Mai Hoàng - Academia.edu (original) (raw)

Papers by Mai Hoàng

Journal of Cutaneous Pathology, 2012

Asia Pacific Business Review, 2015

Advances in Natural Sciences: Nanoscience and Nanotechnology, 2011

Macromolecular Research, 2013

Medical Hypotheses, 2005

Mammalian fatty acid synthase (FASE) overexpression has been shown in a number of human malignanc... more Mammalian fatty acid synthase (FASE) overexpression has been shown in a number of human malignancies including colonic adenocarcinoma. Since FASE synthesizes only saturated fatty acids, we hypothesized that cancer cells have a greater proportion of long-chain saturated fatty acids. We studied and found an unequivocal increase in saturated C18 fatty acid (stearic acid) in colonic adenocarcinoma compared to adjacent normal colonic mucosa. The increase is even more striking when measured as a ratio of stearic acid to the unsaturated C18 fatty acids (oleic acid and linoleic acid). This change in fatty acid composition of the cancer cells should significantly alter their physical and biological properties. The increase in relative proportion of saturated fatty acids should make the cancer cells more susceptible to cryodamage and measurement of fatty acid composition of cancer cells may help individualize the temperature for cryotherapy. Also, the lipid alterations may affect the structure and functions of lipid rafts, which may enable the cancer cells to affect signaling mechanisms such as those involved in cell growth and apoptosis. Dietary or therapeutic interventions targeting lipid rafts may thus be an option for cancer treatment.

Journal of Cutaneous Pathology, 2003

Background: The deposition of extracellular mucin has not been described in Spitz nevus and here... more Background: The deposition of extracellular mucin has not been described in Spitz nevus and herein such a case is reported.Methods: A 6-year-old male presented with a growing 1.0-cm pigmented lesion on his left anterior knee. The lesion was excised.Results: The histologic sections demonstrated a symmetrical and dome-shaped proliferation of spindle and epithelioid melanocytes with sharp lateral demarcation at the dermal–epidermal junction and within the superficial dermis. Features of Spitz nevus such as retraction from the epidermis, eosinophilic bodies, and uniform cytologic atypia were seen. Of interest, there was marked mucin deposition within the epidermal clefts and between the neoplastic cells.The mucin was highlighted by alcian blue and colloidal iron stains, and it was negative with mucicarmine and periodic acid–Schiff stains.Conclusion: Awareness that soitz nevi can rarely have extracellular mucin helps in avoiding diagnostic pitfalls.

Annals of Diagnostic Pathology, 2002

Giant cell tumor (GCT) of the skin is a rare entity that possesses similar gross and histologic f... more Giant cell tumor (GCT) of the skin is a rare entity that possesses similar gross and histologic features to GCT of bone. When located predominantly in the dermis GCT has been mistaken for benign fibrous histiocytoma and atypical fibroxanthoma. We report the clinical, morphologic, and immunohistochemical features of five cases of GCT of the skin. With one exception, all tumors are confined to the dermis. Patients' ages range from 6 to 78 years (median, 73 years) with a male to female ratio of 3:2. Gross and histologic features of the lesions are similar to those of GCT of bone (eg, brown fleshy tumor and a biphasic population of mononuclear cells admixed with osteoclast-like giant cells, respectively). The nuclei of the giant cells are similar to those of the mononuclear cells. A fascicular pattern with focal storiform arrangement of spindle neoplastic cells is noted in two cases. The osteoclast-like giant cells and some of the mononuclear cells are strongly positive for CD68, alpha-1-antitrypsin, and alpha-1-antichymotrypsin. Only the mononuclear cells express smooth muscle actin focally in one case. Both the osteoclast-like giant cells and the mononuclear cells are negative for cytokeratins (AE1/AE3 and CAM5.2) and S-100 protein in all cases. One patient developed lung metastases at presentation and local recurrence 4 months status post surgery. All patients are without evidence of disease 1 month to 12 years status post surgery. Cutaneous GCTs are low-grade sarcomas that can recur locally and infrequently metastasize. These tumors should be distinguished from a variety of cutaneous neoplasms that contain multinucleated giant cells. Ann Diagn Pathol 6:288-293, 2002.

