Trisomy 8 in myeloid leukemia cutis confirmed by fluorescence in situ hybridization analysis

We present a case of a 64‐year‐old man with refractory acute myeloid leukemia and trisomy 8 who developed leukemia cutis. Interphase fluorescence in situ hybridization (FISH) was performed on a paraffin‐embedded skin section. FISH confirmed a population of cells with trisomy 8 in the blastic infiltrates involving the skin. This case illustrates a novel application of interphase FISH to confirm the diagnosis of leukemia cutis.     

动脉瘤样纤维组织细胞瘤一例

患者,女,71岁。左胫前黑褐色结节5年。结合临床症状和组织病理检查,诊断为动脉瘤样纤维组织细胞瘤。给予手术完整切除治疗,随访至今未复发。     

Diagnosis of blue nevus-like metastatic uveal melanoma confirmed by fluorescence in situ hybridization (FISH) for monosomy 3

Metastatic melanoma can on rare occasion simulate the appearance of a blue nevus clinically and/or histopathologically, which may lead to diagnostic confusion and delay in treatment. Given the known difficulty in recognizing a small dermal blue nevus-like melanoma metastasis by light microscopic findings alone, recent discoveries of unique cytogenetic aberrations in various types of melanomas have led pathologists to explore cytogenetic techniques as an ancillary diagnostic tool. Herein, we report a case of a 58-year-old man with a history of uveal melanoma, in which fluorescence in situ hybridization (FISH) analysis for monosomy 3 helped confirm a diagnosis of blue nevus-like uveal melanoma metastasis. The patient had presented clinically with a new small 1-mm dark blue-gray macule on the forehead. Histopathologically, a small dermal nodule of pigmented epithelioid melanocytes and melanophages was found with a rare mitotic figure. The pathologist's suspicion of a blue nevus-like melanoma metastasis was confirmed by FISH analysis: both the tumor cells of the patient's prior uveal melanoma and the melanocytes of the new dermal blue nevus-like nodule carried only one copy of chromosome 3. Furthermore, deletion of 1p36 and amplifications of 8q32 were also identified.     

A case of adult T-cell leukaemia/lymphoma characterized by multiplex-fluorescence in situ hybridization, comparative genomic hybridization, fluorescence in situ hybridization and cytogenetics

Adult T-cell leukaemia/lymphoma (ATLL) is a neoplasm of mature helper (CD4) T lymphocytes. Little is known, however, about the chromosome aberrations associated with the pathogenesis of this malignancy. Using molecular cytogenetic techniques we, therefore, investigated a 44-year-old man who had a 7-year history of ATLL with cutaneous involvement mimicking primary cutaneous T-cell lymphoma. Conventional cytogenetics revealed gross chromosomal changes with chromosome numbers ranging from 71 to 82. There were structural abnormalities of chromosomes 7 and 9, partial deletions of chromosomes 1, 3, 5 and 6, and loss of chromosomes 2, 4, 9, 11–14, 21 and 22. Multiplex-fluorescence in situ hybridization (M-FISH) identified two derivative chromosomes, der(6)t(6;7)(q16;q21) and der(7)t(6;7)(q16;q21)ins(6;12)(q2?;?), and a deletion of chromosome 1p. Conventional FISH confirmed the M-FISH findings. Comparative genomic hybridization of the blood revealed gains of DNA copy number at 1q12–25, 6p24–25, 9p23, 16p13–q13, 17q11–21, 19p13 and 20q13 and loss at 11p15 while lymph nodes showed gains at 3p22–24, 3q27–29, 7q36 and 15q26 and losses at 2p24–25, 2q37, 10p14–15, 11p15, 13q33–34 and 16p13.3. No DNA copy number changes were seen in a skin lesion. These results show the extent of genetic abnormalities within this malignancy.     

Benign fibrous histiocytoma of the foot: a literature review and case report

A rare case of benign fibrous histiocytoma involving the foot of a sixty-three-year-old white man is presented, with a review of the literature. The histopathologic appearance of benign fibrous histiocytoma, differential diagnosis, and surgical management are discussed. Fibrous histiocytomas are characteristically nonencapsulated tumors composed of a mixture of fibroblastic and histiocytic cells arranged in a storiform or cartwheel pattern.     

