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Background
During surgical procedures for a skin cancer, the pathologist is often called upon to evaluate the adequacy of the surgical margins, to ensure the surgeon has completely removed the tumor. A frozen section is performed by the pathologist where a small portion of the tissue is frozen, cut on a microtome, stained, and interpreted under the microscope by the pathologist. In this manner, the surgical margins can be completely cleared and the patient can be spared a second procedure.
Acrochordon (Skin Tag, Fibroepithelial polyp)
Actinic Cheilitis
Actinic Keratosis
Aggressive Digital Papillary Adenocarcinoma
Apocrine Tumors (Hidradenoma Papilliferum, Apocrine Cystadenoma)
Basal Cell Carcinoma
Basal Cell Carcinoma-Treatment and Prognosis
Birt-Hogg Dube Syndrome
Bowen's Disease
Chondroid Syringoma (Mixed Tumors)
Chronic Papillomatous Dermatitis
Cowden's Syndrome
Cylindroma of the Skin (Turban Tumors)
Cysts of the Skin
Eccrine Carcinoma (Porocarcinoma, Adenoid Cystic Carcinoma)
Epidermodysplasia verruciformis
Extramammary Paget Disease
Favre-Racouchot Disease (Nodular Elastosis with Cysts and Comedones)
Fibrous Papule (Angiofibroma of the skin)
Keratoacanthoma
Keratoses (Seborrheic Keratosis, Acanthomas)
Merkel Cell Carcinoma
Metastatic Tumors to the Skin
Microcystic Adnexal Carcinoma
Mixed Tumors (Chondroid Syringoma)
Myelomeningocele
Nevoid Basal Cell Carcinoma Syndrome (Gorlin Syndrome)
Nevus Sebaceus
Onychomatricoma
Pilomatricoma
Poroma (Eccrine Poroma)
Sebaceous Carcinoma (Sebaceoma, Sebaceous Adenoma, Sebaceous Epithelioma)
Soft Tissue Tumors (Neurofibroma, Granular Cell Tumor)
Spiradenoma (Eccrine Spiradenoma)
Squamous Cell Carcinoma
Squamous Cell Carcinoma-Treatment and Prognosis
Syringocystadenoma Papilliferum
Syringoma
Trichoblastoma
Trichodiscoma (Fibrofolliculoma)
Trichoepithelioma
Tricholemmal Tumors
Tumor of the Follicular Infundibulum
Verruca Vulgaris (Warts)One of the most puzzling questions is why don't more people get skin cancer? The familiar scenario is a fair skinned, fair haired, and blue eyed individual is at greater risk for skin cancer. Yet, even the majority of these individuals do not get skin cancer. Recently investigators at M.D. Anderson Cancer Center in Houston, TX, have discovered that the Fas ligand gene may provide a vital defense against basal cell and squamous cell carcinomas. This is discussed under Pathogenesis in the outline below.
Dermatologists also classify patients by skin types.
SKIN TYPE CHARACTERIZATION I Usually very fair, burns easily and severely and cannot tan II Usually fair, burns easily but minimally tans III Average White skin, burns slightly then tans light brown IV Generally darker, never burns, always tans rapidly V Never burns, tans brown VI Never burns, tans to black
OUTLINE
PATHOGENESIS CHARACTERIZATION APOPTOSIS Proliferation, apoptosis, and survivin expression in keratinocytic neoplasms and hyperplasias.
Bowen AR, Hanks AN, Murphy KJ, Florell SR, Grossman D.
Department of Dermatology, University of Utah, Salt Lake City, Utah, USA.
Am J Dermatopathol. 2004 Jun;26(3):177-81. Abstract quote
The dysregulation of apoptosis occurs in many cutaneous disease states. Several apoptosis inhibitors have been shown elevated in neoplasms and in some inflammatory conditions, but their relation to proliferative and apoptotic states has not been defined.
We examined the expression of the apoptosis inhibitor survivin in a panel of keratinocytic neoplasms and hyperproliferative skin lesions using both immunohistochemistry and a newly developed in situ hybridization technique. Proliferation and apoptotic indices were also assessed by immunohistochemical staining for proliferating cell nuclear antigen and TUNEL, respectively.
We found the highest rate of proliferation in verrucae and psoriasis followed by actinic keratosis, squamous and basal cell carcinoma, lichen simplex chronicus, and seborrheic keratosis; all were significantly (P < 0.05) higher than normal skin. Apoptotic rate was increased in squamous (P = 0.05) and basal cell carcinoma (P = 0.03), but not significantly different from normal skin in the other lesions tested. Survivin expression was seen in most neoplasms and hyperproliferative lesions, but not normal skin. Survivin expression was often restricted to the upper third of the epidermis in psoriasis and lichen simplex chronicus, whereas all the other lesions stained diffusely.
Survivin expression appears to be a consistent feature of keratinocytic neoplasms and hyperproliferative lesions and may contribute to the formation of epidermal hyperplasia seen in all of these disease states.CD95 (FAS LIGAND) Role of the Fas ligand and UVR Arch Dermatol 1997;133:1263-1270
The study was conducted in equal numbers of mice exposed to UV lamps. One group had the normal Fas ligand protein and the other group lacked it. Fourteen of the twenty mice lacking the protein developed genetic mutations after repeated UV exposure compared to only 1 of the 20 normal mice. The normal mice had three times the number of sunburned cells in their skin as compared to the Fas lacking mice.
What does this mean? The Fas ligand is a sentinel for cells exposed to UV irradiation. When these cells are present, Fas induces them to die by apoptosis, programmed cell death. This eliminates the damaged cells preventing further mutations which could lead to cancer. The next step is to investigate whether the same mechanism occurs in humans.What is it about UV radiation (UVR)? It is thought to lead to skin cancer by two mechanisms: mutation of cellular DNA and induction of a state of relative immunosupression. DNA absorbs UV light leading to production of an excited state in DNA, rearrangement of electrons, and finally production of a photoproduct. The products are usually dipyrimidine structures that lead to substitution of incorrect nucleic acids during replication, leading to mutations. UVB is definitely more mutagenic, commonly causing substitutions of thymine to cytosine. UVA is 1000x less likely to mutate the DNA, most commonly causing a thymine to guanine mutation. UVR also alters Langerhans antigen-presenting cell function and induces cytokines that promote suppressor immune pathway stimulation and inhibits helper pathways. UVR depletes Langerhans cells within the skin and stimulates keratinocytes to produce urocanic acid, tumor necrosis factor-alpha, and interleukin 10, which all lead to production of T-suppressor cells.
One may ask why the body evolved this elaborate mechanism. Some speculate that these immunosuppressive mechanisms exist to prevent any autoimmune reactions to new antigens fromed by the UVR exposure.COX-2 Immunohistochemical expression of cyclooxygenase-2 in skin cancers
Masayori Kagoura, etal.
Journal of Cutaneous Pathology 2001;28 (6): 298-302
Background: Cyclooxygenase (COX), also known as prostaglandin endoperoxide synthase, catalyses the conversion of arachidonic acid to prostanoids. There are two different isoforms of COX, referred to as COX-1 and COX-2. Overexpression of COX-2 has been demonstrated in various neoplasms, such as experimentally promoted tumors, gastrointestinal cancers and breast tumors.
Methods: In this study, we used immunohistochemistry to investigate COX-2 expression in a series of basal cell epitheliomas (BCE), Bowen’s disease, squamous cell carcinomas (SCC) and metastatic tumors of the skin.
