Linglei Ma | University of Michigan (original) (raw)

Papers by Linglei Ma

Research paper thumbnail of Keratin Filament Suspensions Show Unique Micromechanical Properties

this article were defrayed in part by the payment of page charges. This article must therefore be... more this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Research paper thumbnail of Pathologic quiz case: a 55-year-old woman with an adrenal mass

Archives of pathology & laboratory medicine

Research paper thumbnail of The expression of MUM1 in cutaneous T-cell lymphoproliferative disorders

Human pathology, 2008

MUM1 is a member of the interferon regulatory factor family of transcription factors. It is norma... more MUM1 is a member of the interferon regulatory factor family of transcription factors. It is normally expressed in plasma cells, late B cells, and activated T cells, and has been described in several B-cell malignancies. Although its expression has been reported in some T-cell neoplasms, the full range and character of expression have not been explored. We studied 58 cases of T-cell lymphoproliferative lesions, including systemic and cutaneous anaplastic large cell lymphoma, lymphomatoid papulosis (LyP), mycosis fungoides (MF), MF with large cell transformation, and Sézary syndrome (SS). Nearly all cutaneous (5/5) and systemic anaplastic large cell lymphomas (4/5) were positive for MUM1, mainly in the large cell population. Similarly, 12 of 16 types A and C LyP showed MUM1 reactivity in greater than 50% of the large cells. Focal MUM1 staining was seen in 3 type B LyP, mostly in reactive lymphoid cells. All 9 MF with large cell transformation expressed MUM1 in large cells, where it pa...

Research paper thumbnail of Expression of gamma-H2AX in melanocytic lesions

Human pathology, 2008

gamma-H2AX is a marker of activated DNA damage and is overexpressed in many malignancies and thei... more gamma-H2AX is a marker of activated DNA damage and is overexpressed in many malignancies and their precursor lesions. Previous studies have demonstrated the expression of gamma-H2AX in melanoma and dysplastic nevus, but its diagnostic and prognostic utility in a full range of melanocytic lesions has not been fully studied. In the current study, we investigated gamma-H2AX expression in a total of 162 melanocytic lesions. We found that gamma-H2AX was observed at higher levels (percentage and intensity of staining) in melanoma in situ (12/13), primary cutaneous melanoma (32/33; with the exception of desmoplastic melanoma), and metastatic melanoma (58/62), which was statistically different from that in benign nevus (7/9), dysplastic nevus (6/10), and Spitz nevus (5/9) considered together (P < .0001). Of note, desmoplastic melanoma (20/26) demonstrated weak or negative gamma-H2AX staining. The expression of gamma-H2AX did not show significant correlation with many melanoma prognostic ...

Research paper thumbnail of Atypical angiomyolipoma of kidney in a patient with tuberous sclerosis: a case report with p53 gene mutation analysis

Archives of pathology & laboratory medicine, 2005

Angiomyolipoma (AML) is the most common benign mesenchymal tumor of the kidney. It belongs to the... more Angiomyolipoma (AML) is the most common benign mesenchymal tumor of the kidney. It belongs to the family of perivascular epithelioid cell tumors and is typically composed of blood vessels, adipose tissue, and smooth muscle- like cells, which are characteristically positive for HMB-45. Results of recent studies suggest that p53 mutation may play an important role in AML progression. Here, we describe a locally destructive renal AML in a patient with tuberous sclerosis. The tumor consisted of mostly epithelioid cells with marked nuclear pleomorphism and frequent mitoses and was positive for HMB-45. The diagnosis of atypical epithelioid AML was made. Codon alteration in the p53 gene was not detected, despite focal p53 immunoreactivity and single nucleotide polymorphism at exon 6. Our finding indicates no definite link between p53 abnormalities and the atypical appearance of AML. To the best of our knowledge, this is the second renal AML case investigated for p53 mutations.

Research paper thumbnail of Primary localized laryngeal amyloidosis: report of 3 cases with long-term follow-up and review of the literature

Archives of pathology & laboratory medicine, 2005

Localized laryngeal amyloidosis is an uncommon condition with limited long-term follow-up studies... more Localized laryngeal amyloidosis is an uncommon condition with limited long-term follow-up studies. The precise etiology and pathogenesis are not entirely clear. To further characterize the histopathologic features and possible pathogenesis of localized laryngeal amyloidosis. Three cases of primary localized laryngeal amyloidosis were identified at our institutions from 1980 to 2003. The clinical features and histologic and immunohistochemical patterns were evaluated. Systemic workups were pursued during the long-term follow-up. The common presentation of the patients was hoarseness. The lesions involved vocal cords, anterior commissure, and ventricle. Microscopically, the amyloid was present within the submucosa with an adjacent lymphoplasmacytic infiltrate. The plasma cells and amyloid demonstrated monoclonal light chain restriction in all 3 cases (2 lambda, 1 kappa). No evidence of systemic amyloidosis or an overt B-cell lymphoma was found in these patients. Two patients with long...

Research paper thumbnail of Correction: Perivascular epithelioid cell tumor (PEComa) of the uterine cervix associated with intraabdominal "PEComatosis": A clinicopathological study with comparative genomic hybridization analysis

World journal of surgical oncology, Jan 3, 2005

Research paper thumbnail of Cutaneous basal cell carcinosarcomas: evidence of clonality and recurrent chromosomal losses

Human Pathology, 2015

Human Pathology (2015) xx, xxx-xxx additional changes including recurrent 9p21 losses and a relat... more Human Pathology (2015) xx, xxx-xxx additional changes including recurrent 9p21 losses and a relatively high burden of copy number changes. In addition, most cutaneous carcinosarcomas show evidence of clonality between epithelial and mesenchymal components. Published by Elsevier Inc.

