Publications by authors named "Tien Anh N Tran"

27 Publications

  • Page 1 of 1

Hyaline Inclusion Acanthoma.

Am J Dermatopathol 2021 Feb 16. Epub 2021 Feb 16.

Department of Pathology, Advent Health Orlando, FL; Department of Pathology and Laboratory Medicine, Dartmouth Hitchcock Medical Center, Lebanon, NH; and Geisel School of Medicine at Dartmouth, Hanover, NH.

Abstract: Eosinophilic hyaline inclusions (EHIs) or globules have been reported in various cutaneous tumors including vascular lesions, myoepithelial neoplasms, and basal cell carcinoma. In basal cell carcinoma, the presence of intracytoplasmic inclusions is reportedly associated with myoepithelial differentiation. In this regard, EHI has not been conclusively documented in a cutaneous lesion of genuine squamous cell lineage without aberrant differentiation. In the current case, a biopsy from the right thigh of a 71-year-old male patient demonstrated a relatively well-demarcated intraepidermal squamous lesion featured an admixture of predominantly enlarged keratinocytes harboring distinct eccentric intracytoplasmic EHI and a smaller population of keratinocytes displaying pale cytoplasm. Cytologic atypia, mitotic activity, and inflammatory cells were not identified. The intracytoplasmic EHI stained red with Masson's trichrome and were negative with periodic-acid Schiff with and without diastase. Immunologically, the lesion was strongly and diffusely positive for various cytokeratins but negative for ubiquitin and myoepithelial markers. Only cytokeratin AE1 revealed a differential staining pattern as the suprabasal lesional cells displayed significantly stronger immunoreactivity in comparison with the adjacent normal keratinocytes. Polymerase chain reaction for low-risk and high-risk human papillomavirus was negative. Molecular studies did not reveal any mutations commonly encountered in seborrheic or lichenoid keratoses. As an analogous lesion has not previously reported in the literature, the term hyaline inclusion acanthoma is proposed for this peculiar lesion.
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http://dx.doi.org/10.1097/DAD.0000000000001927DOI Listing
February 2021

Ciliated and Mucinous Adenomatous Syringometaplasia: The Missing Link of the "Ciliated Eccrine Metaplasia" Theory in the Histogenesis of Cutaneous Eccrine Ciliated Cyst?

Authors:
Tien Anh N Tran

Am J Dermatopathol 2021 Feb 16. Epub 2021 Feb 16.

Department of Pathology, Advent Health Orlando, Orlando, FL.

Abstract: A variety of metaplastic changes has been reported in eccrine ducts and glands with squamous and mucinous syringometaplasia representing the most common histopathologic patterns. In the current case, a previously unreported variant of syringometaplasia was described in a female newborn with a 2-cm occipital cutaneous defect consistent with cutis aplasia. Over a more than 1-year period of local treatment, an enlarging plaque associated with local alopecia developed at the site of the original ulcerated area. A local excision demonstrated a superficial hypertrophic scar associated with a complete loss of hair follicles. In addition, there was a proliferation of eccrine glands and ducts lined by cuboidal epithelial cells arranged in a linear distribution beneath the scar area. Focal anastomosing of the proliferative ducts was identified. In few dilated ducts, the epithelial lining was composed of an inner layer of columnar cells with well-formed apical cilia and intracytoplasmic mucin and an outer layer of myoepithelial cells. The mucinous and ciliated cells were positive for epithelial membranous antigen and carcinoembryonic antigen, but negative for estrogen receptors, progesterone receptors, and thyroid transcription factor-1. Because this variant of eccrine metaplasia has not hitherto been reported in the literature, the term ciliated and mucinous adenomatous syringometaplasia was proposed for this unusual histologic finding. Mucinous and ciliated adenomatous syringometaplasia not only expands the spectrum of metaplastic changes in sweat gland units, but also might represent the missing link in the histogenesis of a subset of cutaneous ciliated cysts.
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http://dx.doi.org/10.1097/DAD.0000000000001924DOI Listing
February 2021

Apocrine (Nodular) Hidradenoma and Adenomyoepithelioma Most Likely Do Not Form a Biological Continuum of Adnexal Neoplasia.

Authors:
Tien Anh N Tran

Am J Dermatopathol 2021 Jun;43(6):471-475

Department of Pathology, Advent Health Orlando, Orlando, FL.