Results: Four of 16 BCE showed a positive reaction for COX-2 and the adenoid type of BCE was the most strongly positive. In Bowen’s disease, the extent of positive staining for COX-2 was even higher than that in BCE. Eleven of 15 SCC showed a positive reaction for COX-2 and the pattern of staining was heterogeneous with more intense staining in the center of the tumor nests. In metastatic tumors, the percentage of COX-2-positive tumor cells and the intensity of their staining was low compared with Bowen’s disease and SCC.
Conclusions: These results indicate that the intensity of COX-2 staining and its heterogeneous distribution are related to the degree of cellular differentiation and the various phenotypes of tumor cells, but the extent of COX-2 staining did not correlate with the degree of malignancy.
DESMOGLEIN I Expression of desmoglein I and plakoglobin in skin carcinomas
HideyukiTada, MitsuoHatoko, AyaTanaka, MasamitsuKuwahara and TsutomuMuramatsu
J Cutan Pathol 2000;27 (1), 24-29 Abstract quote
Reduction or absence of cell-cell adhesion molecules has been reported in various carinomas and the abnormal expression of these molecules contributes to the invasive and metastatic behavior of malignant tumor cells. In epidermal keratinocytes, the main cell-cell adhesion systems are adherens junctions and desmosomes. Previous studies have shown that, in skin carcinomas, the decreased expression of E-cadherin, major constitutional glycoprotein of adherens junctions, is associated with the invasive and metastatic ability of the tumor cells.
In the present study, we examined the expression of desmoglein I and plakoglobin, the constitutional components of desmosomes, in various skin carcinomas such as basal cell carcinoma (BCC), squamous cell carcinoma (SCC), extramammary Paget's disease and Bowen's disease by an immunofluorescence method.
In normal human skin, desmoglein I and plakoglobin were strongly expressed in the intercellular space of the epidermis except for the basal cell layer. In BCC and SCC, the expression of desmoglein I and plakoglobin was markedly reduced or absent in tumor cells. In carcinoma in situ of Paget's disease, compared with the normal epidermal cells surrounding tumor cell nests, the expression of these molecules was reduced in tumor cells. In Paget's disease with dermal infiltration of tumor cells, the expression of these molecules was almost absent throughout the epidermis. In Bowen's disease, the expression of desmoglein I was reduced in the clumping cells and dyskeratotic cells.
These results suggest that the expression of desmosomal cadherin is reduced or absent in human skin carcinomas, and that reduction of these molecules may also contribute to the invasiveness and metastasis of skin carcinomas.
E-CADHERIN
E-cadherin promoter hypermethylation in preneoplastic and neoplastic skin lesions.
Chiles MC, Ai L, Zuo C, Fan CY, Smoller BR.
Department of Pathology, University of Arkansas for Medical Sciences, Little Rock, Arkansas 72205, USA.
Mod Pathol. 2003 Oct;16(10):1014-8 Abstract quote.
E-cadherin is a calcium-dependent, intercellular adhesion molecule that is specifically expressed in epithelial tissues and plays an important role in maintaining epithelial stability. E-cadherin is widely regarded as a prognostic marker in many types of human cancers. The inactivation of the E-cadherin gene is linked to increased potential for tumor invasiveness and distant metastasis.We previously demonstrated reduced expression of E-cadherin protein immunohistochemically in invasive squamous cell carcinomas of the skin as compared with adjacent normal skin. An epigenetic alteration in association with promoter hypermethylation is one important mechanism of gene silencing. In the present study, we analyze the E-cadherin gene promoter hypermethylation in preneoplastic and neoplastic skin lesions to determine whether epigenetic alteration of the E-cadherin gene also plays an important role in cutaneous squamous carcinogenesis. A total of 33 cases was examined for evidence of E-cadherin promoter hypermethylation, and these consist of nine cases of spongiotic dermatitis as nonneoplastic skin control, nine cases of actinic keratosis, eight cases of squamous cell carcinoma in situ, and seven cases of invasive squamous cell carcinoma. Promoter hypermethylation of the E-cadherin gene was detected in 6 of 7 cases (85%) of invasive squamous cell carcinoma, 4 of 8 cases (50%) of squamous cell carcinoma in situ, 4 of 9 cases (44%) of actinic keratosis, and 2 of 9 cases (22%) of nonneoplastic skin.
We conclude that E-cadherin promoter hypermethylation occurs frequently and may represent an important mechanism of E-cadherin inactivation in cutaneous preneoplastic and neoplastic lesions. The frequencies of E-cadherin promoter hypermethylation appear to be correlated with more advanced stage of squamous carcinogenesis in skin.
Ets-1
Ets-1 immunohistochemical expression in non-melanoma skin carcinoma.
Keehn CA, Smoller BR, Morgan MB.
Department of Pathology, University of South Florida College of Medicine, Tampa, FL, Department of Pathology, University of Arkansas for the Medical Sciences, Little Rock, Arkansas, The James A. Haley Veterans Hospital, Tampa, FL, and Bay Area Dermatopathology Ameripath Tampa, FL, USA.
J Cutan Pathol. 2004 Jan;31(1):8-13 Abstract quote.
BACKGROUND: Ets-1 oncoprotein is a transcription factor known to regulate the expression of numerous genes important in extracellular matrix remodeling and angiogenesis. Up-regulation of Ets-1 has been shown to be important in a variety of human malignancies and to correlate with prognosis. To our knowledge, this oncoprotein has not been examined in non-melanoma skin carcinomas.
DESIGN: A series of 26 primary cutaneous skin lesions with patient records were independently examined for diagnosis confirmation and immunohistochemical expression by two dermatopathologists. The immunohistochemical expression for Ets-1 (Novocastra, Newcastle Upon Tyne, England, UK) was scored by an average of the mean labeling intensity (MLI), where no nuclear staining = 0, weak nuclear staining = 1, moderate nuclear staining = 2, and strong nuclear staining = 3.
RESULTS: All basal cell carcinoma (BCC) and Merkel cell carcinoma (MCC) cases exhibited negative nuclear staining, for an average MLI of 0. Keratoacanthomas, squamous cell carcinoma in situ (SIS), and well-differentiated squamous cell carcinomas (SCCs) exhibited negative to weak nuclear staining, for an average MLI of 0.4 +/- 0.3. Moderately differentiated SCCs exhibited moderate nuclear staining, for an average MLI of 1.8 +/- 0.6. Poorly differentiated SCCs and metastatic SCCs exhibited very strong nuclear staining, with an average MLI of 2.8 +/- 0.2.
CONCLUSIONS: Ets-1 is not expressed in cutaneous BCC or MCC and is weakly expressed in SIS and forms of well-differentiated SCC. Although the intensity of Ets-1 immunostaining distinguished between well-differentiated and poorly differentiated SCC (p < 0.0001), it failed to discriminate between in situ and well-differentiated SCCs. The preliminary data suggests Ets-1 may be important in the pathogenesis of invasive SCC.INSULIN-LIKE GROWTH FACTOR-1 RECEPTOR
Expression of insulin-like growth factor-I receptor in primary cutaneous carcinomas.
Keehn CA, Saeed S, Bickle K, Khalil FK, Morgan MB.
Department of Pathology, University of South Florida College of Medicine, Tamp, FL, USA.
