The histopathological diagnosis of melanoma is fraught with potential pitfalls. In the setting of cutaneous metastatic melanoma, it is important to recognise the various histological patterns that ...can be encountered from the more common to the rare, including epidermotropic, folliculotropic, naevoid, and blue naevus-like. In addition, melanoma is notorious for phenotypic plasticity. Thus, there are many different subtypes and cytomorphological variations that can be difficult to recognise as melanoma, particularly in the recurrent or metastatic setting. Select melanoma variants including primary dermal, clear cell, plasmacytoid, signet ring cell, small cell, myxoid, rhabdoid, and dedifferentiated melanoma will be discussed, in addition to composite melanocytic neoplasms. This review is intended to remind the practitioner of key concepts of metastatic disease and select rare melanoma variants, while providing practical guidelines for accurate diagnosis.
Atypical Spitz Tumors: A Diagnostic Challenge Harms, Kelly L; Lowe, Lori; Fullen, Douglas R ...
Archives of pathology & laboratory medicine (1976)
139, Številka:
10
Journal Article
Recenzirano
Odprti dostop
Spitzoid melanocytic lesions encompass a spectrum from benign Spitz nevi to malignant spitzoid melanomas. Spitzoid melanocytic neoplasms have significant morphologic and molecular differences from ...conventional melanocytic lesions, and prediction of biologic behavior and metastatic risk may be difficult. Most challenging is the atypical Spitz tumor, a borderline spitzoid melanocytic lesion of uncertain malignant potential that has overlapping histologic features with conventional Spitz nevus and spitzoid melanoma. Atypical Spitz tumors involve the sentinel lymph nodes at a greater frequency than conventional melanoma and frequently harbor chromosomal copy number changes, yet most cases follow an indolent course. Herein we review the clinical, microscopic, and molecular features of atypical Spitz tumors, including recent molecular advances, including the potential prognostic significance of chromosomal abnormalities, such as homozygous CDKN2A loss.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, OILJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK, VSZLJ
Cutaneous lupus erythematosus (CLE) is a chronic inflammatory skin disease characterized by a diverse cadre of clinical presentations. CLE commonly occurs in patients with systemic lupus ...erythematosus (SLE), and CLE can also develop in the absence of systemic disease. Although CLE is a complex and heterogeneous disease, several studies have identified common signaling pathways, including those of type I interferons (IFNs), that play a key role in driving cutaneous inflammation across all CLE subsets. However, discriminating factors that drive different phenotypes of skin lesions remain to be determined. Thus, we sought to understand the skin-associated cellular and transcriptional differences in CLE subsets and how the different types of cutaneous inflammation relate to the presence of systemic lupus disease. In this study, we utilized two distinct cohorts comprising a total of 150 CLE lesional biopsies to compare discoid lupus erythematosus (DLE), subacute cutaneous lupus erythematosus (SCLE), and acute cutaneous lupus erythematosus (ACLE) in patients with and without associated SLE. Using an unbiased approach, we demonstrated a CLE subtype-dependent gradient of B cell enrichment in the skin, with DLE lesions harboring a more dominant skin B cell transcriptional signature and enrichment of B cells on immunostaining compared to ACLE and SCLE. Additionally, we observed a significant increase in B cell signatures in the lesional skin from patients with isolated CLE compared with similar lesions from patients with systemic lupus. This trend was driven primarily by differences in the DLE subgroup. Our work thus shows that skin-associated B cell responses distinguish CLE subtypes in patients with and without associated SLE, suggesting that B cell function in skin may be an important link between cutaneous lupus and systemic disease activity.
Merkel cell carcinoma (MCC) is a relatively rare, potentially aggressive cutaneous malignancy. We examined the clinical and histologic features of primary MCC that may correlate with the probability ...of a positive sentinel lymph node (SLN).
Ninety-five patients with MCC who underwent SLN biopsy at the University of Michigan were identified. SLN biopsy was performed on 97 primary tumors, and an SLN was identified in 93 instances. These were reviewed for clinical and histologic features and associated SLN positivity. Univariate associations between these characteristics and a positive SLN were tested for by using either the χ(2) or the Fisher's exact test. A backward elimination algorithm was used to help create a best multiple variable model to explain a positive SLN.
SLN positivity was significantly associated with the clinical size of the lesion, greatest horizontal histologic dimension, tumor thickness, mitotic rate, and histologic growth pattern. Two competing multivariate models were generated to predict a positive SLN. The histologic growth pattern was present in both models and combined with either tumor thickness or mitotic rate.