Research paper thumbnail of From Melanocyte to Metastatic Malignant Melanoma

Dermatology Research and Practice, 2010

Malignant melanoma is one of the most aggressive malignancies in human and is responsible for alm... more Malignant melanoma is one of the most aggressive malignancies in human and is responsible for almost 60% of lethal skin tumors. Its incidence has been increasing in white population in the past two decades. There is a complex interaction of environmental (exogenous) and endogenous, including genetic, risk factors in developing malignant melanoma. 8-12% of familial melanomas occur in a familial setting related to mutation of the CDKN2A gene that encodes p16. The aim of this is to briefly review the microanatomy and physiology of the melanocytes, epidemiology, risk factors, clinical presentation, historical classification and histopathology and, more in details, the most recent discoveries in biology and genetics of malignant melanoma. At the end, the final version of 2009 AJCC malignant melanoma staging and classification is presented. of Hindawi Publishing Corporation

Research paper thumbnail of DEK expression in melanocytic lesions

Human pathology, 2011

The diagnosis of malignant melanoma presents a clinical challenge and relies principally on histo... more The diagnosis of malignant melanoma presents a clinical challenge and relies principally on histopathological evaluation. Previous studies have indicated that increased expression of the DEK oncogene, a chromatin-bound factor, could contribute to the development of melanoma and may be a frequent event in melanoma progression. Here, we investigated DEK expression by immunohistochemistry in a total of 147 melanocytic lesions, including ordinary nevi, dysplastic nevi, Spitz nevi, melanoma in situ, primary invasive melanomas, and metastatic melanomas. Most benign nevi (ordinary, dysplastic, and Spitz nevi) were negative or exhibited weak staining for DEK, with only 4 of 49 cases showing strong staining. Similar to benign nevi, melanoma in situ also demonstrated low levels of DEK expression. In contrast, the expression of DEK in primary invasive melanomas was significantly higher than benign nevi (P < .0001). Moreover, DEK expression was significantly increased in deep melanomas (Bres...

Research paper thumbnail of Expression of the embryonic morphogen Nodal in cutaneous melanocytic lesions

Modern Pathology, 2010

Nodal, a potent embryonic morphogen in the transforming growth factor-b family, is a proposed key... more Nodal, a potent embryonic morphogen in the transforming growth factor-b family, is a proposed key regulator of melanoma tumorigenicity. However, there has been no systematic study of Nodal expression in melanocytic lesions. We investigated Nodal expression by immunohistochemistry in 269 melanocytic lesions, including compound nevi, dysplastic nevi, congenital nevi, Spitz nevi, melanoma in situ, malignant melanoma including the variant desmoplastic melanoma, and metastatic melanoma. We found that the Nodal expression was significantly increased in malignant lesions (including melanoma in situ, malignant melanoma, and metastatic melanoma) compared with compound nevi, Spitz nevi, and dysplastic nevi. Surprisingly, congenital nevi expressed a level of Nodal comparable with malignant lesions, whereas desmoplastic melanoma showed lower expression than nondesmoplastic malignant melanoma (Po0.05). Deep melanoma (Breslow depth 41 mm) displayed a higher percentage of Nodal-positive tumor cells than did superficial melanoma (Breslow depth r1 mm), although there was no statistical difference in the overall staining intensity (P ¼ 0.18). Melanomas in situ showed a lower level of Nodal expression than did deep melanomas and metastatic melanomas (Po0.05). The low expression of Nodal in normal and dysplastic nevi, and its increasing expression with the progression of malignant lesions, are suggestive of a role for Nodal in melanoma progression.

Research paper thumbnail of Diagnostic utility of IMP3 in segregating metastatic melanoma from benign nevi in lymph nodes

Modern Pathology, 2009

Depending on the Breslow depth of the primary melanoma, sentinel lymph node biopsy is considered ... more Depending on the Breslow depth of the primary melanoma, sentinel lymph node biopsy is considered as standard of care for the staging of cutaneous melanoma, and is one of the most important prognostic factors. The histologic analysis of these specimens becomes difficult to interpret when benign intranodal nevic cells mimic metastases. Insulin-like growth factor-II messenger RNA (mRNA)-binding protein-3 (IMP3), also known as K homology domain-containing protein overexpressed in cancer or L523S, is a member of the insulin-like growth factor-II mRNA-binding protein family and has been shown to have diagnostic utility in distinguishing cutaneous melanoma from benign nevi. In this study, 43 sentinel lymph node biopsy specimens, including 13 with benign intranodal nevi and 30 with metastatic melanoma (two cases containing both benign nevi and metastatic melanoma), from 41 patients were immunohistochemically analyzed with a monoclonal antibody against IMP3. None of the benign intranodal nevi expressed IMP3, whereas 21 out of 30 (70%) of the lymph nodes containing metastatic melanoma did. It seems that IMP3 is helpful in distinguishing benign intranodal nevi from metastatic melanoma in sentinel lymph node biopsy specimens, and could be a valuable diagnostic adjunct in sentinel lymph node biopsy assessment in which questions arise as to the malignancy of the melanocytes present.