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http://dx.doi.org/10.1097/DAD.0000000000001870DOI Listing
June 2021

Intratubal Pseudopapillary Histiocytic Hyperplasia: A New Histologic Variant in the Spectrum of Histiocytic Lesions Involving the Fallopian Tube.

Int J Gynecol Pathol 2021 Jul;40(4):369-375

Although histiocytic lesions of the fallopian tube are relatively rare compared to their epithelial counterparts, there exists a spectrum of histiocytic lesions involving the fallopian tube that are described under different terminologies dependent on the involved compartment of the fallopian tube. A common histologic denominator of all the hitherto reported tubal histiocytic lesions is the presence of sheets and clusters of histiocytes without any supportive connective tissue. The current study describes three cases of a heretofore-undescribed papillary histiocytic lesion in the lumen of the fallopian tube. All 3 lesions were characterized by avascular, hyaline collagenous papillary cores surrounded by a monotonous population of epithelioid cells, morphologically resembling mesothelial cell hyperplasia, but displaying a histiocytic immunophenotype with diffuse immunopositivity for CD68. Since the papillary cores did not harbor any vasculature, the term intratubal pseudopapillary histiocytic hyperplasia was proposed for this histiocytic proliferation which expands the spectrum of histiocytic lesions of the fallopian tube. Although probably of no clinical significance, practicing pathologists should be aware of this peculiar histiocytic lesion of the fallopian tube to avoid misdiagnosis and unnecessary immunohistochemical testing.
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http://dx.doi.org/10.1097/PGP.0000000000000740DOI Listing
July 2021

Concomitant neuroendocrine tumor and gastrointestinal stromal tumor in a duodenal fine needle aspiration: A cytologic clue for neurofibromatosis type 1.

Diagn Cytopathol 2021 Feb 31;49(2):E45-E48. Epub 2020 Aug 31.

Center of Intervention Endoscopy, Advent Health Orlando, Orlando, Florida, USA.

The identification of two cell populations displaying different cytologic characteristics in the same fine needle aspiration (FNA), one with an epithelioid appearance and the other spindle cell morphology, is an extremely rare phenomenon and potentially represents a source of diagnostic confusion. Depending on the lineage and relationship of the two cell types, the differential diagnosis is broad and encompasses a wide spectrum of entities. The current case describes the presence of nests and clusters of neuroendocrine cells associated with rare spindle cell fragments of gastrointestinal stromal tumor (GIST) in the same fine needle aspiration of a duodenal mass. Our literature analysis revealed that such combined cytologic findings were hitherto never reported and the concurrence of well-differentiated neuroendocrine tumor (NET) and GIST is almost pathognomonic for neurofibromatosis type 1 (NF-1).
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http://dx.doi.org/10.1002/dc.24579DOI Listing
February 2021

Local ALK-Positive Histiocytosis With Unusual Morphology and Novel Gene Fusion.

Int J Surg Pathol 2020 Nov 27:1066896920976862. Epub 2020 Nov 27.

Advent Health Orlando, Orlando, FL, USA.

ALK-positive histiocytosis was first described in 2008 as a systemic histiocytic disorder involving young infants and neonates. Subsequently, cases of local ALK-positive histiocytosis as well as clinical presentation in adult patients have been increasingly reported in the literature. The current case documented the hitherto largest local ALK-positive histiocytosis lesion involving the mesentery of a 20-year-old female patient, a clinical presentation that has not been previously reported in the medical literature. Of note was the presence of numerous lymphocytes, plasma cells, and eosinophils as well as the formation of lymphoid follicles in the lesion, mimicking an inflammatory myofibroblastic tumor. Other unique histologic aspects of the current case included the nested arrangement of the histiocytes, intravascular extension of the histiocytic proliferation into a large vein, and tumor necrosis. Notably, molecular studies revealed a novel (exon 12) (exon 20) gene fusion. Therefore, ALK-positive histiocytosis with gene fusion expands the clinical, histologic, and molecular spectrum of local ALK-positive histiocytosis. Since ALK-positive histiocytosis associated with a significant inflammatory component can pose considerable diagnostic challenges, increased awareness of this peculiar variant of ALK-positive histiocytosis is essential to minimize the risk of misdiagnosis.
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http://dx.doi.org/10.1177/1066896920976862DOI Listing
November 2020

Local PEComatosis of the Appendix: New Insights Into the Histogenesis of Nodular Granular Muscle Degeneration and Granular Cells/Granular Cell Lesions of the Appendix.