J Cutan Pathol. 2004 May;31(5):368-72. Abstract quote
Background: Insulin-like growth factor-I (IGF-I) is the principal mediator of growth hormone, exerting its effects through binding of the insulin-like growth factor-I receptor (IGF-IR). Post-receptor activation leads to the production of transcription factors involved in cell proliferation, differentiation, transformation, and survival. Data indicate that IGF-IR is involved in tumorigenesis. To our knowledge, this receptor has not been previously studied in primary cutaneous carcinomas.
Methods: Twenty-five cases of primary cutaneous carcinomas consisting of three keratoacanthoma-type squamous cell carcinomas (KAs), two squamous cell carcinomas in situ (SCCs in situ), eight squamous cell carcinomas (SCCs), three conventional basal cell carcinomas (BCCs), two morpheaform basal cell carcinomas (M-BCCs), and seven Merkel cell carcinomas (MCCs) were analyzed for IGF-IR immunohistochemical expression using IGF-IR mouse monoclonal antibody (dilution 1 : 50) using the avidin-biotin-peroxidase complex method.
Results: Normal epidermis was negative for IGF-IR expression. Normal eccrine glands and outer root sheath strongly expressed IGF-IR. All KAs, SCCs in situ, SCCs, and BCCs were negative for IGF-IR expression. Six of seven (86%) of the MCCs stained with IGF-IR strongly, showing cell membrane accentuation and a perinuclear dot-like pattern.
Conclusion: The data suggest that IGF-IR immunopositivity in MCCs might constitute a diagnostic tool in discriminating between SCCs and BCCs. Although the possible pathogenic significance of the perinuclear dot-like staining pattern observed in these neoplasms is unknown, its pattern is similar to what has been previously described with cytokeratin-20 immunostaining.MAGE-A4 (CANCER TESTIS ANTIGEN)
Department of Dermatology, University Hospital Zurich, Zurich, Switzerland.
Background: Lifetime risk for squamous cell carcinoma (SCC) of the skin is 1:30. Risk in organ-transplant recipients (OTR) is increased over 60-fold through long-term drug-induced immunosuppression. MAGE family-derived peptides are cancer/testis antigens recognized by specific CD8(+) T cells and employed for immunotherapy. We were interested in the frequency and distribution of MAGE-A4 in epithelial skin tumors of OTR and immunocompetent patients.
Methods: mAb 57B predominantly recognizing MAGE-A4 was used to stain 119 formalin-fixed, paraffin-embedded epithelial skin tumors (actinic keratosis, bowenoid actinic keratosis, Bowen's disease, and SCC; n = 17, 25, 61, 16, respectively) in immunocompetent patients (n = 84) and OTR (n = 35).
Results: All four epithelial skin tumors showed comparable immunoreactivity ranging from (25-71%, p = 0.361). Scattered immunoexpression pattern was more frequent in OTR (p = 0.025). SCC showed polarized immunoreactivity basally (p = 0.002).
Conclusion: MAGE-A4 was expressed in a large part of epithelial skin tumors with predominantly scattered immunoexpression pattern in OTR. The difference in immunoexpression pattern for immune status was limited, suggesting important non-immunosuppressor-mediated mechanisms for increased skin carcinogenesis in OTR. mAb 57B may be a helpful tool for immunohistochemistry and micrographic surgery using formalin-fixed paraffin-embedded tissue.MICROSATELLITE INSTABILITY
Microsatellite instability and its relevance to cutaneous tumorigenesis.Hussein MR, Wood GS.
The Department of Medicine (Dermatology), University of Wisconsin and William S. Middleton Memorial Veteran Hospital, Madison, WI, USA.
J Cutan Pathol 2002 May;29(5):257-67 Abstract quote Increasing evidence suggests that human tumors sequentially accumulate multiple mutations that cannot be explained by the low rates of spontaneous mutations in normal cells (2-3 mutations/cell).
The mathematical models estimate that for the solid tumors to develop, as many as 6-12 mutations are required in each tumor cell. Therefore, to account for such high mutation rates, it is proposed that tumor cells are genetically unstable, i.e. they have genome-wide mutations at short repetitive DNA sequences called microsatellites. Microsatellite repeats are scattered throughout the human genome, primarily in the non-coding regions, and can give rise to variants with increased or reduced lengths, i.e. microsatellite instability (MSI). This instability has been reported in an increasing number of cutaneous tumors including: melanocytic tumors, basal cell carcinomas and primary cutaneous T-cell lymphomas. Moreover, MSI has been observed in skin tumors arising in the context of some hereditary disorders such as Muir-Torre syndrome, Von Recklinghausen's disease and disseminated superficial porokeratosis. While MSI in some of these disorders reflects underlying DNA replication errors, the mechanism of instability in others is still unknown.
Thus far, MSI is considered to be a distinct tumorigenic pathway that reveals surprising versatility. The ramifications for cutaneous neoplasms warrant further investigation.
NITRIC OXIDE SYNTHASE Immunohistochemical study of inducible nitric oxide synthase in skin cancers
Masayori Kagoura, Chihiro Matsui, Masahiko Toyoda and Masaaki Morohashi
Department of Dermatology, Faculty of Medicine, Toyama Medical and Pharmaceutical University, Toyama, Japan
Journal of Cutaneous Pathology 2001;28 (9), 476-481 Abstract quote
Background: Nitric oxide (NO) is synthesized from the amino acid L-arginine by NO synthase (NOS). Experimental evidence suggests that increased express of inducible NOS (iNOS), which is an NOS isoform and calcium independent, is related to various pathological processes, such as inflammation and cancer.
Methods: In this study, we used immunohistochemistry to investigate iNOS expression in a series of basal cell carcinomas (BCC), Bowen’s disease, squamous cell carcinomas (SCC), extramammary Paget’s disease (EPD) and metastatic tumors of the skin.
Results: Only 1 of 16 BCC cases was positive for iNOS and the intensity of staining was weak. In most of the 10 cases of Bowen’s disease, iNOS was weakly expressed and there was a wide range in the percentage of positive tumor cells. Twelve of the 16 cases of SCC were positive for iNOS and the extent of positivity was greater than in Bowen’s disease. Two of the 7 cases of EPD were positive for iNOS, and 12 of the 15 cases of metastatic cancer were positive. Well-differentiated adenocarcinomas were diffusely positive, whereas poorly-differentiated ones showed strong and heterogeneous staining.
Conclusions: These results indicated that the expression of iNOS may reflect the proliferation of tumor cells and that a heterogeneous distribution of iNOS may correlate with a wide variety of biological behavior of tumor cells.
NUCLEOLAR ORGANIZER REGIONS
- Nucleolar organizer region staining patterns in paraffin-embedded tissue cells from human skin cancers.
Romao-Correa RF, Maria DA, Soma M, Sotto MN, Sanches JA Jr, Neto CF, Ruiz IR.
Genetics Laboratory, Butantan Institute, Sao Paulo, SP, Brazil.
J Cutan Pathol. 2005 May;32(5):323-8. Abstract quote
Background: Increased number of nucleoli (nucleolar organizer regions, NORs) with abnormal shapes and sizes, including small dots, has been used as prognostic tools to evaluate tumor proliferation levels and troublesome borderline lesions. In this study, NOR patterns of skin cancers were performed in the search of a valuable prognostic method to complement other histological procedures.
Methods: Paraffin-embedded tumor tissue was obtained from basal and squamous cell carcinomas, cutaneous malignant melanoma, premalignant lesions, and Skmel-28 human melanoma cells. Slices were dewaxed and AgNOR stained. The patterns were scored and submitted for statistical analyses.