Human Pathology, 2001

Primary small-cell carcinoma of the breast is an exceedingly rare variant of breast carcinoma who... more Primary small-cell carcinoma of the breast is an exceedingly rare variant of breast carcinoma whose genetic profile has not been previously investigated. We report the molecular features of 2 cases of small-cell carcinoma of the breast: 1 with an adjacent intraductal carcinoma, and 1 with prior pleomorphic lobular carcinoma in situ. Laser capture microdissection followed by loss of heterozygosity (LOH) analysis revealed identical molecular alterations at multiple chromosomal regions, including BRCA-1, BRCA-2, p53, and retinoblastoma gene loci, in 1 case of small-cell carcinoma and its adjacent intraductal component. Additionally, LOH in 1 or both small-cell carcinomas was detected at 3p, 4q31.2-qter, 8p21-24, 11q13 (MEN-1 locus), 11q23.3, 11q24.1-25, 16q24.1 (H-cadherin locus), and 17q25. The results of our molecular analysis suggest that genetic changes in mammary small-cell carcinoma resembled those seen in both invasive ductal carcinomas and pulmonary small-cell carcinoma. Second, mammary small-cell carcinoma is clonally related to ductal carcinoma in situ and might represent an example of divergent differentiation occuring in a multipotential neoplastic stem cell. HUM PATHOL 32:753-757. Copyright © 2001 by W.B. Saunders Company

Journal of The American Academy of Dermatology, 2005

Lipedematous alopecia is a rare entity of uncertain origin characterized by a boggy scalp and var... more Lipedematous alopecia is a rare entity of uncertain origin characterized by a boggy scalp and varying alopecia. Of 11 cases in the literature, 7 occurred in African American women. Classic histopathologic findings include increased subcutaneous tissue, varying inflammation, and an absence of mucin. Some have sought to distinguish this disorder from lipedematous scalp, a condition with similar tactile features, but without alopecia.We describe a case of lipedematous alopecia in an African American woman who also had findings of discoid lupus erythematosus. Such an observation has not been made previously, and may provide insight into the cause of lipedematous alopecia. This case is contrasted with a case of lipedematous scalp.Some cases of lipedematous alopecia may represent an unusual consequence of discoid lupus erythematosus. Alternatively, it is possible that lipedematous scalp is a benign condition observed in some patients, and that a second insult results in alopecia. Finally, lipedematous alopecia might share some histopathologic and/or clinical findings with discoid lupus erythematosus, or it may represent a nonspecific reaction pattern to chronic injury.

Journal of Cutaneous Pathology, 2001

Background: Recurrent melanocytic lesions may histologically resemble malignant melanoma.Methods:... more Background: Recurrent melanocytic lesions may histologically resemble malignant melanoma.Methods: We evaluated the original nevi (ON) and recurrent nevi (RN) of 15 patients by routine histology and immunohistochemistry (IHC), examining expression of S-100 protein, gp100 (with HMB-45), MART-1, tyrosinase, and the Ki-67 proliferation marker.Results: Compared with ON, RN had a dermal scar, a significantly greater number of melanophages, and a greater extent of cellular atypia including prominent nucleoli and larger cell size. Architecturally, RN showed significantly less symmetry than ON; however, the percentage of junctional cohesive nests, the presence of suprabasal spread, and the degree of confluence were similar between ON and RN. Both ON and RN showed a decrease in expression of gp100 and tyrosinase with increasing depth (“maturation gradient”) and low proliferative activity in both the junctional (4.6% for ON vs. 4.13% for RN) and the dermal components (0.93% for ON vs. 1.45% for RN).Conclusions: RN exhibit a dermal scar, a greater number of melanophages, cytologic atypia, and asymmetry than ON, features that may raise concern about the possibility of malignant melanoma. However, the area with the irregular architectural pattern is restricted to the epidermis and dermis immediately above the scar. In addition, IHC helps to distinguish RN from malignant melanoma; specifically, RN demonstrate an immunohistochemical “maturation pattern” (with HMB-45 and anti-tyrosinase) and a low proliferative index (with Ki-67).

