Expression of stem cell markers nestin and cytokeratin 15 and 19 in cutaneous malignancies.

BACKGROUND: Emerging evidence is implicating stem cells in the pathogenesis of different cutaneous neoplasms. The immunohistochemical use of stem cell markers has facilitated stem cell identification. While few studies have examined the expression of cytokertatin (CK)15 and cytokeratin (CK)19 in basal cell carcinoma (BCC) and squamous cell carcinoma (SCC), only rarely have nestin expression been examined in these two malignancies. Furthermore, stem cell marker expression, to the best of our knowledge, has not been examined in Merkel cell carcinoma (MCC). METHODS: In this study, we examined the expression of stem cell markers CK15, CK19 and nestin in 51 overall cases (11 cases of MCC and 20 cases each of BCC and SCC) retrieved from the pathology files of Skin Pathology Laboratory, Boston University School of Medicine. RESULTS: Cytokeratin 15 immunoreactivity was observed in 30% of BCC cases and only a single (5%) SCC case, while all MCC cases were negative. While 60% of BCC cases and 30% of SCC cases stained positively with CK19, all MCC cases showed positive immunostaining in a dot-like pattern. While negative in BCC and MCC, nestin expression was interestingly seen in 45% of SCC cases. CONCLUSIONS: Our study described the expression profiles of stem cell markers CK15, CK19 and nestin in BCC, SCC and MCC. In addition to confirming results of the previous reports, our study also showed positive nestin expression in around half of SCC cases, which adds this malignancy to the cutaneous tumours that have been so far reported to exhibit nestin expression.

RAS and RAF mutations in banal melanocytic aggregates contiguous with primary cutaneous melanoma: clues to melanomagenesis.

BACKGROUND: Distinguishing banal melanocytic aggregates contiguous with malignant melanoma can be a histological challenge but is essential because of the potential for a spurious Breslow measurement. OBJECTIVES: Our aim was to ascertain whether the histological distinction between the two relates to differences in the prevalence of mutations in genes significant in melanomagenesis. METHODS: Mutations in BRAF codon 600, NRAS1 codons 12/13, NRAS2 codons 60/61 and KRAS codons 12/13 were ascertained in 18 cases of primary cutaneous malignant melanoma contiguous with banal melanocytic aggregates using laser capture microdissection. RESULTS: Overall, 12 of 18 cases (67%) exhibited a mutation in at least one gene. BRAF V600E appeared to be the most commonly mutated gene in both the melanocytic aggregate (seven of 18, 39%) and the melanoma (four of 18, 22%). Both populations demonstrated a similar BRAF genomic profile in 11 of 18 cases (61%) (two BRAF V600E, nine BRAF-WT), a similar KRAS genomic profile in 14 of 18 cases (78%) (one KRAS G12V, 13 KRAS-WT) and a similar NRAS2 genomic profile in 14 of 18 cases (all WT). Of interest, we noted a relatively high prevalence of KRAS mutations (five of 18, 28%). The frequency of KRAS mutations in the melanocytic aggregate (five of 18, 28%) was second to BRAF V600E, while in melanoma, the frequency was also second to BRAF V600E but equalled that of NRAS2 (1 of 18, 6%). No NRAS1 mutations were observed. BRAF and RAS mutations appeared to be mutually exclusive with only three of 18 cases (17%) demonstrating a mutation in both genes (melanocytic aggregate only). CONCLUSIONS: Our findings hint towards the interpretation of banal melanocytic aggregates serving as precursor lesions.

Porokeratosis ptychotropica: a lesser-known variant.

We report a case of the rare porokeratosis variant porokeratosis ptychotropica (PP). A circumferential perianal plaque and the characteristic histology of multiple cornoid lamellae with underlying dermal amyloid deposition were seen. Amyloid deposition was seen in the biopsied intertriginous area of the plaque only, which, in concordance with other cutaneous amyloid deposition disorders, may suggest a role for friction in the pathogenesis of this histological finding. We review the literature on PP and summarize the poor response seen to treatments.

Cutaneous neuroendocrine adenoma: an uncommon neoplasm.

