin 7 (CK7) (OV/TLR/30), but only the inner region stained positive for CK17. These four characteristics are comparable to those of the lower portion of normal outer root sheath. In addition, the BCC in the present case was partly composed of squamous cells that contained glycogen and were selectively positive for CK17 - features similar to those of squamous cells in normal outer root sheath.. Some clear cell BCCs are simply the result of degenerative change, but other clear cell BCCs may be the result of tricholemmal (at the lower portion) differentiation.

Topics: Biomarkers, Tumor; Carcinoma, Basal Cell; Cell Transformation, Neoplastic; Hair Diseases; Hair Follicle; Humans; Immunoenzyme Techniques; Keratin-7; Keratins; Keratosis, Seborrheic; Male; Middle Aged; Skin Neoplasms

Eleven cases of seborrheic keratoses with desmoplastic stroma and associated nests and cords of squamous epithelium simulating infiltrating carcinoma are presented. There were 7 males and 4 females ranging in age from 44 to 88 years (mean = 62). Eight cases were on the head and neck, one each on the lower and upper extremity, and one on the pubic area. Clinical diagnoses included seborrheic keratosis, squamous and basal cell carcinoma, and dermal nevus. Histologically, the lesions were characterized by exophytic growth pattern of basaloid and squamous cells, without cytologic atypia, and well-demarcated peripheral borders, typical for that seen in seborrheic keratoses. Squamous eddy formation with parakeratosis and spongiosis was present in all cases. Located within the body of the lesions were irregular nests and cords of squamous cells extending into the surrounding dermis with associated fibroblastic dermal proliferation trapping the epithelial nests, simulating invasive carcinoma. Immunohistochemically, the epithelial nests were cytokeratin positive and HPV negative, and the dermal stromal cells were vimentin positive and factor XIIIa, cytokeratin, and CD34 negative. Adjacent changes of carcinoma, trichilemmoma, verruca, or other adnexal neoplasm were not identified. Seborrheic keratoses may demonstrate desmoplastic changes analogous to that seen in desmoplastic trichilemmomas. Awareness of these changes in seborrheic keratosis will avoid misdiagnosis and excessive therapy.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers; Female; Humans; Immunoenzyme Techniques; Keratins; Keratosis, Seborrheic; Male; Middle Aged; Skin; Stromal Cells; Vimentin

The antibody 34-betaE12 stains selectively the keratins of basal cells. The aim of this study is to investigate the staining pattern of 34-betaE12 in borderline (keratoacanthomas and solar keratosis), and benign lesions (seborrheic keratoses). The proliferation index Ki-67 staining was also evaluated in these and also in malignant (basal and squamous cell carcinomas) cases. The staining pattern where the 34-betaE12 positive cells found in the basal, suprabasal epidermal layers was called "focal"; and the staining in all layers including upper spinous layer was called "diffuse". Mean proliferation index and the distribution pattern of Ki-67 immunohistochemical expression were assessed. Basal and suprabasal expression of 34-betaE12 significantly predominated in the normal parts of the epidermis, in eight out of 11 seborrheic keratoses (%73), one out of the 19 keratoacanthomas (%5), two out of 11 solar keratosis (18%). Statistical analysis revealed significant differences between mean level of Ki-67 expression of malignant (squamous cell carcinoma, basal cell carcinoma), benign (seborrheic keratoses) and premalignant (solar keratoses, keratoacanthomas) lesions (p<0.01). The distribution of staining pattern for Ki-67 paralleled to the staining pattern of 34-betaE12. Basal cell status assessment completed by 34-betaE12 may resolve some, but not all of the problems in terms of determining the presence of dysplasia.

Topics: Cell Division; Humans; Immunohistochemistry; Keratins; Keratoacanthoma; Keratosis; Keratosis, Seborrheic; Ki-67 Antigen; Precancerous Conditions; Skin

The frequency of amyloid deposits in cases of seborrheic keratosis was investigated In addition, the origin of amyloid protein(s) in lichen amyloidosis, macular amyloidosis and seborrheic keratosis was studied by immunohistochemical staining using a panel of anti-cytokeratin (CK) monoclonal antibodies. Amyloid deposits were found in 41 of 327 specimens (12.5%) from 301 cases of seborrheic keratosis. Amyloid deposits in seborrheic keratosis reacted with 6 of 12 CK antibodies and in lichen and macular amyloidosis (20 specimens) reacted with 5 of 12 CK antibodies. In seborrheic keratosis, antibody DE-K10 (labeling CK10) reacted with amyloid in 17 of 36 cases, antibody 34betaE12 (labeling CK1, 5, 10, 14) reacted in 33 of 39 cases, and antibody MNF116 (labeling CK5, 6, 8, 17) reacted in 32 of 35 cases. Among 20 specimens from lichen and macular amyloidosis, the three antibodies reacted with amyloid in the following rates: 1 with antibody DE-K10, all 20 with antibody 34betaE12, and 6 with antibody MNF116. These results suggest that amyloid deposits in seborrheic keratosis and lichen and macular amyloidosis may derive from epidermal cytokeratins.