Journal of Cutaneous Pathology, 2001

Background: Primary and metastatic malignant melanoma can simulate various soft tissue tumors, in... more Background: Primary and metastatic malignant melanoma can simulate various soft tissue tumors, including dermatofibrosarcoma protuberans (DFSP). Expression of CD34, a marker characteristic of DFSP, as well as other spindle cell tumors, has not been previously documented in malignant melanoma.Methods: We present here an unusual case of metastatic malignant melanoma with a strong histologic resemblance to DFSP and also CD34 expression.Results: The patient, a 72-year-old man with a history of an invasive malignant melanoma of the skin of the right lower abdomen, presented with a right axillary mass. Histologic sections revealed intersecting fascicles of spindle cells with nuclear pleomorphism and numerous mitotic figures, diffusely infiltrating the adipose tissue in a pattern closely simulating that seen in DFSP. In other foci, epithelioid neoplastic cells with abundant cytoplasm, prominent nucleoli, nuclear pseudoinclusions, and focal cytoplasmic melanin pigment were seen. The neoplastic spindle cells were strongly labeled by two anti-CD34 monoclonal antibodies. Some of the spindle cells and the majority of the epithelioid neoplastic cells expressed S-100 protein and focally tyrosinase. The tumor cells were negative for HMB-45 and MART-1. Melanosomes were not identified by electron microscopy.Conclusion: This case demonstrates the potential of melanoma to simulate DFSP closely, on both morphologic and immunohistochemical grounds, and confirms the utility of employing a broad panel of immunohistochemical reagents in problematic cases.

Journal of The American Academy of Dermatology, 2004

The West Nile Virus (WNV) has rapidly emerged as an important etiology of meningoencephalitis in ... more The West Nile Virus (WNV) has rapidly emerged as an important etiology of meningoencephalitis in North America since 1999. Diagnosis of this infection on clinical grounds is difficult, as many signs and symptoms of infection are nonspecific. Although cutaneous manifestations are common in WNV-infected patients, these have not been described in detail nor are clinical images widely available. We describe 3 patients with WNV infections, two ambulatory, one hospitalized, who developed punctate erythematous, macular, and papular eruptions, most pronounced on the extremities. Histopathologic findings in one case showed a sparse superficial perivascular lymphocytic infiltrate, a feature commonly seen in viral exanthems but not previously reported with WNV infection. A literature review provides support that this punctate exanthem is a common cutaneous presentation of WNV infection.

Modern Pathology, 2001

Although metaplastic changes can occur in the extrahepatic bile ducts, a detailed morphologic stu... more Although metaplastic changes can occur in the extrahepatic bile ducts, a detailed morphologic study of these lesions has not been done. We examined the bile duct mucosa in 42 pancreaticoduodenectomy specimens, 32 with neoplastic lesions and ten with inflammatory lesions of the extrahepatic bile ducts, to assess the prevalence and type of metaplastic lesions. For comparison, the common bile ducts from 10 autopsy cases were reviewed. Twenty of the 42 total cases (48%), 13 of the 32 neoplastic cases (40%), and 7 of the 10 inflammatory cases (70%) had metaplastic changes. Pyloric gland metaplasia was the most common type (16/20 cases; 80%), whereas intestinal metaplasia was seen in 1/20 cases (5%). A combination of pyloric gland and intestinal metaplasia occurred in 2/20 cases (10%), and squamous metaplasia plus the above-mentioned two types of metaplasia was seen in 1/20 cases (5%). None of the normal common bile ducts obtained from ten autopsies had metaplastic changes. Endocrine cells were identified in nine (56%) of 17 metaplastic lesions. In contrast, endocrine cells within the intramural glands were seen in only 2 of the 10 normal common bile ducts. Although a significant proportion of carcinomas (6/13 cases) was in close proximity to areas of metaplasia, we were unable to find dysplastic foci within the metaplastic glands or the metaplastic surface epithelium. Reactive atypical cells involved the surface biliary epithelium and intramural glands and were associated with inflammation and metaplastic changes. The presence of goblet, mucinous, squamous, and reactive atypical cells in association with hyperplasia of intramural glands in frozen sections or small biopsy specimens may be mistaken for malignancy; hence, recognition of these lesions is of diagnostic importance.