BACKGROUND: Cutaneous neuroendocrine neoplasms are typically malignant. Benign cutaneous neuroendocrine tumors are uncommon. METHODS: We report the case of a 32-year-old female who presented with a granular mass in the right external auditory canal. RESULTS: Microscopic examination of a shave biopsy revealed a poorly circumscribed neoplasm with glandular differentiation. While cytologic atypia and mitotic activity were not evident, pagetoid spread was observed. Immunohistochemistry was indicative of neuroendocrine origin. CONCLUSIONS: This case report of neuroendocrine adenoma indicates that this entity should be entertained in the repertoire of conditions affecting the external ear.

Multiple cellular neurothekeomas--a case report and review on the role of immunohistochemistry as a histologic adjunct.

BACKGROUND: Cellular neurothekeoma is a relatively rare, benign cutaneous neoplasm, which usually presents as a solitary papule or nodule involving the head and neck area of young adults. Multiple neurothekeomas have not, to date, been known to occur. METHODS: We report a 30-year-old, otherwise healthy, male who presented with multiple neurothekeomas (15) in the head and neck area over a period of 12 years. RESULTS: While the unifying feature of all biopsied (10 of 15) lesions was the presence of epithelioid cells--the lesions differed in their cellularity and the degree of sclerosis of the stromal component. Antigenic profiling of the lesional cells revealed expression of vimentin, NKI/C3, PGP 9.5, factor XIIIa and CD68 but not S100, HMB45, MelanA, EMA, MSA, desmin, CD57 or NGF-R. CONCLUSIONS: This case report is the first to document the occurrence of multiple cellular neurothekeomas. An unusual histologic feature of some of the biopsied lesions was the presence of a markedly sclerotic stroma.

Metastatic papillary carcinoma of the thyroid.

BACKGROUND: Cutaneous metastases from thyroid carcinomas, although uncommon, have been previously reported and are usually found in association with evidence of disseminated disease. METHODS: We report a 75-year-old male who presented with a 4-cm reddish violaceous nodule on the left temple and a clinical history significant for papillary carcinoma of the thyroid. RESULTS: Microscopic examination of a 4-mm punch biopsy revealed a poorly circumscribed neoplasm with focal epidermal connection and multiple cystic cavities and papillary projections. CONCLUSIONS: This case report describes a solitary cutaneous lesion as the first evidence of disseminated neoplastic disease in a patient with no other clinical evidence of concurrent metastases. The histology of the lesion was unusual in that it mimicked a primary cutaneous neoplasm.

Cutaneous anaplastic large cell lymphoma--a case report.

Cutaneous involvement in anaplastic large cell lymphoma may be in the form of primary cutaneous disease (primary cutaneous anaplastic large cell lymphoma) or secondary to involvement by systemic disease (systemic anaplastic large cell lymphoma). This case report, an example of the latter, describes a solitary cutaneous lesion as the first evidence of disseminated neoplastic disease. The histology of the lesion was identical to its primary cutaneous counterpart.

Tazarotene cream for the treatment of facial photodamage: a multicenter, investigator-masked, randomized, vehicle-controlled, parallel comparison of 0.01%, 0.025%, 0.05%, and 0.1% tazarotene creams with 0.05% tretinoin emollient cream applied once daily for 24 weeks.

OBJECTIVE: To assess the safety and efficacy of 4 concentrations of tazarotene cream in the treatment of facial photodamage. DESIGN: Prospective weekly multicenter, investigator-masked, randomized, parallel-group study. SETTING: University hospitals and clinical research centers. PATIENTS: Three hundred forty-nine subjects with facial photodamage. INTERVENTION: Daily topical application of tazarotene cream (0.01%, 0.025%, 0.05%, and 0.1%) compared with its vehicle and with 0.05% tretinoin emollient cream. RESULTS: Tazarotene cream and tretinoin cream significantly improved mottled hyperpigmentation and fine wrinkles. At week 24, treatment success rates based on global responses were 67% (39 of 58 subjects) with 0.1% tazarotene, 52% (30 of 58 subjects) with 0.05% tazarotene, 36% (21 of 58 subjects) with 0.025% tazarotene, 41% (24 of 59 subjects) with 0.01% tazarotene, 55% (32 of 58 subjects) with 0.05% tretinoin, and 22% (13 of 58 subjects) with vehicle. Local adverse events, although more frequent with tazarotene at higher concentrations, were generally mild to moderate. CONCLUSIONS: Tazarotene in a cream formulation is safe and is associated with positive changes in the treatment of photodamaged facial skin.