Results: All types of cancer cells showed variable numbers of abnormally shaped nucleoli and dot-like structures. Only tumor cells presented four or more nucleoli, with or without dots, while 85% of the normal cells had one single NOR without dots. Most data were statistically significant when compared to normal cells. As a whole, squamous cell carcinoma and malignant melanoma tumor cells had less NOR alterations than basal cell carcinoma (BCC) tumor types.
Conclusions: Changes in the number and shape of nucleoli present in malignant cells could be attributed to increased levels on rDNA transcription on cancer cells, besides abnormal remodeling of chromatin, which could disrupt proper nucleoli association. Increased genetic alterations on malignant basal cells could contribute to impair invasive and migration abilities of BCC tumors.RETINOBLASTOMA GENE
Retinoblastoma gene expression in human non-melanoma skin cancer.
Edwards MJ, Thomas RC, Wong YL.
University of Wales Institute, School of Applied Sciences, Llandaf Campus; and Department of Dermatology, University of Wales College of Medicine, Heath Park, Cardiff, UK
J Cutan Pathol. 2003 Sep;30(8):479-85. Abstract quote
BACKGROUND: The aberrant expression of both the retinoblastoma and p53 tumor suppressor genes has been associated with more aggressive tumors, metastasis and lower survival.
METHODS: We have evaluated immunohistochemically the expression of pRB in a panel of non-melanoma skin cancers containing p53 somatic mutations.
RESULTS: Nuclear anti-p53 staining was detected in 18 (72%) differentiated squamous cell carcinomas, six (100%) undifferentiated squamous cell carcinomas and seven (28%) basal cell carcinomas. A correlation was observed between p53 expression and the proliferative activity of differentiated squamous cell carcinomas (P < 0.066), undifferentiated squamous cell carcinomas (P < 0.05) and basal cell carcinomas (P < 0.01). Tumors were selected for mutant p53 expression by PCR-directed DNA sequencing and pRB expression measured immunohistochemically. Anti-pRB reactivity was detected in the nuclei of basal and suprabasal layer cells of normal epidermis, and in the proliferative compartment of all the differentiated squamous cell carcinomas, and basal cell carcinomas. A correlation was observed between pRB expression and the proliferative activity of the differentiated squamous cell carcinomas (P < 0.01) and basal cell carcinomas (P < 0.025). However, anti-pRB reactivity was not detected in the six anti-p53 reactive undifferentiated squamous cell carcinomas.ULTRAVIOLET RADIATION
- Ultraviolet radiation and skin cancer: molecular mechanisms.
Hussein MR.
Pathology department, Assuit University Hospitals, Assuit University, Assuit, Egypt.
J Cutan Pathol. 2005 Mar;32(3):191-205. Abstract quote
Every living organism on the surface of the earth is exposed to the ultraviolet (UV) fraction of the sunlight. This electromagnetic energy has both life-giving and life-endangering effects. UV radiation can damage DNA and thus mutagenize several genes involved in the development of the skin cancer. The presence of typical signature of UV-induced mutations on these genes indicates that the ultraviolet-B part of sunlight is responsible for the evolution of cutaneous carcinogenesis.
During this process, variable alterations of the oncogenic, tumor-suppressive, and cell-cycle control signaling pathways occur. These pathways include (a) mutated PTCH (in the mitogenic Sonic Hedgehog pathway) and mutated p53 tumor-suppressor gene in basal cell carcinomas, (b) an activated mitogenic ras pathway and mutated p53 in squamous cell carcinomas, and (c) an activated ras pathway, inactive p16, and p53 tumor suppressors in melanomas.
This review presents background information about the skin optics, UV radiation, and molecular events involved in photocarcinogenesis.
CLINICAL
VARIANTSCHARACTERIZATION SCHOPF-SCHULZ-PASSARGE
SYNDROME
Syndrome of cystic eyelids, palmo-plantar keratosis, hypodontia and hypotrichosis as a possible autosomal recessive trait.
Schopf E, Schulz HJ, Passarge E.
Birth Defects Orig Artic Ser. 1971 Jun;7(8):219-21. Abstract quote
Description is given of two sisters, offspring of a first cousin marriage, who exhibited the following identical lesions: 1) cysts of the borders of upper and lower lids; 2) hypodontia; 3) hypotrichosis; 4) palmo-plantar keratosis and 5) onychodystrophy.It is suggested that this combination represents a previously unrecognized autosomal recessive trait in man.
HISTOLOGICAL VARIANTS CHARACTERIZATION ADNEXAL CARCINOMA, LOW GRADE WITH DIVERGENT DIFFERENTIATION
Sikl's Department of Pathology, Charles University Medical Faculty Hospital, Pilsen, Czech Republic.
The conjoint occurrence of follicular, sebaceous, or apocrine differentiations in a cutaneous adnexal neoplasm is a known event, more often encountered in benign neoplasms, whereas reports of cutaneous malignant adnexal tumors with bilineage or trilineage differentiation are few.
A new case of a cutaneous malignant adnexal neoplasm with multidirectional differentiation is reported here. A 57-year-old woman presented with a long-standing, slowly growing, asymptomatic solitary tumor the size of a large nut in the coccygeal area, which was surgically excised. Ten years after the surgery, there was no evidence of recurrence or metastasis.
Microscopically, the neoplasm was located in the dermis with focal extension into the subcutis. It was asymmetric, horizontally oriented, and mostly composed of small nodules that varied in shape from round and oval aggregations to elongated strands and irregular islands; the nodules were either clustered, formed a jigsaw puzzle-like pattern or were dispersed. The nodules were composed of small basaloid cells sometimes intermixed with larger cells with ample cytoplasm forming glandular structures. Rare nodules resembled elements seen in a spiradenoma by containing scattered lymphocytes and globules of hyalinized eosinophilic basal membrane material. The stroma was paucicellular, but focally it resembled that seen in perifollicular mesenchyme. Mitotic figures, including abnormal ones, were infrequent, but mild nuclear pleomorphism, nuclear crowding, and individual cell necrosis were easily appreciable in both small basaloid cells and cells with clear cytoplasm. Perineural invasion was apparent.
We classified this tumor as a well-differentiated adnexal carcinoma demonstrating combined follicular and apocrine differentiation. It differs from previously published cases of malignant adnexal tumors with multidirectional differentiation and further exemplifies the spectrum of diversity encountered in malignant proliferations with differentiation toward the folliculosebaceous-apocrine unit.BASALOID FOLLICULAR HAMARTOMA
Familial basaloid follicular hamartoma: lesional characterization and review of the literature.Jih DM, Shapiro M, James WD, Levin M, Gelfand J, Williams PT, Oakey RJ, Fakharzadeh S, Seykora JT.
Am J Dermatopathol 2003 Apr;25(2):130-7 Abstract quote Basaloid follicular hamartoma (BFH) is a rare cutaneous lesion associated with the acquisition of small papules that remain stable for many years. Basaloid follicular hamartoma lesions can present sporadically or as part of an inherited syndrome. Occasionally, biopsies of BFH lesions are interpreted as basal cell carcinoma (BCC), which necessitates complete removal of the lesion.
In this report, we characterize a case of a familial BFH syndrome and discuss the clinical, histologic, and molecular features of BFH lesions that help to distinguish it from BCC. The BFH lesions in our patients remained stable for many years.