Research paper thumbnail of Cutaneous Richter syndrome: Report of 3 cases from one institution

Journal of the American Academy of Dermatology, 2012

Richter syndrome (RS) is large-cell transformation of chronic lymphocytic leukemia (CLL). It comm... more Richter syndrome (RS) is large-cell transformation of chronic lymphocytic leukemia (CLL). It commonly involves lymph nodes and bone marrow, but may rarely manifest in skin. Certain triggering factors, such as Epstein-Barr virus infection and p53 overexpression, have been implicated in the pathogenesis of RS. Here, we present 3 cases of cutaneous RS from our institution with a follow-up period of up to 8 years. We present a series of cutaneous RS from a single institution with the longest follow-up period (up to 8 years) to date. Clinical characteristics were collected and histopathological findings of skin biopsy specimens were analyzed. All 3 patients had prior CLL and later developed cutaneous RS lesions. The mean age at the diagnosis of cutaneous RS was 67 years old. The time intervals between CLL and cutaneous RS were 3 to 8 years. Skin biopsy specimens demonstrated dermal nodular or perivascular infiltrates of large B cells, showing similar immunophenotypes to the lesional cells in the original CLL. Overexpression of p53 and positive stain for Epstein-Barr virus--encoded small RNA was found in one patient. One patient remained alive 8 years after the diagnosis whereas the other two died of the disease at 5 years and 3 weeks, respectively, after the onset of cutaneous RS. Three patients with RS were followed up for up to 8 years. Our findings suggested that, in contrast to extracutaneous RS, cutaneous RS generally has a less aggressive course with longer survival unless other worse prognostic factors are present.

Research paper thumbnail of Continuing Medical Education Article Comparison of CD23 staining patterns in Merkel cell carcinoma and non-cutaneous small cell carcinoma

Background: During our daily practice, we observed that cluster designation 23 (CD23) (clone BU38... more Background: During our daily practice, we observed that cluster designation 23 (CD23) (clone BU38) labels Merkel cells in normal skin. In this study, we examined the expression of CD23 in Merkel cell carcinoma (MCC) and assessed its usefulness in distinguishing MCC from non-cutaneous small cell carcinoma (SMCC). Methods: Immunohistochemical staining of CD23 was performed on a total of 33 MCCs, 22 SMCCs and 5 carcinoid tumors. Results: CD23 reactivity was present in 32 of 33 (97%) MCCs, 18 of 22 (82%) SMCCs and 5 of 5 (100%) carcinoid tumors. In MCC, 19 cases (59%) showed a predominance of perinuclear dot-like staining similar to cytokeratin 20, 3 (9%) showed mostly cytoplasmic staining and 10 (31%) displayed a combination of perinuclear dot-like and cytoplasmic staining. In contrast, all CD23-positive SMCCs and carcinoid tumors showed a diffuse cytoplasmic staining. There was a significant difference in the CD23 staining patterns between MCC and SMCC (p , 0.0001). Conclusion: CD23 i...

Research paper thumbnail of CD163 expression in leukemia cutis

Journal of Cutaneous Pathology, 2010

Proper diagnosis of myeloid leukemia cutis (LC) is of great clinical importance but can be diffic... more Proper diagnosis of myeloid leukemia cutis (LC) is of great clinical importance but can be difficult because no single immunohistochemical marker is adequately sensitive or specific for definitive diagnosis. Thus, a broader panel of markers is often desirable. CD163 is highly specific for normal and neoplastic cells of the monocyte/histiocyte lineage. In this study, we examined the value of CD163 in the diagnosis of acute myeloid LC. A total of 34 cases, including 18 cases of myelomonocytic or monocytic LC, 10 cases of myeloid LC without monocytic component and 6 cases of acute lymphoblastic leukemia/lymphoma (ALL), were stained with CD163. CD163 was expressed in 8 of 18 (44%) of myelomonocytic or monocytic LC and 1 of 10 (10%) of other myeloid LC, but in none of the ALL cases (0/6). CD163 was highly specific (90%) for myeloid LC with a monocytic component, but showed low sensitivity in the diagnosis of both myeloid LC in general (24%) and myeloid LC with a monocytic component (44%). Our results suggest that CD163 has utility as a specific marker for myeloid LC in conjunction with currently used immunohistochemical stains, but should not be used alone for diagnosis.

Research paper thumbnail of Diagnostic value of CD163 in cutaneous spindle cell lesions

Journal of Cutaneous Pathology, 2009

Background: The histologic diagnosis of atypical fibroxanthoma (AFX) can sometimes be challenging... more Background: The histologic diagnosis of atypical fibroxanthoma (AFX) can sometimes be challenging. No specific marker exists to confirm the diagnosis other than excluding other entities. CD163 has been shown to have great specificity for tumors of monocyte/histiocyte lineage. In this study, we evaluated the diagnostic utility of CD163 in diagnosing AFX and in identifying skin lesions with histiocytic/ dendritic derivation. Methods: A total of 157 cases, including 14 AFXs, 5 spindle cell squamous cell carcinomas (SCCs), and 7 spindle cell/desmoplastic melanomas, along with other cutaneous spindle cell and histiocytic/ fibrohistiocytic lesions, were stained with CD163. Results: CD163 was expressed in 11 of 14 (79%) AFXs, with moderate to strong intensity. No staining was observed in cases of spindle cell SCC (0/5) and dermatofibrosarcoma protuberans (0/10). Rare spindle cell/desmoplastic melanomas (2/7) and cutaneous leiomyosarcomas (1/5) demonstrated positive staining. CD163 reactivity was seen in 24 of 29 of benign fibrous histiocytomas (BFHs), including 8 of 8 celular fibrous histiocytomas and 6 of 9 epithelioid cell histiocytomas. The majority of cutaneous histiocytic lesions, including juvenile xanthogranuloma, Langerhans cell histiocytosis and Rosai-Dorfman disease, were positive for CD163. Conclusion: CD163 is a useful adjunct in distinguishing AFX from other malignant cutaneous spindle cell tumors and offers improved specificity in identifying cutaneous histiocytic/dendritic lesions.