New insights into the applicability of T-cell receptor gamma gene rearrangement analysis in cutaneous T-cell lymphoma.

BACKGROUND: Detection of clonal T-cell receptor (TCR) gamma gene rearrangement by polymerase chain reaction (PCR) based method is a marker for cutaneous T-cell lymphoma (CTCL) although it can be seen in some benign dermatoses. To determine the accuracy of histologic criteria alone as well as the adjuvant diagnostic role of TCR gene rearrangement for the diagnosis of CTCL, we studied 100 patients with cutaneous T-cell infiltrates by both histology and TCR gene rearrangement. METHODS: The histologic features of the 100 patients were first reviewed by two independent dermatopathologists and their confidence in the diagnosis of CTCL was assigned one of four levels. Then the specimens were analyzed for TCR gene rearrangement either on paraffin-embedded or fresh-frozen tissue by PCR/denaturing gradient gel electrophoresis (DGGE). RESULTS: The clonality was detected in 100% (15/15) diagnostic of, 84.6% (11/13) consistent with, 57.6% (19/33) suggestive of CTCL. In 9 cases TCR gene rearrangement was compared between formalin-fixed and fresh specimens of the same individual, but with different degrees of histologic confidence (no lower than suggestive). In all cases fresh specimens were positive. In 5 of the cases (2-diagnostic, 2-consistent, 1-suggestive) formalin-fixed specimens were positive as well, and in 4 cases (1-consistent, 3-suggestive) formalin-fixed specimens were negative. When TCR gene rearrangement was studied in eight cases on sequential biopsies from the same patient, the clonality was detected in only one or two biopsies in four cases in which the histologic confidence was low (suggestive or nondiagnostic). The TCR gene rearrangement study showed identical banding patterns in lesions from different clinical stages in most patients. However, we observed that in one case, oligoclonal-banding pattern was seen in initial biopsy with histopathologic consistent with CTCL, while monoclonal banding pattern in more advanced lesion. CONCLUSIONS: Our data have demonstrated that TCR gene rearrangement studies by PCR/DGGE are consistently positive regardless of tissue fixation (formalin-fixed, paraffin-embedded vs. fresh-frozen tissue) and biopsy site when the histologic degree of confidence is very high (diagnostic). So, it may be of less importance as an adjuvant to histopathologic diagnosis for the cases with diagnostic CTCL histology. However, TCR gene rearrangement studies are particularly important in earlier cases with less conclusive histology, which provides strong confirmatory evidence of an evolving CTCL. In these cases, multiple biopsies may be required to establish the diagnosis and analysis of fresh tissue is suggested to increases the sensitivity. Moreover, our observation also suggested that some CTCL might not be monoclonal de novo, but oligoclonal instead.

Laser resurfacing-induced hypopigmentation: histologic alterations and repigmentation with topical photochemotherapy.

BACKGROUND: Hypopigmentation is a relatively common side effect of CO2 laser resurfacing. Little is known regarding the histologic features of the areas of pigmentation loss. To date, hypopigmentation is considered a permanent complication of this procedure. OBJECTIVE: To assess the histologic features of hypopigmentation caused by laser resurfacing and to evaluate the efficacy and safety of topical psoralen photochemotherapy. METHODS: Ten patients were included in this pilot study. Four had baseline biopsies performed. Histologic parameters assessed included epidermal melanin, dermal melanophages, perivascular inflammation, Mel-5 immunostaining for melanocytes, and dermal fibrosis. Seven patients were treated twice a week with topical photochemotherapy utilizing 0.001% 8-methoxypsoralen. RESULTS: All of the biopsy specimens demonstrated varying quantities of epidermal melanin and residual epidermal melanocytes. Mild perivascular inflammation was evident in two specimens. Superficial dermal fibrosis was noted in all biopsy specimens. Topical photochemotherapy induced moderate to excellent repigmentation in 71% of the treated patients. Adverse effects were minimal. CONCLUSION: The results of this investigation suggest that hypopigmentation induced by laser resurfacing may result from a suppression of melanogenesis rather than destruction of area melanocytes. The preliminary data further suggest that hypopigmentation caused by laser resurfacing can be effectively treated by topical photochemotherapy.