Human Pathology, 2015

BAP1 (BRCA1-associated protein 1) is a tumor suppressor gene whose mutations have recently been r... more BAP1 (BRCA1-associated protein 1) is a tumor suppressor gene whose mutations have recently been reported to increase susceptibility for the development of uveal melanoma, cutaneous atypical and epithelioid melanocytic lesions, clear cell renal cell carcinoma, and other tumors. Screening for BAP1 mutation/loss/inactivation and BRAFV600E mutation can be done by immunohistochemistry. We investigated BAP1 and BRAFV600E expression in 193 sporadic melanocytic lesions (11 dermal nevi, 20 congenital nevi, 40 primary and nondesmoplastic melanomas, 40 desmoplastic melanomas, 23 metastatic melanomas, 17 Spitz nevi, 19 atypical Spitz nevi, 8 atypical Spitz tumors, 14 proliferative nodules arising in congenital nevi, 1 nevus during pregnancy) and 30 melanocytic lesions from 3 patients with family history of uveal melanoma and BAP1 germline mutation. Most sporadic melanocytic lesions exhibited positive BAP1 nuclear staining, except for 1 proliferative nodule arising in congenital nevus, 1 desmoplastic, 1 nevoid, and 2 metastatic melanomas. BRAFV600E positivity was demonstrated in 80% of dermal, 5% of congenital, 6% of Spitz, and 5.5% of atypical Spitz nevi; 29% of proliferative nodules arising in congenital nevi; and 24% of primary and nondesmoplastic and 35% of metastatic melanomas. Combined BAP1 loss and BRAFV600E staining was seen in 67% of BAP1 tumor syndrome-associated lesions and in none of the sporadic melanocytic proliferations including Spitz and atypical Spitz nevi and atypical Spitz tumors, with the exception of 1 primary melanoma. The combined BAP1-BRAFV600E+ immunoprofile appears to be a constant feature of BAP1 tumor syndrome-associated melanocytic lesions, and the designation of Spitz nevi or variants thereof appears to be inaccurate for this group of lesions.

Melanocytic Lesions, 2014

Journal of Cutaneous Pathology, 2012

Asia Pacific Business Review, 2015

Advances in Natural Sciences: Nanoscience and Nanotechnology, 2011

Macromolecular Research, 2013

Medical Hypotheses, 2005

Mammalian fatty acid synthase (FASE) overexpression has been shown in a number of human malignanc... more Mammalian fatty acid synthase (FASE) overexpression has been shown in a number of human malignancies including colonic adenocarcinoma. Since FASE synthesizes only saturated fatty acids, we hypothesized that cancer cells have a greater proportion of long-chain saturated fatty acids. We studied and found an unequivocal increase in saturated C18 fatty acid (stearic acid) in colonic adenocarcinoma compared to adjacent normal colonic mucosa. The increase is even more striking when measured as a ratio of stearic acid to the unsaturated C18 fatty acids (oleic acid and linoleic acid). This change in fatty acid composition of the cancer cells should significantly alter their physical and biological properties. The increase in relative proportion of saturated fatty acids should make the cancer cells more susceptible to cryodamage and measurement of fatty acid composition of cancer cells may help individualize the temperature for cryotherapy. Also, the lipid alterations may affect the structure and functions of lipid rafts, which may enable the cancer cells to affect signaling mechanisms such as those involved in cell growth and apoptosis. Dietary or therapeutic interventions targeting lipid rafts may thus be an option for cancer treatment.

Journal of Cutaneous Pathology, 2003

Background: The deposition of extracellular mucin has not been described in Spitz nevus and here... more Background: The deposition of extracellular mucin has not been described in Spitz nevus and herein such a case is reported.Methods: A 6-year-old male presented with a growing 1.0-cm pigmented lesion on his left anterior knee. The lesion was excised.Results: The histologic sections demonstrated a symmetrical and dome-shaped proliferation of spindle and epithelioid melanocytes with sharp lateral demarcation at the dermal–epidermal junction and within the superficial dermis. Features of Spitz nevus such as retraction from the epidermis, eosinophilic bodies, and uniform cytologic atypia were seen. Of interest, there was marked mucin deposition within the epidermal clefts and between the neoplastic cells.The mucin was highlighted by alcian blue and colloidal iron stains, and it was negative with mucicarmine and periodic acid–Schiff stains.Conclusion: Awareness that soitz nevi can rarely have extracellular mucin helps in avoiding diagnostic pitfalls.