Research paper thumbnail of The expression of CD23 in cutaneous non-lymphoid neoplasms

Journal of Cutaneous Pathology, 2007

Research paper thumbnail of IMP-3 expression in melanocytic lesions

Journal of Cutaneous Pathology, 2010

Insulin-like growth factor-II mRNA-binding protein 3 (IMP-3 ), a member of the insulin-like growt... more Insulin-like growth factor-II mRNA-binding protein 3 (IMP-3 ), a member of the insulin-like growth factor mRNA-binding protein family, is expressed in several human malignancies, including melanomas. However, the expression of IMP-3 has not been explored in melanoma in situ, various histologic subtypes of invasive melanomas and atypical Spitz tumors. IMP-3 immunostain was performed in 157 melanocytic lesions. Nearly all benign (8/8), dysplastic (8/8) and Spitz nevi (8/9) were negative for IMP-3. Focal IMP-3 positivity was observed in 5/12 melanoma in situ and 4/15 superficial melanomas (Breslow depth &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;or=1 mm). Half (10/20) of deep melanomas (Breslow depth &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;1 mm) and 25/52 metastatic melanomas demonstrated strong IMP-3 staining. IMP-3 expression differs significantly between non-desmoplastic melanomas (superficial and deep) and benign or dysplastic or Spitz nevi (p = 0.0427, respectively). Four of 23 desmoplastic melanomas expressed IMP-3 , which was significantly different from deep melanomas (p = 0.0109). IMP-3 stained 7 of 10 atypical Spitz tumors. The difference between atypical Spitz tumors and Spitz nevi was statistically significant (p = 0.0256). A malignant circumstance, such as non-desmoplastic melanoma or atypical Spitz tumor, can be inferred when IMP-3 is expressed, suggesting potential diagnostic value of IMP-3 in melanocytic lesions.

Research paper thumbnail of Fatal Subcutaneous Panniculitis-Like T-Cell Lymphoma (Sptcl) with Interface Change and Dermal Mucin, A Dead-Ringer for Lupus Erythematosus

Journal of Cutaneous Pathology, 2008

ABSTRACT We report a 48-year-old man who presented with ulcerated plaques and nodules of the lowe... more ABSTRACT We report a 48-year-old man who presented with ulcerated plaques and nodules of the lower extremities. Skin biopsies revealed a dense lymphocytic infiltrate involving the dermis and the subcutis in a lobular and septal pattern. No overt cytological atypia was present. Notably, several features resembling lupus erythematosus were present, including vacuolar interface change and abundant dermal mucin deposition. The patient developed pulmonary nodules, and a lung biopsy showed a perivascular and interstitial lymphoid infiltrate without overt atypia. The cutaneous and pulmonary lymphoid infiltrates showed similar immunohistochemical profiles: CD3(+) CD4(-) CD8(+/-) CD56(+). Monoclonal rearrangements of the T-cell receptor gamma gene with similar migration patterns were identified from both locations. The patient developed fatal hemophagocytic syndrome, involving liver, spleen, lymph nodes, and bone marrow. This case is one amongst the rare reports of subcutaneous panniculitis-like T-cell lymphoma with systemic involvement.

Research paper thumbnail of Atypical fibroxanthoma with lymphomatoid reaction

Journal of Cutaneous Pathology, 2011

Atypical fibroxanthoma (AFX) represents an uncommon skin tumor typically occurring on sun-damaged... more Atypical fibroxanthoma (AFX) represents an uncommon skin tumor typically occurring on sun-damaged skin of the elderly. Histopathologic variants include spindled, clear cell, osteoid, osteoclastic, chondroid, pigmented, granular cell and myxoid lesions. To date, an atypical lymphoid infiltrate, including CD30-positive large cells mimicking lymphomatoid papulosis, has not been described in association with AFX. The clinical and histopathological characteristics of two AFX cases inciting an atypical lymphoid infiltrate, along with immunohistochemical profiles and T-cell receptor gamma (TCRγ) gene rearrangement results, were reviewed. Lesions in both cases occurred as solitary nodules in elderly patients. Microscopically, both lesions showed a cellular proliferation composed of pleomorphic spindle cells, associated with a prominent intralesional atypical lymphoid infiltrate. The spindle cells expressed CD10 but lacked the expression of S-100, cytokeratins and muscle markers, thereby confirming the diagnosis of AFX. CD30 highlighted a significant subset of large mononuclear cells in the lymphoid infiltrate of one case. TCRγ gene rearrangement analyses were negative for both cases. An atypical lymphoid infiltrate, including the one resembling lymphomatoid papulosis, associated with AFX has not been previously described. It is important to recognize the reactive nature of the infiltrate to avoid a misdiagnosis of lymphoma.