Tumor of the follicular infundibulum with sebaceous differentiation.

BACKGROUND: Tumor of the follicular infundibulum (TFI) is a relatively rare tumor which clinically presents as a solitary keratotic papule usually on the head and neck which on microscopic examination typically reveals a plate-like fenestrated epithelial tumor composed of pale staining cells. METHODS: We describe a new variant of TFI. An 80-year-old male with a history of multiple basal cell carcinomas and a squamous cell carcinoma presented with a 2-year history of a red, scaly, slightly elevated plaque on the lateral aspect of his right buttock. RESULTS: Histopathological examination revealed plate-like reticulate epithelial outgrowths of large and pale cells with foci of sebaceous differentiation and numerous colloid bodies. Differential diagnosis included superficial basal cell carcinoma with sebaceous and ductal differentiation, tumor of the follicular infundibulum, an unusual fibroepithelioma of Pinkus or an eccrine fibroadenoma with sebaceous differentiation. CONCLUSION: This case illustrates a hybrid adnexal tumor with histologic features common to both tumor of the follicular infundibulum and superficial epithelioma with sebaceous differentiation.

An unusual melanocytic lesion associated with eccrine duct fibroadenomatosis and syringoid features.

The intimate association of nevomelanocytic nevi with eccrine ducts commonly seen in congenital nevi was emphasized by Mishima, who described as eccrine-centered nevi those lesions characterized by nevomelanocytic cells predominantly proliferating around and within the eccrine sweat duct walls. However, there were no changes in the overlying epidermis, dermis, or eccrine acrosyringeal or dermal duct proliferation in these lesions. We present the case of a 16-year-old boy with a 1-year-history of a 0.6-cm diameter single tan papule on the right heel, clinically thought to be a Spitz nevus. Histopathologic examination revealed a compound nevomelanocytic nevus associated with epidermal hyperplasia, thin anastomosing cords of acrosyringeal epithelium extending within the dermis, and eccrine ductal proliferation in a syringoma-like pattern associated with a dense fibrous stroma. Features that distinguish our case from eccrine-centered nevus are that the latter lacks epidermal and eccrine duct hyperplasia and a dense fibrous stroma. The location of the lesion on the heel in our case suggests the possibility that the pathologic changes observed could result from repetitive trauma.

Nephrogenic fibrosing dermopathy.

This report details the histopathologic findings in a unique fibrosing disorder that recently emerged among patients with renal disease. The affected patients were initially identified among recipients of renal transplants at a single institution, but later cases at other centers were identified, and included patients receiving renal dialysis for a variety of different kidney diseases. The cutaneous changes consisted largely of indurated plaques and papules on the extremities and trunk. Systemic findings seen in scleromyxedema, which the condition resembles in some respects, were absent. By routine microscopy, the findings range from a very subtle proliferation of dermal fibroblasts in early lesions, to a florid proliferation of fibroblasts and dendritic cells in fully developed cases. Thick collagen bundles with surrounding clefts are a prominent finding, and a variable increase in dermal mucin and elastic fibers was usually evident with special stains. CD-34 positive dermal dendrocytes were floridly abundant, with dendritic processes aligned with elastic fibers and around collagen bundles in a dense network. Factor XIIIa and CD-68 positive mono-and multinucleated cells are also present in increased numbers. Electron microscopy highlighted increased elastic fibers closely apposed to dendritic cell processes. The entire dermis was commonly involved, with increased spindle cells, collagen, mucin, and elastic fibers extending through the subcutis along the septa of fatty lobules. In some instances, the process resembled a sarcoma on histopathologic examination. The recent emergence of this condition and the apparent clustering of cases in specific dialysis centers initially suggested a possible infectious and/or toxic agent. To date, however, no such agent has been identified. We propose the term "nephrogenic fibrosing dermopathy (NFD)" until a specific cause can be identified.