Annals of Diagnostic Pathology, 2002

Giant cell tumor (GCT) of the skin is a rare entity that possesses similar gross and histologic f... more Giant cell tumor (GCT) of the skin is a rare entity that possesses similar gross and histologic features to GCT of bone. When located predominantly in the dermis GCT has been mistaken for benign fibrous histiocytoma and atypical fibroxanthoma. We report the clinical, morphologic, and immunohistochemical features of five cases of GCT of the skin. With one exception, all tumors are confined to the dermis. Patients' ages range from 6 to 78 years (median, 73 years) with a male to female ratio of 3:2. Gross and histologic features of the lesions are similar to those of GCT of bone (eg, brown fleshy tumor and a biphasic population of mononuclear cells admixed with osteoclast-like giant cells, respectively). The nuclei of the giant cells are similar to those of the mononuclear cells. A fascicular pattern with focal storiform arrangement of spindle neoplastic cells is noted in two cases. The osteoclast-like giant cells and some of the mononuclear cells are strongly positive for CD68, alpha-1-antitrypsin, and alpha-1-antichymotrypsin. Only the mononuclear cells express smooth muscle actin focally in one case. Both the osteoclast-like giant cells and the mononuclear cells are negative for cytokeratins (AE1/AE3 and CAM5.2) and S-100 protein in all cases. One patient developed lung metastases at presentation and local recurrence 4 months status post surgery. All patients are without evidence of disease 1 month to 12 years status post surgery. Cutaneous GCTs are low-grade sarcomas that can recur locally and infrequently metastasize. These tumors should be distinguished from a variety of cutaneous neoplasms that contain multinucleated giant cells. Ann Diagn Pathol 6:288-293, 2002.

Human Pathology, 2001

Primary small-cell carcinoma of the breast is an exceedingly rare variant of breast carcinoma who... more Primary small-cell carcinoma of the breast is an exceedingly rare variant of breast carcinoma whose genetic profile has not been previously investigated. We report the molecular features of 2 cases of small-cell carcinoma of the breast: 1 with an adjacent intraductal carcinoma, and 1 with prior pleomorphic lobular carcinoma in situ. Laser capture microdissection followed by loss of heterozygosity (LOH) analysis revealed identical molecular alterations at multiple chromosomal regions, including BRCA-1, BRCA-2, p53, and retinoblastoma gene loci, in 1 case of small-cell carcinoma and its adjacent intraductal component. Additionally, LOH in 1 or both small-cell carcinomas was detected at 3p, 4q31.2-qter, 8p21-24, 11q13 (MEN-1 locus), 11q23.3, 11q24.1-25, 16q24.1 (H-cadherin locus), and 17q25. The results of our molecular analysis suggest that genetic changes in mammary small-cell carcinoma resembled those seen in both invasive ductal carcinomas and pulmonary small-cell carcinoma. Second, mammary small-cell carcinoma is clonally related to ductal carcinoma in situ and might represent an example of divergent differentiation occuring in a multipotential neoplastic stem cell. HUM PATHOL 32:753-757. Copyright © 2001 by W.B. Saunders Company

Journal of The American Academy of Dermatology, 2005

Lipedematous alopecia is a rare entity of uncertain origin characterized by a boggy scalp and var... more Lipedematous alopecia is a rare entity of uncertain origin characterized by a boggy scalp and varying alopecia. Of 11 cases in the literature, 7 occurred in African American women. Classic histopathologic findings include increased subcutaneous tissue, varying inflammation, and an absence of mucin. Some have sought to distinguish this disorder from lipedematous scalp, a condition with similar tactile features, but without alopecia.We describe a case of lipedematous alopecia in an African American woman who also had findings of discoid lupus erythematosus. Such an observation has not been made previously, and may provide insight into the cause of lipedematous alopecia. This case is contrasted with a case of lipedematous scalp.Some cases of lipedematous alopecia may represent an unusual consequence of discoid lupus erythematosus. Alternatively, it is possible that lipedematous scalp is a benign condition observed in some patients, and that a second insult results in alopecia. Finally, lipedematous alopecia might share some histopathologic and/or clinical findings with discoid lupus erythematosus, or it may represent a nonspecific reaction pattern to chronic injury.