Int J Surg Pathol 2020 Dec 18;28(8):899-905. Epub 2020 May 18.

Florida Orlando Hospital, Orlando, FL, USA.

Nodular granular muscle degeneration (NGMD) of the appendix is a rare histologic curiosity characterized by distinctive nests of polygonal epithelioid cells with abundant pale-pink eosinophilic granular cytoplasm, mostly distributed in the inner layer of the muscularis propria or submucosa of the appendix. Although the nature of the cells of interest in NGMD of the appendix has not been completely elucidated, it is believed that they denote degenerative smooth muscle cells of the appendiceal muscularis propria, a histologic finding described as granular cells/granular cell lesions of the appendix in the 1960s. In this article, we described a new case of NGMD of the appendix and documented for the first time that this peculiar lesion actually represents a form of perivascular epithelioid cell proliferation based on its dual immunopositivity for myogenic and melanocytic markers. We also analyzed the old medical literature on granular cells/granular cell lesions of the appendix to shed some light on this ill-defined morphologic finding and its relationship to NGMD of the appendix. Since NGMD of the appendix is a lesion of perivascular epithelioid cells, the term NGMD is a misnomer, and hence, the designation "local PEComatosis of the appendix" is proposed for this unusual phenomenon.
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http://dx.doi.org/10.1177/1066896920922589DOI Listing
December 2020

Primary cutaneous solitary fibrous tumor with entrapped eccrine components.

Authors:
Tien Anh N Tran

J Cutan Pathol 2020 Sep 29;47(9):845-849. Epub 2020 Jun 29.

Department of Pathology, Advent Health Orlando, Orlando, Florida, USA.

First described in the pleura, solitary fibrous tumor (SFT) was subsequently reported in a variety of organ systems. Compared to other anatomic sites, primary cutaneous and superficial SFTs are relatively rare. Although several histopathologic variants of cutaneous and superficial SFT have been described, a primary cutaneous SFT harboring glandular components has not hitherto been documented in the literature. The current case report describes a spindle cell neoplasm of the right finger in a female patient with characteristic morphologic and immunohistochemical features of a SFT. Unexpectedly, various glandular and ductal components were identified in the SFT. A few hyperplastic lobules of sweat glands demonstrating similar morphology as the intratumoral glandular components and composed of secretory coils displaying mucinous metaplasia and ducts were detected in the attached subcutaneous tissue, suggestive of an inductive or obstructive effect of the SFT on the eccrine units. The intratumoral glands and ducts were judged to represent entrapped benign eccrine components from the attached subcutaneous tissue. Since this variant of SFT with entrapped eccrine components could mimic many biphasic epithelial and stromal tumors, pathologists should be aware of this unusual variant of SFT to avoid potential erroneous diagnosis, particularly mistaken confusion with a biphasic synovial sarcoma.
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http://dx.doi.org/10.1111/cup.13717DOI Listing
September 2020

Primary Cutaneous Adenomyoepithelioma Ex Spiradenoma With Malignant Histologic Features, Epithelial-Myoepithelial Carcinoma Type: A First Case Report With Molecular Studies.

Int J Surg Pathol 2020 Jun 9;28(4):427-435. Epub 2019 Dec 9.

Dartmouth-Hitchcock Medical Center, Lebanon, NH, USA.

Adenomyoepithelioma is an extremely rare primary cutaneous neoplasm. Although there is ample evidence on the existence of malignant adenomyoepithelioma in the breast, a malignant counterpart in the skin has not been documented. We report a primary cutaneous adenomyoepithelioma (pcAME) with malignant features arising from a spiradenoma in a 39-year-old female patient. The tumor was solid-cystic in appearance and entirely located in the subcutaneous tissue. Histologically, the tumor displayed foci of adenomatous changes and adenomyoepitheliomatous hyperplasia adjacent to a minute spiradenoma. Gradual increase of architectural complexity, cytologic atypia, mitotic activity, and infiltrative growth were observed in a significant portion of the neoplasm, indicative of transformation to adenomyoepithelioma and subsequently low- to high-grade salivary-type epithelial-myoepithelial carcinoma (EMCA). The intimate dual populations of ductal and myoepithelial cells were highlighted by a panel of immunohistochemical stains in all different components of the tumor. Molecular studies revealed a PIKCA3 mutation, a genetic aberration that has been documented in EMCA, particularly of breast origin. The current case documents for the first time a pcAME with malignant features arising from a spiradenoma and suggests adenomyoepithelioma ex spiradenoma as a possible tumorigenesis pathway of this rare cutaneous tumor.
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http://dx.doi.org/10.1177/1066896919888579DOI Listing
June 2020