Research paper thumbnail of Keratin Filament Suspensions Show Unique Micromechanical Properties

this article were defrayed in part by the payment of page charges. This article must therefore be... more this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Research paper thumbnail of Pathologic quiz case: a 55-year-old woman with an adrenal mass

Archives of pathology & laboratory medicine

Research paper thumbnail of The expression of MUM1 in cutaneous T-cell lymphoproliferative disorders

Human pathology, 2008

MUM1 is a member of the interferon regulatory factor family of transcription factors. It is norma... more MUM1 is a member of the interferon regulatory factor family of transcription factors. It is normally expressed in plasma cells, late B cells, and activated T cells, and has been described in several B-cell malignancies. Although its expression has been reported in some T-cell neoplasms, the full range and character of expression have not been explored. We studied 58 cases of T-cell lymphoproliferative lesions, including systemic and cutaneous anaplastic large cell lymphoma, lymphomatoid papulosis (LyP), mycosis fungoides (MF), MF with large cell transformation, and Sézary syndrome (SS). Nearly all cutaneous (5/5) and systemic anaplastic large cell lymphomas (4/5) were positive for MUM1, mainly in the large cell population. Similarly, 12 of 16 types A and C LyP showed MUM1 reactivity in greater than 50% of the large cells. Focal MUM1 staining was seen in 3 type B LyP, mostly in reactive lymphoid cells. All 9 MF with large cell transformation expressed MUM1 in large cells, where it pa...

Research paper thumbnail of Expression of gamma-H2AX in melanocytic lesions

Human pathology, 2008

gamma-H2AX is a marker of activated DNA damage and is overexpressed in many malignancies and thei... more gamma-H2AX is a marker of activated DNA damage and is overexpressed in many malignancies and their precursor lesions. Previous studies have demonstrated the expression of gamma-H2AX in melanoma and dysplastic nevus, but its diagnostic and prognostic utility in a full range of melanocytic lesions has not been fully studied. In the current study, we investigated gamma-H2AX expression in a total of 162 melanocytic lesions. We found that gamma-H2AX was observed at higher levels (percentage and intensity of staining) in melanoma in situ (12/13), primary cutaneous melanoma (32/33; with the exception of desmoplastic melanoma), and metastatic melanoma (58/62), which was statistically different from that in benign nevus (7/9), dysplastic nevus (6/10), and Spitz nevus (5/9) considered together (P < .0001). Of note, desmoplastic melanoma (20/26) demonstrated weak or negative gamma-H2AX staining. The expression of gamma-H2AX did not show significant correlation with many melanoma prognostic ...

Research paper thumbnail of Atypical angiomyolipoma of kidney in a patient with tuberous sclerosis: a case report with p53 gene mutation analysis

Archives of pathology & laboratory medicine, 2005

Angiomyolipoma (AML) is the most common benign mesenchymal tumor of the kidney. It belongs to the... more Angiomyolipoma (AML) is the most common benign mesenchymal tumor of the kidney. It belongs to the family of perivascular epithelioid cell tumors and is typically composed of blood vessels, adipose tissue, and smooth muscle- like cells, which are characteristically positive for HMB-45. Results of recent studies suggest that p53 mutation may play an important role in AML progression. Here, we describe a locally destructive renal AML in a patient with tuberous sclerosis. The tumor consisted of mostly epithelioid cells with marked nuclear pleomorphism and frequent mitoses and was positive for HMB-45. The diagnosis of atypical epithelioid AML was made. Codon alteration in the p53 gene was not detected, despite focal p53 immunoreactivity and single nucleotide polymorphism at exon 6. Our finding indicates no definite link between p53 abnormalities and the atypical appearance of AML. To the best of our knowledge, this is the second renal AML case investigated for p53 mutations.

Research paper thumbnail of Primary localized laryngeal amyloidosis: report of 3 cases with long-term follow-up and review of the literature

Archives of pathology & laboratory medicine, 2005

Localized laryngeal amyloidosis is an uncommon condition with limited long-term follow-up studies... more Localized laryngeal amyloidosis is an uncommon condition with limited long-term follow-up studies. The precise etiology and pathogenesis are not entirely clear. To further characterize the histopathologic features and possible pathogenesis of localized laryngeal amyloidosis. Three cases of primary localized laryngeal amyloidosis were identified at our institutions from 1980 to 2003. The clinical features and histologic and immunohistochemical patterns were evaluated. Systemic workups were pursued during the long-term follow-up. The common presentation of the patients was hoarseness. The lesions involved vocal cords, anterior commissure, and ventricle. Microscopically, the amyloid was present within the submucosa with an adjacent lymphoplasmacytic infiltrate. The plasma cells and amyloid demonstrated monoclonal light chain restriction in all 3 cases (2 lambda, 1 kappa). No evidence of systemic amyloidosis or an overt B-cell lymphoma was found in these patients. Two patients with long...

Research paper thumbnail of Correction: Perivascular epithelioid cell tumor (PEComa) of the uterine cervix associated with intraabdominal "PEComatosis": A clinicopathological study with comparative genomic hybridization analysis

World journal of surgical oncology, Jan 3, 2005

Research paper thumbnail of Cutaneous basal cell carcinosarcomas: evidence of clonality and recurrent chromosomal losses

Human Pathology, 2015

Human Pathology (2015) xx, xxx-xxx additional changes including recurrent 9p21 losses and a relat... more Human Pathology (2015) xx, xxx-xxx additional changes including recurrent 9p21 losses and a relatively high burden of copy number changes. In addition, most cutaneous carcinosarcomas show evidence of clonality between epithelial and mesenchymal components. Published by Elsevier Inc.