Incontinentia pigmenti in a boy with XXY mosaicism detected by fluorescence in situ hybridization

We report the case of a male infant with incontinentia pigmenti (MIM 308310) and low-grade XXY mosaicism. Fluorescence in situ hybridization may reveal the underlying genetic alteration in male patients with incontinentia pigmenti and a normal karyotype.     

Distinction of conjunctival melanocytic nevi from melanomas by fluorescence in situ hybridization

A conjunctival melanocytic nevus may on occasion be difficult to distinguish from melanoma both clinically and histopathologically. An unambiguous correct diagnosis is critical because of major differences in management and prognosis. We evaluated a fluorescence in situ hybridization (FISH) assay, which has previously been shown to be of value for the diagnosis of melanocytic nevi and melanomas of the skin, using probes targeting 6p25 (RREB1), 6q23 (MYB), 11q13 (CCND1) and centromere 6 (CEP6), for its potential to assist in the distinction of conjunctival melanocytic nevi from melanomas. Four melanocytic nevi and eight melanomas of the conjunctiva were analyzed. Two of the melanomas were diagnostically problematic because of suboptimal histopathology. None of the conjunctival melanocytic nevi showed a level of chromosomal aberrations that met FISH criteria for a diagnosis of melanoma. All eight conjunctival melanomas (six unequivocal and two suspicious lesions) met FISH criteria for melanoma. Thus, results from FISH assay targeting 6p25, 6q23, 11q13 and centromere 6 correlated well with the histopathologic diagnoses and supported the histopathologic suspicion in two problem cases. The findings encourage further exploration of this technique as an ancillary method for the work‐up of conjunctival melanocytic proliferations. Busam KJ, Fang Y, Jhanwar SC, Pulitzer MP, Marr B, Abramson DH. Distinction of conjunctival melanocytic nevi from melanomas by fluorescence in situ hybridization.     

EMA positivity in epithelioid fibrous histiocytoma: a potential diagnostic pitfall

Background: Epithelioid fibrous histiocytoma (EFH) represents a morphologic variant of cutaneous fibrous histiocytoma (FH) but can lack many characteristic features. The presence of epithelioid cytomorphology may mimic other dermal neoplasms. Our anecdotal experience of epithelial membrane antigen (EMA) expression in some examples of EFH has caused diagnostic difficulty. Our aim was to examine the immunohistochemical profile and incidence of EMA expression in EFH. Methods: Forty‐four cases of EFH were retrieved from consultation files. Clinicopathologic and immunohistochemical features were evaluated. Results: Membranous EMA positivity was found in tumor cells in 27/42 cases (64%). Focal positivity for factor XIIIa was found in 10/14 (71%) and D2‐40 in 14/27 (52%). Scattered smooth muscle actin (SMA)‐positive tumor cells were seen in 11/43 (25%). Focal positivity for claudin‐1 was found in 3/42 (7%). CD163 staining highlighted stromal macrophages; however, in five cases it was difficult to exclude focal staining of tumor cells. Tumor cells were consistently negative for pan‐keratin, AE1/AE3, S100, CD31, CD34, CD68, desmin, p63, GFAP and CD45/LCA. Conclusion: Frequent EMA expression in EFH represents an unexpected finding and constitutes a potential diagnostic pitfall. Although of uncertain significance, this finding, when combined with established morphologic differences, raises the possibility that EFH is unrelated to classic FH. Doyle LA, Fletcher CDM. EMA positivity in epithelioid fibrous histiocytoma: a potential diagnostic pitfall.     

An automatic analysis method for in situ hybridization using high-resolution image analysis

Summary Specific mRNA for ₁ (I) collagen has been detected on a cellular level by in situ hybridization using radioactively labelled ₁ (I) antisense RNA probes. We here present an automatic, quantitative, evaluation technique for the determination of grain densities using the high-resolution image analysis system IPS KONTRON. The reliability and objectivity of this method were evaluated by comparing the values of grains per cell obtained by conventional and automatic techniques following in situ hybridization with ₁ (I) collagen DNA probes in various specimens.The correlation coefficients between conventional and automatic analysis of grain densities were 0.97 for fibroblasts embedded into a three-dimensional collagen gel, 0.94 for dermal fibroblasts in skin obtained from a patient with progressive systemic scleroderma, and 0.90 for fibroblasts in a 2-week-old scar. All correlation coefficients were significant on the P<0.0001 level. This new analysis technique therefore allows a more rapid and reliable quantitative evaluation of in situ hybridization and may also be helpful in differentiating between various cell populations characterized by different biosynthetic capacities.This work was presented in part at the 15th Annual Meeting of the German Society for Dermatological Research, Munich, November 13–15, 1987. Supported by the Deutsche Forschungsgemeinschaft (grants Sto 189/1-1, Sch 411-1, and Kr 558/4-5) and the Friedrich-Baur-Foundation, Munich     