Journal of Cutaneous Pathology, 2001

Background: Recurrent melanocytic lesions may histologically resemble malignant melanoma.Methods:... more Background: Recurrent melanocytic lesions may histologically resemble malignant melanoma.Methods: We evaluated the original nevi (ON) and recurrent nevi (RN) of 15 patients by routine histology and immunohistochemistry (IHC), examining expression of S-100 protein, gp100 (with HMB-45), MART-1, tyrosinase, and the Ki-67 proliferation marker.Results: Compared with ON, RN had a dermal scar, a significantly greater number of melanophages, and a greater extent of cellular atypia including prominent nucleoli and larger cell size. Architecturally, RN showed significantly less symmetry than ON; however, the percentage of junctional cohesive nests, the presence of suprabasal spread, and the degree of confluence were similar between ON and RN. Both ON and RN showed a decrease in expression of gp100 and tyrosinase with increasing depth (“maturation gradient”) and low proliferative activity in both the junctional (4.6% for ON vs. 4.13% for RN) and the dermal components (0.93% for ON vs. 1.45% for RN).Conclusions: RN exhibit a dermal scar, a greater number of melanophages, cytologic atypia, and asymmetry than ON, features that may raise concern about the possibility of malignant melanoma. However, the area with the irregular architectural pattern is restricted to the epidermis and dermis immediately above the scar. In addition, IHC helps to distinguish RN from malignant melanoma; specifically, RN demonstrate an immunohistochemical “maturation pattern” (with HMB-45 and anti-tyrosinase) and a low proliferative index (with Ki-67).

Journal of Cutaneous Pathology, 2001

Background: Primary and metastatic malignant melanoma can simulate various soft tissue tumors, in... more Background: Primary and metastatic malignant melanoma can simulate various soft tissue tumors, including dermatofibrosarcoma protuberans (DFSP). Expression of CD34, a marker characteristic of DFSP, as well as other spindle cell tumors, has not been previously documented in malignant melanoma.Methods: We present here an unusual case of metastatic malignant melanoma with a strong histologic resemblance to DFSP and also CD34 expression.Results: The patient, a 72-year-old man with a history of an invasive malignant melanoma of the skin of the right lower abdomen, presented with a right axillary mass. Histologic sections revealed intersecting fascicles of spindle cells with nuclear pleomorphism and numerous mitotic figures, diffusely infiltrating the adipose tissue in a pattern closely simulating that seen in DFSP. In other foci, epithelioid neoplastic cells with abundant cytoplasm, prominent nucleoli, nuclear pseudoinclusions, and focal cytoplasmic melanin pigment were seen. The neoplastic spindle cells were strongly labeled by two anti-CD34 monoclonal antibodies. Some of the spindle cells and the majority of the epithelioid neoplastic cells expressed S-100 protein and focally tyrosinase. The tumor cells were negative for HMB-45 and MART-1. Melanosomes were not identified by electron microscopy.Conclusion: This case demonstrates the potential of melanoma to simulate DFSP closely, on both morphologic and immunohistochemical grounds, and confirms the utility of employing a broad panel of immunohistochemical reagents in problematic cases.

Journal of The American Academy of Dermatology, 2004

The West Nile Virus (WNV) has rapidly emerged as an important etiology of meningoencephalitis in ... more The West Nile Virus (WNV) has rapidly emerged as an important etiology of meningoencephalitis in North America since 1999. Diagnosis of this infection on clinical grounds is difficult, as many signs and symptoms of infection are nonspecific. Although cutaneous manifestations are common in WNV-infected patients, these have not been described in detail nor are clinical images widely available. We describe 3 patients with WNV infections, two ambulatory, one hospitalized, who developed punctate erythematous, macular, and papular eruptions, most pronounced on the extremities. Histopathologic findings in one case showed a sparse superficial perivascular lymphocytic infiltrate, a feature commonly seen in viral exanthems but not previously reported with WNV infection. A literature review provides support that this punctate exanthem is a common cutaneous presentation of WNV infection.