Research paper thumbnail of From Melanocyte to Metastatic Malignant Melanoma

Dermatology Research and Practice, 2010

Malignant melanoma is one of the most aggressive malignancies in human and is responsible for alm... more Malignant melanoma is one of the most aggressive malignancies in human and is responsible for almost 60% of lethal skin tumors. Its incidence has been increasing in white population in the past two decades. There is a complex interaction of environmental (exogenous) and endogenous, including genetic, risk factors in developing malignant melanoma. 8-12% of familial melanomas occur in a familial setting related to mutation of the CDKN2A gene that encodes p16. The aim of this is to briefly review the microanatomy and physiology of the melanocytes, epidemiology, risk factors, clinical presentation, historical classification and histopathology and, more in details, the most recent discoveries in biology and genetics of malignant melanoma. At the end, the final version of 2009 AJCC malignant melanoma staging and classification is presented. of Hindawi Publishing Corporation

Research paper thumbnail of DEK expression in melanocytic lesions

Human pathology, 2011

The diagnosis of malignant melanoma presents a clinical challenge and relies principally on histo... more The diagnosis of malignant melanoma presents a clinical challenge and relies principally on histopathological evaluation. Previous studies have indicated that increased expression of the DEK oncogene, a chromatin-bound factor, could contribute to the development of melanoma and may be a frequent event in melanoma progression. Here, we investigated DEK expression by immunohistochemistry in a total of 147 melanocytic lesions, including ordinary nevi, dysplastic nevi, Spitz nevi, melanoma in situ, primary invasive melanomas, and metastatic melanomas. Most benign nevi (ordinary, dysplastic, and Spitz nevi) were negative or exhibited weak staining for DEK, with only 4 of 49 cases showing strong staining. Similar to benign nevi, melanoma in situ also demonstrated low levels of DEK expression. In contrast, the expression of DEK in primary invasive melanomas was significantly higher than benign nevi (P < .0001). Moreover, DEK expression was significantly increased in deep melanomas (Bres...

Research paper thumbnail of Expression of the embryonic morphogen Nodal in cutaneous melanocytic lesions

Modern Pathology, 2010

Nodal, a potent embryonic morphogen in the transforming growth factor-b family, is a proposed key... more Nodal, a potent embryonic morphogen in the transforming growth factor-b family, is a proposed key regulator of melanoma tumorigenicity. However, there has been no systematic study of Nodal expression in melanocytic lesions. We investigated Nodal expression by immunohistochemistry in 269 melanocytic lesions, including compound nevi, dysplastic nevi, congenital nevi, Spitz nevi, melanoma in situ, malignant melanoma including the variant desmoplastic melanoma, and metastatic melanoma. We found that the Nodal expression was significantly increased in malignant lesions (including melanoma in situ, malignant melanoma, and metastatic melanoma) compared with compound nevi, Spitz nevi, and dysplastic nevi. Surprisingly, congenital nevi expressed a level of Nodal comparable with malignant lesions, whereas desmoplastic melanoma showed lower expression than nondesmoplastic malignant melanoma (Po0.05). Deep melanoma (Breslow depth 41 mm) displayed a higher percentage of Nodal-positive tumor cells than did superficial melanoma (Breslow depth r1 mm), although there was no statistical difference in the overall staining intensity (P ¼ 0.18). Melanomas in situ showed a lower level of Nodal expression than did deep melanomas and metastatic melanomas (Po0.05). The low expression of Nodal in normal and dysplastic nevi, and its increasing expression with the progression of malignant lesions, are suggestive of a role for Nodal in melanoma progression.

Research paper thumbnail of Diagnostic utility of IMP3 in segregating metastatic melanoma from benign nevi in lymph nodes

Modern Pathology, 2009

Depending on the Breslow depth of the primary melanoma, sentinel lymph node biopsy is considered ... more Depending on the Breslow depth of the primary melanoma, sentinel lymph node biopsy is considered as standard of care for the staging of cutaneous melanoma, and is one of the most important prognostic factors. The histologic analysis of these specimens becomes difficult to interpret when benign intranodal nevic cells mimic metastases. Insulin-like growth factor-II messenger RNA (mRNA)-binding protein-3 (IMP3), also known as K homology domain-containing protein overexpressed in cancer or L523S, is a member of the insulin-like growth factor-II mRNA-binding protein family and has been shown to have diagnostic utility in distinguishing cutaneous melanoma from benign nevi. In this study, 43 sentinel lymph node biopsy specimens, including 13 with benign intranodal nevi and 30 with metastatic melanoma (two cases containing both benign nevi and metastatic melanoma), from 41 patients were immunohistochemically analyzed with a monoclonal antibody against IMP3. None of the benign intranodal nevi expressed IMP3, whereas 21 out of 30 (70%) of the lymph nodes containing metastatic melanoma did. It seems that IMP3 is helpful in distinguishing benign intranodal nevi from metastatic melanoma in sentinel lymph node biopsy specimens, and could be a valuable diagnostic adjunct in sentinel lymph node biopsy assessment in which questions arise as to the malignancy of the melanocytes present.