荧光原位杂交法观察小鼠皮肤组织切片中型无绿藻感染的研究

目的 探讨荧光原位杂交技术用于诊断小鼠皮肤中型无绿藻感染模型的可行性。 方法 制作小鼠皮肤中型无绿藻感染模型,制备皮肤组织石蜡切片,用人工合成的探针PZ-probe进行荧光原位杂交检测,以过碘酸锡夫（PAS）染色、HE染色做阳性对照;取正常及其他真菌感染的皮肤组织石蜡切片做阴性对照,以同样的方法进行荧光原位杂交检测,将各种检测方法的结果进行对比分析。 结果 小鼠临床体征、病理检测及病原体培养结果均证实皮肤无绿藻感染模型建立成功。通过荧光原位杂交法成功检测出了小鼠皮肤中型无绿藻感染模型皮肤组织中的无绿藻病原体,结果与PAS染色和HE染色一致;而在正常及其他真菌感染的皮肤组织石蜡切片中均未能检测出无绿藻。 结论 荧光原位杂交法可以检测出小鼠皮肤中型无绿藻感染模型组织石蜡切片中的无绿藻病原体。     

手术切除加125I植入治疗腹壁恶性纤维组织细胞瘤一例

患者男,72岁。因脐左侧结节3年,增大半年,于2013年6月来我科就诊。3年前发现脐左侧一蚕豆大皮色结节,无痛痒,近半年迅速增大,高出皮面,呈暗紫色,表面呈分叶状,无明显自觉症状,无发热、咳嗽、胸闷、乏力和消瘦等不适……     

FUS (16p11) gene rearrangement as detected by fluorescence in-situ hybridization in cutaneous low-grade fibromyxoid sarcoma: a potential diagnostic tool

Low-grade fibromyxoid sarcoma (LGFMS) is a rare, typically deep-seated soft tissue neoplasm with deceptively bland cytology and metastatic potential. A t(7;16)(q34;p11) translocation, yielding a FUS/CREB3L2 fusion gene, has been identified in approximately 80%-90% of deep soft tissue LGFMS. Cutaneous fibromyxoid neoplasms occur not infrequently; dermatopathologists rarely consider LGFMS in the differential diagnosis, as this lesion is uncommon in the skin. We identified a group of superficial LGFMS and a spectrum of other cutaneous fibromyxoid neoplasms and performed fluorescence in situ hybridization (FISH) to assess the frequency of FUS rearrangement. FISH for the chromosomal rearrangement of FUS (16p11), using a dual-color, break-apart probe (Abbott Molecular/Vysis, Des Plaines, IL), was performed on formalin-fixed paraffin-embedded tissue sections from superficial LGFMS (n = 6), myxomas (n = 10), and myxofibrosarcoma/myxoid malignant fibrous histiocytomas (myxoid MFH) (n = 5). One hundred nonoverlapping tumor nuclei per case were evaluated for either fused (normal) or split (translocated) signals. Of the LGFMS, 4 of 6 (67%) showed a rearrangement of FUS (range: 72%-80% positive nuclei per 100 nuclei). The other neoplasms within the differential diagnosis were devoid of any rearrangement involving FUS (range: 0%-2% positive nuclei per 100 nuclei). Our observed frequency of FUS rearrangement in superficial LGFMS is consistent with those published in the literature for more deeply seated lesions. When applied to suspicious superficial myxoid or fibromyxoid neoplasms, the FUS FISH probe in formalin-fixed paraffin-embedded tissue can be a useful ancillary technique for diagnosis of this uncommon and deceptively bland tumor.     