Histologically, BFH lesions exhibit fewer mitoses and decreased single cell necrosis when compared with BCC. Immunohistochemical staining for the proliferation markers proliferating cell nuclear antigen and Ki-67 demonstrated less staining in BFH than in BCC. In addition, levels of PTCH (patched) mRNA were increased relative to unremarkable epidermis in familial BFH lesions but to a lesser degree and in a different pattern than that seen in BCC. In summary, familial BFH can be distinguished from BCC based on clinical, histologic, and molecular features and is associated with deregulation of the PTCH pathway.
Basaloid follicular hamartoma may represent an indolent lesion within the spectrum of basaloid epithelial neoplasms associated with deregulation of the PTCH signaling pathway. We discuss this case in parallel with a growing body of literature that supports the nosologic designation of BFH.CHONDROID SYRINGOMA
- Chondroid syringoma. Cytokeratin 20 immunolocalization of Merkel cells and reappraisal of apocrine folliculo-sebaceous differentiation.
Salama ME, Azam M, Ma CK, Ormsby A, Zarbo RJ, Amin MB, Lee MW.
Department of Pathology, Henry Ford Hospital, Detroit, Mich 48202, USA.
Arch Pathol Lab Med. 2004 Sep;128(9):986-90. Abstract quote
CONTEXT: Chondroid syringoma (CS) is a benign cutaneous adnexal tumor with epithelial and stromal components. Epithelial components derived from folliculo-sebaceous-apocrine germ are evident in apocrine but not in eccrine CS.
OBJECTIVES: To further characterize pilosebaceous differentiation and to identify the presence of Merkel cells in the areas of follicular differentiation.
DESIGN: Histologic type, folliculo-sebaceous differentiation, character of stroma, and presence or absence of Merkel cells by cytokeratin (CK) 20 immunoreactivity were evaluated in 25 CSs (22 apocrine and 3 eccrine) from the surgical pathology files of Henry Ford Hospital (Detroit, Mich).
RESULTS: Most CSs occurred in the head and neck region of patients aged 40 years or older. We found no significant difference in sex, age, or location between apocrine and eccrine types. The stroma varied from myxoid (100%) to chondroid (59%), with various amounts of fat (59%) and ossification identified in 2 cases (9%) of apocrine type, but was homogeneously myxoid in the eccrine type. Follicular and sebaceous differentiation was found in 64% and 32% of apocrine CSs, respectively. Only 2 (14%) apocrine CSs with follicular differentiation were positive for CK20 (a few scattered cells in one case and numerous grouped cells in the other in association with follicular epithelium). No correlation was found between type of stroma and the presence of Merkel cells. Scattered Merkel cells were identified in 83% of normal hair follicles and in 33.3% of normal epidermis.
CONCLUSION: A high proportion of apocrine CSs show folliculo-sebaceous differentiation. The presence of Merkel cells in foci of follicular differentiation of CS supports the hypothesis that Merkel cells may be an integral constituent of follicles. To our knowledge, the presence of Merkel cells in CS, particularly in proliferative form, has not been described previously in the literature.CLEAR CELL MESENCHYMAL NEOPLASM
- Distinctive dermal clear cell mesenchymal neoplasm: clinicopathologic analysis of five cases.
Lazar AJ, Fletcher CD.
Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA.
Am J Dermatopathol. 2004 Aug;26(4):273-9. Abstract quote
Dermal clear cell tumors are not common. This group of lesions is comprised primarily of clear cell adnexal lesions, balloon cell melanocytic lesions, and metastatic clear cell carcinomas.
We report the clinicopathologic features of five cases of a novel dermal clear cell neoplasm that appears mesenchymal in nature. The affected patients included 3 men and 2 women ranging in age from 38 to 70 (median, 45 years). All the lesions occurred on the lower limb. Clinically described as smooth cutaneous nodules, size ranged from 0.5 to 2.5 cm in greatest dimension and the lesions were present from weeks to 5 years prior to excision. Situated in the reticular dermis, the tumors usually extended to involve the subcutis with sparing of the papillary dermis. The tumors were composed of large optically clear cells with vesicular nuclei. The lesions entrapped adnexal structures and thin dermal collagen fibers. Mitoses were rare (less than 1 per 25 hpf). A single case showed more pleomorphic nuclei as well as quite frequent mitoses and was considered of uncertain biologic potential. Immunohistochemistry revealed reactivity only for NKI-C3 (5/5 cases), CD68 (2/5 cases), and vimentin (2/3 cases); melanocytic, epithelial, and lymphoid markers were uniformly negative. All five lesions were locally excised; the more pleomorphic and mitotically active lesion was widely re-excised and given subsequent radiation therapy. In follow-up ranging from 1.5 to 11 years (median, 5.5 years), none of these lesions has recurred.
These tumors appear to be mesenchymal in nature, but their precise line of differentiation is unknown. Recognition of these lesions is important to avoid confusion with better-known malignant neoplasms.CONGENITAL PANFOLLICULAR NEVUS
- Congenital panfollicular nevus: report of a new entity.
Finn LS, Argenyi ZB.
The Department of Pathology at The University of Washington, Seattle, WA, USA.
J Cutan Pathol. 2005 Jan;32(1):59-62. Abstract quote
The various forms of non-melanocytic nevi (hamartomas) are usually encountered in pediatric patients, and nevus sebaceous of Jadassohn is the most common to have undifferentiated pilosebaceous units.
We report a unique congenital follicular nevus that fails to meet the criteria of any previously described follicular neoplasm, despite the plethora of alternatives. Clinically considered a syringocystadenoma papilliferum, the excised lesion contained multiple dermal nodules that exhibited nearly all stages of follicular differentiation. The periodicity of the follicular proliferations was akin to normal terminal hair, and a prominent perifollicular sheath surrounded each.
This benign lesion of abortive hair follicles was unassociated with any established genodermatous syndrome or other adnexal neoplasm.GIANT FOLLICULO-SEBACEOUS CYSTIC HAMARTOMA
Giant folliculosebaceous cystic hamartoma of the upper extremity
David E. Sturtz, David J. Smith, Marlene S. Calderon and Douglas R. Fullen
Journal of Cutaneous Pathology
Volume 31 Issue 3 Page 287 - March 2004 Abstract quote
Background: Folliculosebaceous cystic hamartoma (FSCH) is a rare cutaneous hamartoma consisting of dilated folliculosebaceous units invested in mesenchymal elements. These lesions have a striking predilection for the central face and scalp of adults. The vast majority of lesions present as 0.5-1.5-cm papules or exophytic nodules. A single case of giant FSCH has been reported on the upper back.Methods: A 32-year-old woman presented with a (15 cm in greatest dimension) plaque-like, multinodular lesion on her left upper arm for several years. The lesion was clinically suspected to be a nevus sebaceus.
Results: The skin excision showed numerous dermal and subcutaneous dilated follicular structures with peripherally radiating sebaceous lobules, hair follicles, and surrounding mesenchymal elements consistent with FSCH.
Conclusion: To our knowledge, this is the second case of giant FSCH. Our case is unique for its larger size, more plaque-like growth, and location on an extremity when compared to the seminal case of giant FSCH.
LYMPHOEPITHELIOMA-LIKE CARCINOMA
Am J Dermatopathol. 2006 Jun;28(3):211-215. Abstract quote
We report a case of a primary lymphoepithelioma-like carcinoma (LELC) of the skin. The patient was a 73-year-old man with a lump on his back for 18 months. A biopsy and subsequent excision was performed. He also had axillary node clearance for metastatic disease. The tumor was composed of islands of pleomorphic cells with a lymphocytic infiltrate.