Research paper thumbnail of Cutaneous Richter syndrome: Report of 3 cases from one institution

Journal of the American Academy of Dermatology, 2012

Richter syndrome (RS) is large-cell transformation of chronic lymphocytic leukemia (CLL). It comm... more Richter syndrome (RS) is large-cell transformation of chronic lymphocytic leukemia (CLL). It commonly involves lymph nodes and bone marrow, but may rarely manifest in skin. Certain triggering factors, such as Epstein-Barr virus infection and p53 overexpression, have been implicated in the pathogenesis of RS. Here, we present 3 cases of cutaneous RS from our institution with a follow-up period of up to 8 years. We present a series of cutaneous RS from a single institution with the longest follow-up period (up to 8 years) to date. Clinical characteristics were collected and histopathological findings of skin biopsy specimens were analyzed. All 3 patients had prior CLL and later developed cutaneous RS lesions. The mean age at the diagnosis of cutaneous RS was 67 years old. The time intervals between CLL and cutaneous RS were 3 to 8 years. Skin biopsy specimens demonstrated dermal nodular or perivascular infiltrates of large B cells, showing similar immunophenotypes to the lesional cells in the original CLL. Overexpression of p53 and positive stain for Epstein-Barr virus--encoded small RNA was found in one patient. One patient remained alive 8 years after the diagnosis whereas the other two died of the disease at 5 years and 3 weeks, respectively, after the onset of cutaneous RS. Three patients with RS were followed up for up to 8 years. Our findings suggested that, in contrast to extracutaneous RS, cutaneous RS generally has a less aggressive course with longer survival unless other worse prognostic factors are present.

Research paper thumbnail of Continuing Medical Education Article Comparison of CD23 staining patterns in Merkel cell carcinoma and non-cutaneous small cell carcinoma

Background: During our daily practice, we observed that cluster designation 23 (CD23) (clone BU38... more Background: During our daily practice, we observed that cluster designation 23 (CD23) (clone BU38) labels Merkel cells in normal skin. In this study, we examined the expression of CD23 in Merkel cell carcinoma (MCC) and assessed its usefulness in distinguishing MCC from non-cutaneous small cell carcinoma (SMCC). Methods: Immunohistochemical staining of CD23 was performed on a total of 33 MCCs, 22 SMCCs and 5 carcinoid tumors. Results: CD23 reactivity was present in 32 of 33 (97%) MCCs, 18 of 22 (82%) SMCCs and 5 of 5 (100%) carcinoid tumors. In MCC, 19 cases (59%) showed a predominance of perinuclear dot-like staining similar to cytokeratin 20, 3 (9%) showed mostly cytoplasmic staining and 10 (31%) displayed a combination of perinuclear dot-like and cytoplasmic staining. In contrast, all CD23-positive SMCCs and carcinoid tumors showed a diffuse cytoplasmic staining. There was a significant difference in the CD23 staining patterns between MCC and SMCC (p , 0.0001). Conclusion: CD23 i...

Research paper thumbnail of CD163 expression in leukemia cutis

Journal of Cutaneous Pathology, 2010

Proper diagnosis of myeloid leukemia cutis (LC) is of great clinical importance but can be diffic... more Proper diagnosis of myeloid leukemia cutis (LC) is of great clinical importance but can be difficult because no single immunohistochemical marker is adequately sensitive or specific for definitive diagnosis. Thus, a broader panel of markers is often desirable. CD163 is highly specific for normal and neoplastic cells of the monocyte/histiocyte lineage. In this study, we examined the value of CD163 in the diagnosis of acute myeloid LC. A total of 34 cases, including 18 cases of myelomonocytic or monocytic LC, 10 cases of myeloid LC without monocytic component and 6 cases of acute lymphoblastic leukemia/lymphoma (ALL), were stained with CD163. CD163 was expressed in 8 of 18 (44%) of myelomonocytic or monocytic LC and 1 of 10 (10%) of other myeloid LC, but in none of the ALL cases (0/6). CD163 was highly specific (90%) for myeloid LC with a monocytic component, but showed low sensitivity in the diagnosis of both myeloid LC in general (24%) and myeloid LC with a monocytic component (44%). Our results suggest that CD163 has utility as a specific marker for myeloid LC in conjunction with currently used immunohistochemical stains, but should not be used alone for diagnosis.

Research paper thumbnail of Diagnostic value of CD163 in cutaneous spindle cell lesions

Journal of Cutaneous Pathology, 2009

Background: The histologic diagnosis of atypical fibroxanthoma (AFX) can sometimes be challenging... more Background: The histologic diagnosis of atypical fibroxanthoma (AFX) can sometimes be challenging. No specific marker exists to confirm the diagnosis other than excluding other entities. CD163 has been shown to have great specificity for tumors of monocyte/histiocyte lineage. In this study, we evaluated the diagnostic utility of CD163 in diagnosing AFX and in identifying skin lesions with histiocytic/ dendritic derivation. Methods: A total of 157 cases, including 14 AFXs, 5 spindle cell squamous cell carcinomas (SCCs), and 7 spindle cell/desmoplastic melanomas, along with other cutaneous spindle cell and histiocytic/ fibrohistiocytic lesions, were stained with CD163. Results: CD163 was expressed in 11 of 14 (79%) AFXs, with moderate to strong intensity. No staining was observed in cases of spindle cell SCC (0/5) and dermatofibrosarcoma protuberans (0/10). Rare spindle cell/desmoplastic melanomas (2/7) and cutaneous leiomyosarcomas (1/5) demonstrated positive staining. CD163 reactivity was seen in 24 of 29 of benign fibrous histiocytomas (BFHs), including 8 of 8 celular fibrous histiocytomas and 6 of 9 epithelioid cell histiocytomas. The majority of cutaneous histiocytic lesions, including juvenile xanthogranuloma, Langerhans cell histiocytosis and Rosai-Dorfman disease, were positive for CD163. Conclusion: CD163 is a useful adjunct in distinguishing AFX from other malignant cutaneous spindle cell tumors and offers improved specificity in identifying cutaneous histiocytic/dendritic lesions.