Desmin and CD34 positivity in cellular fibrous histiocytoma: an immunohistochemical analysis of 100 cases

Background: Cellular benign fibrous histiocytoma (CBFH) represents a morphologic variant of cutaneous fibrous histiocytoma (FH). Because of its relative monomorphism and frequent fascicularity, CBFH can easily be mistaken for a malignancy. In fact, CD34, often used to distinguish CBFH from dermatofibrosarcoma protuberans (DFSP), can also be positive. To add to the confusion, desmin positivity may also be observed in a subset of CBFH. Desmin and CD34 expression often cause interpretative difficulty which may lead to misdiagnosis. Our aim was to examine the incidence of desmin and CD34 expression in CBFH. Methods: One hundred consecutive cases of morphologically typical CBFH were retrieved from consultation files. Clinicopathologic and immunohistochemical features were evaluated. Results: SMA positivity was found in tumor cells in 93 of 100 cases (93%). Desmin positivity was found in 32 of 100 cases (32%). CD34 was positive in 6 of 100 cases (6%). There was no evident correlation between immunophenotype and anatomic site or other clinical variables. Conclusion: Frequent desmin (32%) and occasional CD34 (6%) expression are encountered in CBFH. Desmin positivity can be explained on the basis of myofibroblastic differentiation. The occasional CD34 positivity in a subset of CBFH should not be a deterrent from making the correct pathologic diagnosis, based on characteristic morphologic features.     

Postirradiation malignant fibrous histiocytoma. A case report with a review of postirradiation sarcoma in the Japanese literature

A fatal case of postirradiation malignant fibrous histiocytoma was reported, with a review of postirradiation sarcoma in the Japanese literature.     

Metastatic hidradenocarcinoma with demonstration of Her-2/neu gene amplification by fluorescence in situ hybridization: potential treatment implications

A 44-year-old man was referred for a right chest nodule of 3 months duration. A 'benign' nodule had been excised from this location 8 years prior. On examination, palpable nodes were noted in the right axilla. Radiographic studies were significant only for right axillary lymphadenopathy. Histologically, a nodular dermal proliferation composed of poorly differentiated epithelioid cells in nests and focally forming ducts with pseudopapillary architecture comprised the primary tumor. Features of a clear cell hidradenoma were noted focally. Immunohistochemical (IHC) analysis revealed reactivity for HMW cytokeratins, CK5 and CK7, p53, p63, CEA (focal), androgen receptor, EGFR, estrogen receptor (ER), MUC5AC, and strong/diffuse membranous staining for Her-2/neu. Negative stains included villin, TTF-1, CDX2, S-100 protein, vimentin, gross cystic disease fluid protein 15 (GCDFP-15), mammoglobulin, and MUC2. A wide local excision and axillary node dissection was performed. Metastatic tumor involved nine of 28 nodes. Interphase fluorescence in situ hybridization (FISH) demonstrated chromosomal amplification of the Her-2/neu locus within the tumor and a nodal metastasis. The patient has completed adjuvant and radiotherapy, including trastuzumab, and is asymptomatic. We believe this to be the first demonstration of Her-2/neu amplification in a malignant skin adnexal tumor. In analogy to breast carcinoma, these findings suggest the applicability of trastuzumab for patients with metastatic adnexal carcinomas demonstrating Her-2/neu amplification.     

Application of COL1A1–PDGFB fusion gene detection by fluorescence in situ hybridization in biopsy tissue of dermatofibrosarcoma protuberans

Several uncommon variants of dermatofibrosarcoma protuberans (DFSP) and the limitations of small biopsies render pathological diagnosis difficult. The aim of this study was to analyze the utility of fluorescence in situ hybridization (FISH) in the detection of the collagen type I‐α1/platelet derived growth factor‐β (COL1A1–PDGFB) fusion gene in biopsies of DFSP. Twenty‐three consecutive biopsy specimens of DFSP were reviewed for clinicopathological features and examined with the COL1A1–PDGFB fusion probe and PDGFB break‐apart probe using FISH analysis. The 23 tumor samples consisted of 11 males and 12 females (mean age at diagnosis, 37 years; range, 14–75 years). Eighteen conventional DFSP, one Bednar tumor, two myxoid DFSP and two fibrosarcomatous DFSP samples were included in the group. Strong and extensive CD34 expression was observed in 19 of 23 cases (83%). Twenty‐one cases (91%) were positive for both the COL1A1–PDGFB fusion signal and the PDGFB break‐apart signal. This is one of the few studies to demonstrate the value of FISH analysis of the COL1A1–PDGFB gene, which could validate complicated and suspected diagnoses in the routine biopsy of DFSP.