BRAF V600E mutations are not an oncogenic driver of solitary xanthogranuloma and reticulohistiocytoma: Testing may be useful in screening for Erdheim-Chester disease.

Exp Mol Pathol 2019 12 19;111:104320. Epub 2019 Oct 19.

Department of Pathology and Laboratory Medicine, Dartmouth-Hitchcock Medical Center, Lebanon, NH, USA; Audrey and Theodor Geisel School of Medicine at Dartmouth, Hanover, NH, USA. Electronic address:

BRAF V600E is the predominant oncogenic driver of L-group histiocytoses, which includes Erdheim-Chester disease (ECD); however, limited data exist on the prevalence of this mutation in sporadic XG family lesions. This study sought to determine the incidence of BRAF V600E mutation in a clinically annotated cohort of patients with xanthogranulomas (XG) and reticulohistiocytomas (RH). A retrospective review of 58 lesions was performed, including 41 XG and 17 RH. Immunohistochemistry (HC) and PCR-based methods were performed to evaluate for the BRAF V600E mutation. The BRAF V600E mutation was detected by IHC/PCR in 3 RH from an adult who had no history of arthritis, malignancy, xanthelasma, diabetes insipidus or bone pain. All other XG and RH were negative for the BRAF V600E mutation. No associated systemic diseases were identified in this cohort. Our findings suggest that BRAF V600E mutations are not an oncogenic driver of sporadic XG and solitary RH. Therefore, identification of such a mutation in a patient with multiple lesions should raise consideration for ECD. We also report the first known BRAF V600E mutation in a patient with multiple reticulohistiocytomas.
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http://dx.doi.org/10.1016/j.yexmp.2019.104320DOI Listing
December 2019

Superficial and Deep Cutaneous Involvement by RAS-Associated Autoimmunne Leukoproliferative Disease (RALD Cutis): A Histologic Mimicker of Histiocytoid Sweet Syndrome.

Am J Dermatopathol 2019 Aug;41(8):606-610

Department of Pathology, Florida Hospital Orlando, Orlando, FL.

RAS-associated autoimmune leukoproliferative disease (RALD) is a recently described noninfectious and nonmalignant clinical syndrome characterized by autoimmune disorders, massive splenomegaly, modest lymphadenopathy, and monocytosis. On the molecular level, RALD is defined by somatic mutations of either NRAS or KRAS gene in a subset of hematopoietic cells. To date, there is a dearth of well-documented histopathologic description of cutaneous involvement by RALD in the literature. In the current case report, a 43-year-old female patient with a history of RALD presented with clinical pictures of sepsis and an erythematous rash in the left lower extremity. Histologic examination revealed a dense perivascular and interstitial infiltrate of immature myeloid cells admixed with scattered neutrophils involving the dermis and subcutaneous adipose tissue, imparting a panniculitis-like histologic pictures. There was a strong angiocentric propensity of the immature hematopoietic cells as well as extensive extravasation of red blood cells, even in the subcutaneous adipose tissue. Immunohistochemically, the immature hematopoietic cells were positive for CD43, CD4, and CD68, but negative for CD34, CD117, and myeloperoxidase. Overall, the histologic and cytologic findings were highly reminiscent of histiocytoid Sweet syndrome. Review of the English literature revealed cutaneous involvements by RALD only in patients with KRAS mutation compared with none of its NRAS counterparts. However, larger clinicopathologic studies on cutaneous involvement by RALD are warranted. The term "RALD cutis" with its histologic and molecular features is suggested to serve as a potential groundwork for future studies of this rare phenomenon.
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http://dx.doi.org/10.1097/DAD.0000000000001332DOI Listing
August 2019

Retroperitoneal Well-Differentiated Liposarcoma With Uterine-Type Leiomyomatous Differentiation: A First Case Report With Literature Analysis of Soft Tissue Sarcomas With Dual Lipomatous and Low-Grade Smooth Muscle Differentiation.