Topics: Adult; Aged; Aged, 80 and over; Amyloidosis; Female; Humans; Immunohistochemistry; Keratins; Keratosis, Seborrheic; Male; Middle Aged; Skin

Seborrheic keratosis on the conjunctiva appears to have never been reported in the literature. The authors report here a well-documented case of seborrheic keratosis of conjunctiva clinically simulating a malignant melanoma.. Case report.. A 66-year-old man presented with a juxtalimbal pigmented tumor involving the temporal conjunctiva of his left eye. Because of the rapid enlargement of the mass within a period of 5 months, a clinical diagnosis of malignant melanoma was made. Cytopathologic examinations were performed by impression cytology before the patient underwent a wide en-block excision of the tumor.. Cytologic features were studied by impression cytology with periodic acid-Schiff-Papanicolaou stain. Immunochemical characteristics of tumor cells were studied by immunochemical stain of cytokeratin and HMB-45. Tumor morphology was observed by histopathologic examination.. Impression cytology disclosed basaloid cells intermixing with squamoid cells, and these cells demonstrated positive immunoreactivity to cytokeratin and no reactivity to HMB-45. Histopathologic examination of the tumor specimen established the diagnosis of seborrheic keratosis, and the results of immunohistochemical staining were consistent with those of the impression cytology with immunocytochemical staining.. The authors describe the first case report of conjunctival seborrheic keratosis and present its immunocytochemical and immunohistochemical characteristics. Such a benign lesion can clinically mimic a malignant melanoma.

Topics: Aged; Antigens, Neoplasm; Conjunctival Diseases; Conjunctival Neoplasms; Diagnosis, Differential; Humans; Immunoenzyme Techniques; Keratins; Keratosis, Seborrheic; Male; Melanoma; Melanoma-Specific Antigens; Neoplasm Proteins

The mode of differentiation of seborrhoeic keratoses was investigated by immunohistochemical staining using cytokeratin (CK) polypeptide-specific monoclonal antibodies and an antibody specific for the particulate form of epidermal transglutaminase (ETgase), and by applying an anti-human involucrin serum. The role played by (E)Tgase was further evaluated using an activity assay based on the covalent attachment of monodansylcadaverine. Samples of uninvolved epidermis served as reference tissue. CK reactivities suggested that seborrhoeic keratoses is a hyperproliferative disease with an epidermal CK composition. CK5 and CK14 were prominent markers of basal and basaloid keratinocytes, whereas a decrease in staining occurred in advanced maturation stages and areas of terminal keratinization. In contrast, CK1 and CK10 were prominent markers of suprabasaloid differentiation stages and produced complementary stainings to those of CK5 and 14. Generally, CK10 staining was more impressive than CK1 staining and seemed to start before CK1 staining. In contrast to CK10 staining, cornified areas lost CK1 reactivity. These staining patterns were similar to those observed in uninvolved reference tissues. The epidermal CK subset was further supplemented with the 'hyperproliferative' CK6 and 16 which occur sequentially. Positive staining for CK6 was noted from basal and proximal basaloid cells onwards, whereas distal basaloid cells additionally showed CK16 staining. The presence of other non-epidermal CK polypeptides could not be shown. The competence for other differentiation markers belonging to the group of (E)Tgase and cornifying cell membranes also evolved with a typical epidermal pattern. (E)Tgase activity was restricted to advanced and terminal stages of keratinization and was dual in nature, i.e. a diffuse cytoplasmic staining occurred together with a prominent staining of cornifying cell membranes.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Humans; Immunohistochemistry; Keratins; Keratosis, Seborrheic; Protein Precursors; Transglutaminases; Vimentin

The cytokeratin expression of seborrheic keratosis was studied by means of immunohistochemistry and compared with that of normal human skin. The following findings were obtained in seborrheic keratosis: (1) a partial lack of high molecular weight cytokeratin (#1/68 kD, #10/56.6 kD) in all ten cases examined; (2) the detection of cytokeratin typical for simple epithelia (#8/52.5 kD, #18/45 kD, #19/40 kD) in eight of ten cases; and (3) the detection of cytokeratin #5/58 kD in suprabasal cells in 5 of 10 cases. An immunoelectron-microscopic investigation, using an anti-keratin antibody against cytokeratin #19/40 kD, revealed a whirl-like arrangement of keratin filaments within immunoreactive cells, in contrast to a linear, parallel arrangement in non-immunoreactive cells. Cells known to express cytokeratin typical for simple epithelia, such as sweat gland cells or Merkel cells, were not observed. The altered cytokeratin gene-expression in seborrheic keratosis may be attributable to de-differentiation of tumor cells or potential re-differentiation towards embryonic keratinocytes.

Topics: Adult; Aged; Aged, 80 and over; Epithelium; Female; Humans; Immunohistochemistry; Keratins; Keratosis, Seborrheic; Male; Microscopy, Immunoelectron; Middle Aged; Skin