Research paper thumbnail of The expression of CD23 in cutaneous non-lymphoid neoplasms

Journal of Cutaneous Pathology, 2007

Research paper thumbnail of IMP-3 expression in melanocytic lesions

Journal of Cutaneous Pathology, 2010

Insulin-like growth factor-II mRNA-binding protein 3 (IMP-3 ), a member of the insulin-like growt... more Insulin-like growth factor-II mRNA-binding protein 3 (IMP-3 ), a member of the insulin-like growth factor mRNA-binding protein family, is expressed in several human malignancies, including melanomas. However, the expression of IMP-3 has not been explored in melanoma in situ, various histologic subtypes of invasive melanomas and atypical Spitz tumors. IMP-3 immunostain was performed in 157 melanocytic lesions. Nearly all benign (8/8), dysplastic (8/8) and Spitz nevi (8/9) were negative for IMP-3. Focal IMP-3 positivity was observed in 5/12 melanoma in situ and 4/15 superficial melanomas (Breslow depth &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;or=1 mm). Half (10/20) of deep melanomas (Breslow depth &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;1 mm) and 25/52 metastatic melanomas demonstrated strong IMP-3 staining. IMP-3 expression differs significantly between non-desmoplastic melanomas (superficial and deep) and benign or dysplastic or Spitz nevi (p = 0.0427, respectively). Four of 23 desmoplastic melanomas expressed IMP-3 , which was significantly different from deep melanomas (p = 0.0109). IMP-3 stained 7 of 10 atypical Spitz tumors. The difference between atypical Spitz tumors and Spitz nevi was statistically significant (p = 0.0256). A malignant circumstance, such as non-desmoplastic melanoma or atypical Spitz tumor, can be inferred when IMP-3 is expressed, suggesting potential diagnostic value of IMP-3 in melanocytic lesions.

Research paper thumbnail of Fatal Subcutaneous Panniculitis-Like T-Cell Lymphoma (Sptcl) with Interface Change and Dermal Mucin, A Dead-Ringer for Lupus Erythematosus

Journal of Cutaneous Pathology, 2008

ABSTRACT We report a 48-year-old man who presented with ulcerated plaques and nodules of the lowe... more ABSTRACT We report a 48-year-old man who presented with ulcerated plaques and nodules of the lower extremities. Skin biopsies revealed a dense lymphocytic infiltrate involving the dermis and the subcutis in a lobular and septal pattern. No overt cytological atypia was present. Notably, several features resembling lupus erythematosus were present, including vacuolar interface change and abundant dermal mucin deposition. The patient developed pulmonary nodules, and a lung biopsy showed a perivascular and interstitial lymphoid infiltrate without overt atypia. The cutaneous and pulmonary lymphoid infiltrates showed similar immunohistochemical profiles: CD3(+) CD4(-) CD8(+/-) CD56(+). Monoclonal rearrangements of the T-cell receptor gamma gene with similar migration patterns were identified from both locations. The patient developed fatal hemophagocytic syndrome, involving liver, spleen, lymph nodes, and bone marrow. This case is one amongst the rare reports of subcutaneous panniculitis-like T-cell lymphoma with systemic involvement.

Research paper thumbnail of Atypical fibroxanthoma with lymphomatoid reaction

Journal of Cutaneous Pathology, 2011

Atypical fibroxanthoma (AFX) represents an uncommon skin tumor typically occurring on sun-damaged... more Atypical fibroxanthoma (AFX) represents an uncommon skin tumor typically occurring on sun-damaged skin of the elderly. Histopathologic variants include spindled, clear cell, osteoid, osteoclastic, chondroid, pigmented, granular cell and myxoid lesions. To date, an atypical lymphoid infiltrate, including CD30-positive large cells mimicking lymphomatoid papulosis, has not been described in association with AFX. The clinical and histopathological characteristics of two AFX cases inciting an atypical lymphoid infiltrate, along with immunohistochemical profiles and T-cell receptor gamma (TCRγ) gene rearrangement results, were reviewed. Lesions in both cases occurred as solitary nodules in elderly patients. Microscopically, both lesions showed a cellular proliferation composed of pleomorphic spindle cells, associated with a prominent intralesional atypical lymphoid infiltrate. The spindle cells expressed CD10 but lacked the expression of S-100, cytokeratins and muscle markers, thereby confirming the diagnosis of AFX. CD30 highlighted a significant subset of large mononuclear cells in the lymphoid infiltrate of one case. TCRγ gene rearrangement analyses were negative for both cases. An atypical lymphoid infiltrate, including the one resembling lymphomatoid papulosis, associated with AFX has not been previously described. It is important to recognize the reactive nature of the infiltrate to avoid a misdiagnosis of lymphoma.