Int J Surg Pathol 2019 Oct 27;27(7):798-803. Epub 2019 May 27.

1 Advent Health Orlando, Orlando, FL, USA.

The occurrence of smooth muscle differentiation in a liposarcoma is a very uncommon phenomenon, even in dedifferentiated liposarcomas. In dedifferentiated liposarcomas, the leiomyosarcomatous component frequently displays high-grade cytologic features, increased mitotic activity, and tumor necrosis. Even more unusual are rare reported cases of low-grade smooth muscle differentiation in atypical lipomatous tumors/well-differentiated liposarcomas (WDLS). The current case describes a 39-year-old female with a large retroperitoneal WDLS harboring a well-demarcated mass composed of benign-appearing smooth muscle fascicles completely lacking cytologic atypia and mitotic activity. In conjunction with the immunopositivity for estrogen and progesterone receptors, the morphology of this nodule was highly reminiscent of a uterine-type leiomyoma. Of note, the lipomatous component largely displayed a lipoma-like appearance with only rare foci of mildly atypical spindle cell proliferation among the adipocytes and few fibrous septae harboring atypical stromal cells. Immunohistochemical and fluorescence in situ hybridization studies revealed gene amplification in both the lipomatous and leiomyoma-like areas, thus confirming the diagnosis of a WDLS with smooth muscle differentiation. A literature review on the subject of sarcomas with dual adipocytic and low-grade smooth muscle differentiation provided sufficient supporting evidence to categorize the tumor as a WDLS with "leiomyomatous" differentiation. Pathologists should be aware of the occurrence of uterine-type leiomyomatous differentiation in retroperitoneal WDLS to avoid potential diagnostic errors.
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http://dx.doi.org/10.1177/1066896919850317DOI Listing
October 2019

Undifferentiated Sarcoma as Intermediate Step in Rhabdomyosarcomatous Transformation of a Metastatic Malignant Melanoma Resistant to Anti-BRAF Therapy: A Phenomenon Associated With Significant Diagnostic and Therapeutic Pitfalls.

Authors:
Tien Anh N Tran

Int J Surg Pathol 2019 Sep 3;27(6):669-677. Epub 2019 Apr 3.

1 Florida Orlando Hospital, Orlando, FL, USA.

Undifferentiated sarcoma has been hypothesized as an intermediate step in the progression of malignant melanoma to rhabdomyosarcoma. The current report describes a new case of rhabdomyosarcomatous transformation in a malignant melanoma and documents the temporal progression of the malignant melanoma to rhabdomyosarcoma in different metastatic sites via undifferentiated sarcoma. A 65-year-old female with a past medical history of malignant melanoma presented with a new lung mass. A core biopsy revealed a malignant spindle cell neoplasm that was negative for all melanocytic markers, suggesting the possibility of a primary pulmonary sarcomatoid carcinoma or sarcoma. The subsequent lobectomy demonstrated an undifferentiated spindle cell neoplasm with areas of rhabdomyoblastic differentiation. Review of the skin lesion and lymph nodes confirmed the diagnosis of the primary cutaneous malignant melanoma, but also revealed that the nodal metastases had largely transformed into an undifferentiated sarcoma with similar morphology as the spindle cell neoplasm in the lung. Molecular studies demonstrated an identical V600E mutation in both the primary malignant melanoma and the lung tumor. Interestingly, the metastatic malignant melanoma with rhabdomyosarcomatous transformation was the single metastasis resistant to anti-BRAF therapy, whereas other metastases displayed dramatic clinical responses. The case report provides further supportive evidence that undifferentiated sarcoma is an intermediate step in the progression of malignant melanoma to rhabdomyosarcoma. Pathologists should be aware of this phenomenon as proper documentation of an undifferentiated sarcoma or newly acquired phenotypic variations in a malignant melanoma could considerably improve diagnostic accuracy and therapeutic management of subsequent recurrences.
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http://dx.doi.org/10.1177/1066896919839143DOI Listing
September 2019

A primary cutaneous vascular neoplasm with histologic features of anastomosing hemangioma.