Differential diagnoses included squamous cell carcinoma, adnexal carcinoma, Merkel cell tumors, lymphoepithelial lesions, lymphomas, and skin metastases. The histopathologic and immunohistochemical features were those of a LELC of the skin. It was negative for Epstein-Barr virus. Just over 30 cases of primary LELCs arising in the skin have been reported with only 1 documented fatality.
We report a case with extensive vascular involvement and bilateral lymph node metastases.
- Lymphoepithelioma-Like Carcinoma of the Skin in a Tunisian Patient.
Fenniche S, Zidi Y, Tekaya NB, Ammar FB, Yaacoub K, Mokni M, Mokhtar I, Osman AB, Zitouna MM, Haouet S.
From the *Dermatology Department, Habib Thameur Hospital, Tunis, Tunisia; daggerHistopathology Department, La Rabta Hospital, Tunis, Tunisia; double daggerDermatology Department, La Rabta Hospital, Tunis, Tunisia; and section signORL Department, La Rabta Hospital, Tunis, Tunisia.
Am J Dermatopathol. 2006 Feb;28(1):40-44. Abstract quote
Lymphoepithelioma-like carcinoma of the skin (LELCs) is a rare cutaneous neoplasm with histologic features resembling lymphoepitheliomatous tumors of the nasopharynx. The association of lymphoepitheliomas with Epstein-Barr Virus (EBV) at some extracutaneous sites is well documented. In contrast, the presence of EBV in LELCs has never been shown in either Caucasians or Asian patients.
We present the first case of LELCs in a Tunisian patient, a 78-year-old woman who presented with a nodule of the right cheek of 2 months' duration. The patient underwent surgical excision and there was no evidence of local recurrence 6 months later.
Histologically, the entire dermis was occupied by lobules composed of atypical epithelial cells surrounded by a dense lymphoplasmacytic infiltrate. Immunohistochemical examination showed that the epithelial tumor cells were positive for cytokeratin and epithelial membrane antigen. In situ hybridization investigations for the presence of EBV-encoded RNA showed negative results.
Our findings suggest that LELCs is not related to EBV among North African patients.
- Lymphoepithelioma-like carcinoma of the skin with spindle cell differentiation.
Clarke LE, Ioffreda MD.
Department of Pathology, Penn State Univerity of Medicine/Hershey Medical Centre, Hershey, PA, USA.
J Cutan Pathol. 2005 Jul;32(6):419-23. Abstract quote
Background: Primary cutaneous LELC is a cutaneous neoplasm with histopathologic features identical to those seen in the undifferentiated subtype of nasopharyngeal carcinoma. It is extremely rare, with only approximately 30 cases reported in the literature.
Methods: We report a case of primary cutaneous LELC arising on the forehead of a 72 year-old male in which a proportion of the neoplastic cells demonstrated distinctive spindle cell morphology.
Results: Microscopic examination showed a dense lymphoplasmacytic infiltrate admixed with large spindle-shaped cells with vesicular nuclei, prominent nucleoli, and frequent mitotic figures. These cells were negative for an extensive panel of immunohistochemical markers and positive only for broad-spectrum cytokeratins and epithelial membrane antigen. There was no connection between the tumor and the epidermis and no epidermal dysplasia. In situ hybridization for Epstein-Barr virus was negative.
Conclusions: The spindle cell differentiation in this case is unusual and suggests that in some cases the differential diagnosis of cutaneous spindle cell neoplasms might include primary cutaneous LELC.NEUROFOLLICULAR HAMARTOMA Neurofollicular hamartoma: a light microscopic and immunohistochemical study.
Barr RJ, Goodman MM.
Department of Dermatology, University of California, Irvine.
J Cutan Pathol 1989 Dec;16(6):336-41 Abstract quote
Neurofollicular hamartoma is an unusual, previously undescribed neoplasm characterized by a proliferation of spindle cells and hyperplastic pilosebaceous units.
Five cases were reviewed. The lesions presented as single, asymptomatic, smooth, flesh-colored papules. Four were on the nose, and one on the adjacent nasolabial fold. Immunoperoxidase studies performed on two cases utilizing antibodies to S-100 antigen were positive in both.
These lesions share some histological and clinical features with angiofibroma and neurofibroma.
NODULAR HIDRADENOMA
Section of Histopathology, Department of Pathology and Microbiology, The Aga Khan University Medical Centre, Karachi, Pakistan.
Background: Nodular hidradenoma is a distinctive sweat gland neoplasm. In addition to the well-known histological and cytological features, we hereby describe for the first time nuclear grooving as a useful morphological feature to aid in its diagnosis.
Methods: All cases were analyzed for anatomic location, size, age, sex and histology, with attention focused mainly on the nuclear features. A semiquantitative method was used to estimate the percentage of nuclear grooves in five consecutive high-power fields (x40), with confirmation on x100. Electron microscopy was also performed to confirm light microscopic observation.
Results: Totally, 34 cases of nodular hidradenoma were studied. All the tumors showed two types of cells. One type of cell contained clear cytoplasm with small, round nuclei. The second type of cell, which was the predominant type, had elongated nuclei. In 30 (88%) of the 34 cases, about 30% of these cells at x40 and x100 magnification showed nuclear grooving. Electron microscopy on these samples confirmed nuclear grooves.
Conclusions: In this study, we reviewed 34 cases of nodular hidradenoma. In addition to the classical features, both histologically and cytologically, we describe for the first time the nuclear grooves as a frequent finding in these neoplasms. This finding was also confirmed by electron microscopy. We believe that this newly described histological feature will aid the practicing pathologist to make this important diagnosis.PANFOLLICULOMA
- Cystic panfolliculoma.
Hoang MP, Levenson BM.
Department of Pathology, The University of Texas Southwestern Medical Center, Dallas, TX 75390-9073, USA.
Arch Pathol Lab Med. 2006 Mar;130(3):389-92. Abstract quote
Panfolliculoma is a rare follicular neoplasm with differentiation toward both upper (infundibulum and isthmus) and lower (stem, hair matrix, and bulb) segments of a hair follicle.
We present an unusual case of cystic panfolliculoma. A 33-year-old Hispanic woman presented with an 8-month history of a 3.0-cm cystic scalp mass. The lesion was excised, and the histologic sections showed a cystic follicular neoplasm that contained corneocytes in basket-woven and laminated array, trichohyalin granules of the inner root sheath, germinative cells, papillae, matrical cells, and "shadow" cells.
Cytokeratin 903 and cytokeratin 5/6 immunostains uniformly highlight the tumor cells. Ber-EP4 strongly labels the germinative cells but not the follicular papillae. CD34 labels the surrounding fibrotic stroma and focally the epithelial component.
SARCOMATOID CARCINOMA
- Cutaneous carcinosarcoma: adnexal vs. epidermal types define high- and low-risk tumors. Results of a meta-analysis.
Tran TA, Muller S, Chaudahri PJ, Carlson JA.
Department of Pathology, Florida Orlando Hospital, Orlando, FL.
J Cutan Pathol. 2005 Jan;32(1):2-11. Abstract quote
Objective: We report four cases of cutaneous carcinosarcoma (CS) and perform a meta-analysis of the cutaneous CS literature.