Increasing clinical size, increasing tumor thickness, increasing mitotic rate, and infiltrative tumor growth pattern were significantly associated with a greater likelihood of a positive SLN. By using the growth pattern and tumor thickness model, no subgroup of patients was predicted to have a lower than 15% to 20% likelihood of a positive SLN. This suggests that all patients presenting with MCC without clinical evidence of regional lymph node disease should be considered for SLN biopsy.
Recent evidence suggests that alterations in the self-renewal program of stem/progenitor cells can cause tumorigenesis. By utilizing genetically engineered mouse models of neurofibromatosis type 1 ...(NF1), we demonstrated that plexiform neurofibroma, the only benign peripheral nerve sheath tumor with potential for malignant transformation, results from
Nf1 deficiency in fetal stem/progenitor cells of peripheral nerves. Surprisingly, this did not cause hyperproliferation or tumorigenesis in early postnatal period. Instead, peripheral nerve development appeared largely normal in the absence of
Nf1 except for abnormal Remak bundles, the nonmyelinated axon-Schwann cell unit, identified in postnatal mutant nerves. Subsequent degeneration of abnormal Remak bundles was accompanied by initial expansion of nonmyelinating Schwann cells. We suggest abnormally differentiated Remak bundles as a cell of origin for plexiform neurofibroma.
Melanocytic lesions with borderline features are diagnostically challenging. Single-nucleotide polymorphism (SNP) arrays, which detect genomic copy number alterations (CNAs), can be helpful in ...distinguishing between nevi and melanoma. Fluorescence in situ hybridization (FISH) has been used as a more rapid, less expensive alternative to SNP array, using a panel of probes that are often gained or lost in melanoma. We used SNP array data from 63 borderline cutaneous melanocytic lesions and 44 definitive melanomas to predict the performance of FISH testing. Lesions were considered positive by “virtual FISH” if 1 or more of the 5 FISH-probed loci demonstrated appropriate CNAs by SNP array. Cases were classified as positive by SNP array if ≥3 CNAs were present, based on internal validation studies, or if FISH criteria were met. Conventional FISH was performed in 33 cases (17 borderline lesions, 16 melanomas). Of the 63 borderline cases, 44 (70%) were positive by SNP array and 30 (48%) were positive by virtual FISH. A higher proportion of melanomas were positive by SNP array (41/44, 93% sensitivity) and virtual FISH (36/44, 82% sensitivity). Virtual FISH had 61% sensitivity in the borderline group using SNP array as the gold standard, whereas specificity was 84%. There was good correlation between conventional and virtual FISH, with agreement in 30 of 33 (91%) cases. Although FISH is highly effective in distinguishing between nevi and melanoma in cases where the histological diagnosis is straightforward, it is not nearly as sensitive or specific as SNP array when applied to borderline lesions.
•Molecular techniques can be helpful in distinguishing melanoma from nevi.•SNP array is more sensitive and specific than FISH in diagnosing borderline lesions.•“Virtual FISH” from SNP array data correlates closely with conventional FISH.
Background
Dermatofibrosarcoma protuberans (DFSP) is a rare dermal tumor with local recurrence rates ranging from 0 to 50%. Controversy exists regarding margin width and excision techniques, with ...some advocating Mohs surgery and others wide excision (WE). We reviewed the experience in two tertiary centers using WE with total peripheral margin pathologic evaluation.
Materials and Methods
Institutional Review Board approved retrospective review of patients with DFSP from 1991 to 2008. Patients had initial WE using 1–2 cm margins with primary or delayed closure; further excision was done whenever feasible for positive margins. Pathologic analysis included en face sectioning. We evaluated margin width, number of WE, reconstruction methods, radiation, and outcomes.
Results
A total of 206 DFSP lesions in 204 patients (76 males, 128 females), median age 41 years (range 1–84) were treated. Locations were trunk (135), extremities (43), and head and neck (28). The median number of excisions to achieve negative margins was 1 (range 1–4) with a median excision width of 2 cm (range 0.5–3 cm). Closure techniques included primary closure (142; 69%), skin grafting (52; 25%), and tissue flaps (9; 4%). There were 9 patients who received postoperative radiation, 6 for positive margins after maximal surgical excision. At a median follow-up of 64 months (range 1–210), 2 patients (1%) with head and neck primaries recurred locally.
Conclusions
Using a standardized surgical approach including meticulous pathologic evaluation of margins, a very low recurrence rate (1%) was achieved with relatively narrow margins (median 2 cm), allowing primary closure in 69% of patients. This approach spares the additional morbidity associated with wider resection margins and in our experience represents the treatment of choice for DFSP occurring on the trunk and extremities.
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