J Cutan Pathol 2019 May 14;46(5):353-357. Epub 2019 Feb 14.

Departments of Pathology/Microbiology, Pediatrics and Orthopaedic Surgery, Nebraska Medical Center, Omaha, Nebraska.

Anastomosing hemangioma (AH) is a relatively novel variant of benign vascular tumors originally described in the genitourinary tract. Although AH was subsequently documented in various anatomic locations, a primary AH of the skin has not been reported in the literature. The current case report documents a vascular lesion with histologic features reminiscent of an AH. A 41-year-old female patient underwent an excision of a painful nodule on the leg. Histologic examination showed a well-circumscribed vascular lesion composed of anastomosing sinusoidal capillary-sized vessels, several intravascular fibrin thrombi, rare intraluminal nucleated red blood cells, and focal intracytoplasmic hyaline globules. As AH was hitherto only documented in extracutaneous sites, most dermatopathologists are probably not familiar with this variant of hemangioma. The current case report details the morphologic features of a potential example of a primary cutaneous AH to increase the awareness of this distinctive hemangioma variant among dermatopathologists. Larger studies of vascular lesions with similar histologic features and immunohistochemical profiles are warranted to investigate the potential existence of primary AH in the skin.
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http://dx.doi.org/10.1111/cup.13426DOI Listing
May 2019

Psoriasiform, Hyperpigmented Plaques of the Palms and Soles: Answer.

Am J Dermatopathol 2018 Oct;40(10):780-781

Department of Pathology, Albany Medical College, Albany, NY.

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http://dx.doi.org/10.1097/DAD.0000000000000899DOI Listing
October 2018

Undifferentiated Sarcoma as Intermediate Step in the Progression of Malignant Melanoma to Rhabdomyosarcoma: Histologic, Immunohistochemical, and Molecular Studies of a New Case of Malignant Melanoma With Rhabdomyosarcomatous Differentiation.

Am J Dermatopathol 2019 Mar;41(3):221-229

Department of Pathology and Dermatopathology, Albany Medical College, Albany, NY.

Malignant melanoma (MM) may display highly variable phenotypic diversity, sometimes associated with loss of immunohistochemical melanocytic markers and acquisition of nonmelanocytic lineage of differentiation. Primary cutaneous MM with rhabdomyosarcomatous differentiation is extremely rare with only 5 reported cases in the literature. To date, a chronological progression of a MM to rhabdomyosarcoma has not been conclusively documented. A 96-year-old man underwent a re-excision of an "atypical fibroxanthoma" of the forearm, which revealed a small lentigo maligna melanoma associated with a dominant dermal high-grade spindle cell nodule admixed with a population of malignant polygonal epithelioid cells. On immunohistochemical studies, the spindle cells were completely negative for all melanocytic markers, whereas a small population of polygonal neoplastic cells at the periphery was positive for Desmin and Myo-D1, supporting early rhabdomyosarcomatous transformation. Several subsequent re-excisions demonstrated merely nodules of malignant pleomorphic epithelioid cells with rhabdomyosarcomatous differentiation and devoid of melanocytic markers. In addition, both rhabdomyosarcomatous component and original MM displayed identical mutations. Therefore, the histologic, immunohistochemical, and molecular findings documented for the first time a chronological progression from an invasive MM to a pleomorphic rhabdomyosarcoma through an intermediate stage of undifferentiated sarcoma/atypical fibroxanthoma. Interestingly, subsequent recurrences of pure rhabdomyosarcomatous component displayed skip lesions/microsatellitosis, marked tumor-infiltrative lymphocytes, and rare junctional nests of rhabdomyosarcomatous cells in the epidermis, histologic features that were not described in primary cutaneous rhabdomyosarcoma and therefore could serve as morphologic clues to the diagnosis of rhabdomyosarcomatous transformation in an MM.
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http://dx.doi.org/10.1097/DAD.0000000000001236DOI Listing
March 2019

Psoriasiform, Hyperpigmented Plaques of the Palms and Soles: Challenge.

Am J Dermatopathol 2018 Oct;40(10):e132-e133

Department of Pathology, Albany Medical College, Albany, NY.