Results: CS occurred in elderly patients (mean of 80 years) on sun-damaged skin, and were keratotic papules of short duration. They did not recur after excision. CS exhibited basal cell carcinoma mixed with atypical fibroxanthoma cell populations. Immunophenotyping revealed vimentin+/keratin- spindle cells and vimentin-/keratin+ epithelial cells. Three cases exhibited p53 protein expression of both carcinomatous and sarcomatous components. Literature review identified 38 cases of cutaneous CS that could be broadly classified into two distinct groups. Epidermal-derived (basal or squamous cell carcinoma epithelial component) CS arose on the sun-damaged skin of the head and neck of elderly males (mean age 72 years) and had a 70% 5-year disease-free survival. In contrast, adnexal CS (spiradenocarcinoma, porocarcinoma, proliferating tricholemmal cystic carcinoma, or matrical carcinoma) occurred in younger patients (mean age 58 years), showed recent growth in a long-standing nodule and had a 25% 5-year disease-free survival. Age less than 65 years, recent growth, long-standing skin tumor, and tumor size greater than 2 cm significantly correlated with poor outcome.
Conclusions: Cutaneous CS is an aggressive skin cancer with high risk for advanced disease. Significant risk factors exist whose identification will allow for better management of CS patients.
Monophasic sarcomatoid carcinoma of the scalp: a case mimicking inflammatory myofibroblastic tumor and a review of cutaneous spindle cell tumors with myofibroblastic differentiation.Winfield HL, Rosenberg AS, Antonescu CR, Weil M, Wang AR.
Tulane University Health Sciences Center, New Orleans, LA, USA, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
J Cutan Pathol. 2003 Jul;30(6):393-400. Abstract quote BACKGROUND: The evaluation of malignant cutaneous spindle cell tumors is challenged by a diagnostic differential that comprises neoplasms of diverse histogenesis, and a broad immunohistochemical panel may confound the diagnosis when the results suggest multiple lines of differentiation, such as with a combined myofibroblastic and epithelial phenotype.
METHODS: We report the case of a solitary scalp nodule that quickly became locally metastatic. A comprehensive panel of immunohistochemistry markers and electron microscopy was evaluated to determine the differentiation of the spindle cells.
RESULTS: The tumor, consisting of wavy and slender spindle cells with predominantly bland nuclei, showed immunoreactivity to vimentin, smooth muscle actin, and muscle-specific actin. AE1/AE3, CK5/6, and MNF-116 antibodies were weakly positive in rare cells. However, 34betaE12 showed diffuse positivity in the spindle cell population, thus supporting the diagnosis of a sarcomatoid carcinoma with myofibroblastic differentiation.
CONCLUSIONS: The use of 34betaE12 is essential for the evaluation of myofibroblastic spindle cell tumors with rare cytokeratin reactivity. However, even with immunohistochemical and electron microscopic studies, the diagnosis of spindle cell tumors can be confounded by the multiplicity of nosologic equivalents, such as carcinosarcoma, spindle cell carcinoma, and metaplastic carcinoma. The nomenclature of these spindle cell tumors is discussed.
SPECIAL STAINS/
IMMUNOPEROXIDASEGENERAL Expression profiles of p63, p53, survivin, and hTERT in skin tumors.
Park HR, Min SK, Cho HD, Kim KH, Shin HS, Park YE.
Department of Pathology, College of Medicine, Hallym University, Anyang, Korea.
J Cutan Pathol. 2004 Sep;31(8):544-9. Abstract quote
Background: p63 is a p53 homolog and a marker expressed in replicating keratinocytes. Survivin is a recently characterized inhibitor of apoptosis protein that is abundantly expressed in most solid and hematologic malignancies. Telomerase reverse transcriptase (TERT) is the major determinant of human telomerase activity, and its expression is indicative of unlimited replication. We herein evaluated the expression profiles of p63, p53, survivin, and hTERT in usual skin cancers, including squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) and putative preneoplastic epidermal lesions, including actinic keratosis (AK), Bowen's diasease, and porokeratosis.
Methods: Immunohistochemistry using antibodies against p63, p53, survivin, and hTERT was performed. Semi-quantitative evaluation (-, +, 2+, 3+) was carried out.
Results: BCCs showed diffuse p63 expression and SCCs heterogeneous p63 expression with negativity in terminally differentiated squamous cells. All preneoplastic epidermal lesions showed p63 expression in all cell layers. p53 was found in seven of 10 cases of BCCs, all 10 cases of SCCs, and nine of 10 cases of Bowen's disease. AK and porokeratosis revealed focal to moderate p53 expression. Survivin was found in eight of 10 cases of SCCs and eight of 10 cases of Bowen's disease. Six of 10 cases of BCCs revealed weak survivin positivity. AK and porokeratosis showed survivin expression confined to the basal layer. hTERT expression was found in most cases of skin cancers and preneoplastic lesions.
Conclusions: p63 expression may be a marker of basal/progenitor cells and a diagnostic marker in skin tumors. p63 expression is not related to p53 expression in these tumors. This study points to a putative role of survivin and hTERT in the development of certain skin cancers. In addition, our data support the concept of porokeratosis being a premalignant condition.
The diagnostic utility of p63, CK5/6, CK 7, and CK 20 in distinguishing primary cutaneous adnexal neoplasms from metastatic carcinomas.
Qureshi HS, Ormsby AH, Lee MW, Zarbo RJ, Ma CK.
Department of Pathology, Henry Ford Hospital, Detroit, MI, USA.
J Cutan Pathol. 2004 Feb;31(2):145-52. Abstract quote
BACKGROUND: Distinguishing primary cutaneous adnexal neoplasms (PCANs) from metastatic carcinomas (MCs) can be difficult. We study the utility of p63, CK 5/6, CK 7, and 20 expression in PCAN vs. MC.
METHODS: Twenty-one PCAN with sweat gland differentiation (six benign, 15 malignant), one sebaceous carcinoma, and 15 MC (14 adenocarcinomas, one urothelial carcinoma) to skin were retrieved from the pathology files. Immunostains for p63, CK 5/6, CK 7, and CK 20 were performed and graded as follows: 1, <10; 2, 11-50; and 3 >50% of tumor cells stained.
RESULTS: Twenty of 22 PCAN expressed p63 and CK 5/6. Four of 15 and two of 15 MC were positive for CK 5/6 and p63, respectively. Thirteen of 22 PCAN and 13 of 15 MC were positive for CK 7, respectively. All PCAN were negative for CK 20, two of 15 MC were positive. The sensitivity and specificity for the diagnosis of PCAN were 91 and 73% for CK 5/6, 91 and 100% for p63, and 60 and 13% for CK 7, respectively.CONCLUSIONS: For distinguishing PCAN from MC: (1) positivity for p63 and CK 5/6 are relatively specific and sensitive for PCAN, (2) CK 7 and 20 are neither sensitive nor specific, and (3) CK 7 positivity in PCAN was focal with a specific pattern in contrast to the diffuse positivity for MC.
CD5
- Cluster designation 5 staining of normal and non-lymphoid neoplastic skin
Bogner PN, Su LD, Fullen DR.
Department of Pathology, University of Michigan Medical Center, Ann Arbor, MI, USA.
J Cutan Pathol. 2005 Jan;32(1):50-4. Abstract quote
Background: Immunohistochemical staining for cluster designation 5 (CD5) has been found to label a variety of non-lymphoid tumors.