Modern Pathology, 2001

Although metaplastic changes can occur in the extrahepatic bile ducts, a detailed morphologic stu... more Although metaplastic changes can occur in the extrahepatic bile ducts, a detailed morphologic study of these lesions has not been done. We examined the bile duct mucosa in 42 pancreaticoduodenectomy specimens, 32 with neoplastic lesions and ten with inflammatory lesions of the extrahepatic bile ducts, to assess the prevalence and type of metaplastic lesions. For comparison, the common bile ducts from 10 autopsy cases were reviewed. Twenty of the 42 total cases (48%), 13 of the 32 neoplastic cases (40%), and 7 of the 10 inflammatory cases (70%) had metaplastic changes. Pyloric gland metaplasia was the most common type (16/20 cases; 80%), whereas intestinal metaplasia was seen in 1/20 cases (5%). A combination of pyloric gland and intestinal metaplasia occurred in 2/20 cases (10%), and squamous metaplasia plus the above-mentioned two types of metaplasia was seen in 1/20 cases (5%). None of the normal common bile ducts obtained from ten autopsies had metaplastic changes. Endocrine cells were identified in nine (56%) of 17 metaplastic lesions. In contrast, endocrine cells within the intramural glands were seen in only 2 of the 10 normal common bile ducts. Although a significant proportion of carcinomas (6/13 cases) was in close proximity to areas of metaplasia, we were unable to find dysplastic foci within the metaplastic glands or the metaplastic surface epithelium. Reactive atypical cells involved the surface biliary epithelium and intramural glands and were associated with inflammation and metaplastic changes. The presence of goblet, mucinous, squamous, and reactive atypical cells in association with hyperplasia of intramural glands in frozen sections or small biopsy specimens may be mistaken for malignancy; hence, recognition of these lesions is of diagnostic importance.

Human Pathology, 2015

BAP1 (BRCA1-associated protein 1) is a tumor suppressor gene whose mutations have recently been r... more BAP1 (BRCA1-associated protein 1) is a tumor suppressor gene whose mutations have recently been reported to increase susceptibility for the development of uveal melanoma, cutaneous atypical and epithelioid melanocytic lesions, clear cell renal cell carcinoma, and other tumors. Screening for BAP1 mutation/loss/inactivation and BRAFV600E mutation can be done by immunohistochemistry. We investigated BAP1 and BRAFV600E expression in 193 sporadic melanocytic lesions (11 dermal nevi, 20 congenital nevi, 40 primary and nondesmoplastic melanomas, 40 desmoplastic melanomas, 23 metastatic melanomas, 17 Spitz nevi, 19 atypical Spitz nevi, 8 atypical Spitz tumors, 14 proliferative nodules arising in congenital nevi, 1 nevus during pregnancy) and 30 melanocytic lesions from 3 patients with family history of uveal melanoma and BAP1 germline mutation. Most sporadic melanocytic lesions exhibited positive BAP1 nuclear staining, except for 1 proliferative nodule arising in congenital nevus, 1 desmoplastic, 1 nevoid, and 2 metastatic melanomas. BRAFV600E positivity was demonstrated in 80% of dermal, 5% of congenital, 6% of Spitz, and 5.5% of atypical Spitz nevi; 29% of proliferative nodules arising in congenital nevi; and 24% of primary and nondesmoplastic and 35% of metastatic melanomas. Combined BAP1 loss and BRAFV600E staining was seen in 67% of BAP1 tumor syndrome-associated lesions and in none of the sporadic melanocytic proliferations including Spitz and atypical Spitz nevi and atypical Spitz tumors, with the exception of 1 primary melanoma. The combined BAP1-BRAFV600E+ immunoprofile appears to be a constant feature of BAP1 tumor syndrome-associated melanocytic lesions, and the designation of Spitz nevi or variants thereof appears to be inaccurate for this group of lesions.

Melanocytic Lesions, 2014