Methods: A variety of eccrine, apocrine, follicular, epithelial, and pagetoid lesions were selected and stained with an anti-CD5 monoclonal antibody (Novocastra Labs, Newcastle upon Tyne, UK, clone 4C7) by immunohistochemistry. The intensity of positive cytoplasmic staining was graded semiquantitatively (1+ weak staining, 2+ strong staining). Additionally, the percentage of positive lesional cells was placed in one of four categories: >75%, 25-75%, 1-25%, and <1%.
Results: Within normal skin, CD5 labeled lymphocytes, apocrine glands, deep dermal eccrine glands, and smooth muscle (weak). The majority of benign and malignant apocrine lesions demonstrated strong focal (36%, n = 11)-to-diffuse (64%, n = 16) staining. In contrast, labeling of benign eccrine tumors was more focal, tending to localize around ducts (79%, n = 19). Microcystic adnexal carcinoma demonstrated focal staining of deeper ductal structures (71%, n = 7), whereas desmoplastic trichoepithelioma and basal cell carcinoma showed only rare positive cells. All cases of mammary (n = 7) and extramammary (n = 8) Paget's disease labeled diffusely for CD5. Pagetoid Bowen's disease (n = 6), intraepidermal sebaceous carcinoma (n = 3), nor melanoma in situ (n = 6) showed any CD5 staining.
Conclusions: Immunohistochemical staining for CD5 is extremely useful in the differential diagnosis of pagetoid epidermal lesions and will mark mammary and extramammary Paget's disease, but not pagetoid Bowen's disease, melanoma in situ, or sebaceous carcinoma.CD10
- CD10 is expressed in cutaneous clear cell lesions of different histogenesis.
Perna AG, Smith MJ, Krishnan B, Reed JA.
Department of Pathology, Baylor College of Medicine, Houston, Texas.
J Cutan Pathol. 2005 May;32(5):348-51. Abstract quote
Background: CD10, the Common Acute Lymphoblastic Leukemia Antigen, is a neutral endopeptidase commonly used as a marker of early B-cell differentiation in the classification of lymphomas. Neoplasms of other histogenesis may express CD10, including renal cell carcinoma. Renal cell carcinoma metastatic to the skin (MRCC) can simulate other more common clear cell lesions in which expression of CD10 has not been described.
Methods: Fifty-two cutaneous clear cell lesions including xanthomas (CX), xanthelasmas (XA), xanthogranulomas (XG), balloon cell nevi (BCN), nodular/clear cell hidradenomas (CCH), and MRCC were examined by immunohistochemistry for the expression of CD10, noting frequency and pattern of labeling.
Results: CD10 was expressed in 32/35 of the xanthomatous lesions (CX, XA, and XG), 3/3 MRCC, but only 2/8 BCN and 2/6 CCH. BCN and CCH expressed CD10 in fewer than 10% of the clear cells, whereas all MRCC and most xanthomatous lesions had labeling in greater than 10% (p < 0.001). Xanthomatous lesions exhibited a predominantly membranous pattern of labeling compared to the cytoplasmic pattern of MRCC (p < 0.025).
Conclusions: Cutaneous clear cell lesions of different histogenesis express CD10, limiting its use as a specific diagnostic marker for MRCC. Among other clear cell lesions, however, BCN and CCH have a lower frequency of labeling than does MRCC, and xanthomatous lesions show a membranous pattern compared to the cytoplasmic pattern of MRCC, BCN, and CCH. This latter observation may be indicative of altered protein function or trafficking.
DIFFERENTIAL DIAGNOSIS CHARACTERIZATION CUTANEOUS HORN Cutaneous horns of the eyelid: a clinicopathological study of 48 cases.
Mencia-Gutierrez E, Gutierrez-Diaz E, Redondo-Marcos I, Ricoy JR, Garcia-Torre JP.
Department of Ophthalmology, 12 de Octubre Hospital, Complutense University, Madrid, Spain.
J Cutan Pathol. 2004 Sep;31(8):539-43. Abstract quote
Background: Cutaneous horn (cornu cutaneum) is a morphological designation for a protuberant mass of keratin that resembles the horn of an animal. It results from unusual cohesiveness of keratinized material from the superficial layers of the skin or implanted deeply in the cutis. This lesion may be associated with a benign, premalignant, or malignant lesion at the base, masking numerous conditions.
Methods: A retrospective analysis of 48 cases of cutaneous horns of the eyelid treated between 1992 and 2002 has been performed.
Results: Twenty-four men and 19 women, with a mean age of 62 years (range 16-90), were treated by surgery. Histologically, 77.1% were associated with benign specimens at the base pathology, 14.6% were premalignant, and finally, 8.3% were caused by malignant skin tumors. The most common lesion was seborrheic keratosis among the benign lesions, actinic keratosis among the premalignant ones, and basal cell carcinoma and squamous cell carcinoma among the malignant ones.
Conclusion: Cutaneous horns usually appear on exposed skin areas in elderly men. The important issue in this condition is not the horn itself, which is just dead keratin, but rather the nature of the underlying disease, although the horns are usually benign.
Gigantic cutaneous horns of the scalp: lesions with a gross similarity to the horns of animals: a report of four cases.Michal M, Bisceglia M, Di Mattia A, Requena L, Fanburg-Smith JC, Mukensnabl P, Hes O, Cada F.
Department of Pathology, Laborator Spec. Diagnostiky Medical Faculty Hospital, Pilsen, Czech Republic.
Am J Surg Pathol 2002 Jun;26(6):789-94 Abstract quote Gigantic cutaneous horns, grossly similar to the horns seen in animals, are exceedingly rare in humans. After finding one case in practice, we searched our departmental files for similar cases and examined them grossly and microscopically.
Four cases were identified. All occurred as solitary lesions in older women on the parietal-occipital region of the scalp. They had a growth history of up to 30 years; the women hid these horns in their hair.
Grossly, the horns were yellow-grey, and there were shallow furrows running along the length of the horns. The length ranged from 17 to 25 cm, and the width was up to 2.5 cm. All four lesions showed similar histologic changes. Microscopically, the gigantic horns consisted of a mixture of squamous epithelial cells and tricholemmal keratinized debris. In one case the base of the horn was directly connected with a mass composed of benign tricholemmal cysts of the scalp. Mitoses were common, but atypical mitoses were not observed. The nuclei of the squamous cells were bland without pleomorphism, hyperchromasia, or atypia.
Follow-up of all patients was uneventful: all patients were well and without signs of recurrence or metastasis 2-15 years after the surgical excision.
Gigantic cutaneous horns are rare and benign. We think that they represent an extremely well-differentiated variant of proliferating tricholemmal tumor with an unusual and remarkable gross pattern.
ECCRINE NEVUS Eccrine nevus presenting as a perianal skin tag: a case report and review of the literature.
Mahdavy M, Smoller BR.
Departments of Pathology (M.M., B.R.S.) and Dermatology (B.R.S.), University of Arkansas for Medical Sciences, Little Rock, Arkansas, U.S.A.
Am J Dermatopathol 2002 Aug;24(4):361-3 Abstract quote We present the case of a 9-year-old girl with a perianal skin tag. This asymptomatic lesion was removed for cosmetic reasons and demonstrated a polypoid lesion with a slightly acanthotic epidermis.
The dermis was filled with mature-appearing eccrine ducts and glands but with no other cutaneous appendages, adipocytes, or abnormal vascularity. We believe this to represent a polypoid eccrine nevus and that its presentation is unique.
ECTOPIC BREAST TISSUE Ectopic breast tissue and breast-like sweat gland metaplasias: an overlapping spectrum of lesions.
Pfeifer JD, Barr RJ, Wick MR
Depar