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http://dx.doi.org/10.1097/DAD.0000000000000900DOI Listing
October 2018

Detection of BRAF mutation in the cytocentrifugation supernatant fluid from fine-needle aspiration of thyroid lesions may enhance the diagnostic yield.

Cytojournal 2017 24;14. Epub 2017 Feb 24.

Address: Department of Pathology University of Central Florida College of Medicine, Orlando, FL, USA; Department of Pathology and Laboratory Medicine, Florida Hospital, Orlando, FL, USA.

Objective: BRAF mutations using cellular DNA from fine-needle aspiration (FNA) specimens are commonly used to support the diagnosis of papillary thyroid carcinoma (PTC). The goal of this study was to preliminarily evaluate the diagnostic utility of detecting BRAF mutations in the routinely discarded FNA specimen supernatant fluid.

Materials And Methods: Seventy-eight FNAs of thyroid lesions were evaluated for BRAF mutations using both cellular and supernatant DNA. BRAF mutation data were correlated with cytology and surgical pathology.

Results: Of the 78 samples evaluated, 68 (87%) had amplifiable DNA in the supernatant with 2 (3%) positive for BRAF mutations. These two samples showed no mutations in the cellular counterpart. Among the 11 samples showing morphologic findings (FNA/surgical pathology) suspicious/diagnostic of PTC, 6 (55%) samples (one supernatant and five cellulars) were positive for BRAF mutations. This suggests that testing supernatant DNA in FNA specimens may increase the diagnostic yield by 1/11 (9%) in this setting.

Conclusions: The vast majority of routinely discarded FNA supernatants contain amplifiable DNA. In addition, profiling the mutations of BRAF and other genes using supernatant DNA may provide valuable diagnostic information to assist the diagnosis of PTC in patients with clinical/morphologic findings suspicious for malignancies and cellular DNA showing no mutations.
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http://dx.doi.org/10.4103/1742-6413.200935DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5348989PMC
February 2017

Intralymphatic Histiocytosis of the Appendix and Fallopian Tube Associated With Primary Peritoneal High-Grade, Poorly Differentiated Adenocarcinoma of Müllerian Origin.

Int J Surg Pathol 2017 Jun 23;25(4):357-364. Epub 2017 Jan 23.

3 Albany Medical College, Albany, NY, USA.

Intralymphatic histiocytosis (ILH) is a peculiar pathological process characterized by the collections of benign histiocytes in dilated lymph vessels. Although the majority of ILH patients present clinically with various forms of cutaneous manifestation, rare extracutaneous incidences have been reported in the literature. To date, ILH has not been described in an internal visceral organ. We report the case of a 68-year-old woman who underwent an appendectomy during a surgical procedure for a primary peritoneal high-grade, poorly differentiated adenocarcinoma of Müllerian origin. Although no malignancy was identified in the appendix, the appendiceal mucosa and submucosa were expanded by dilated vascular channels harboring aggregates of uniform epithelioid cells. Similar histological changes were also identified in the right fallopian tube. Immunohistochemical studies revealed the lymphatic nature of the vessels and the histiocytic origin of the intravascular cells. Of note was the presence of scattered multinucleated giant cells in the histiocytic population, a histological feature not described hitherto in ILH. To the best of the authors' knowledge, this is the first case of ILH harboring multinucleated giant cells, involving internal visceral organs, and associated with a malignant tumor of the gynecological system. As such, the current case report expands the clinical and histological spectrum of ILH.
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http://dx.doi.org/10.1177/1066896916688307DOI Listing
June 2017

The "Endothelialized Muscularis Mucosae": A Case Report Describing a Large Cavernous Hemangioma at the Terminal Ileum and a New Histologic Clue for Preoperative Diagnosis from Endoscopic Biopsy.

Case Rep Gastrointest Med 2015 9;2015:454836. Epub 2015 Sep 9.

Department of Pathology, Florida Hospital Orlando, 601 E. Rollins Street, Orlando, FL 32803, USA.

Cavernous hemangiomas of the gastrointestinal tract are quite rare and, until now, have been difficult to diagnose preoperatively due their nonspecific presentations and imaging features, as well as a lack of histologic description pertaining to small superficial biopsies such as those obtained endoscopically. We report a unique case of a 4 cm transmural cavernous hemangioma in the terminal ileum with literature review and describe a new histologic finding-the "endothelialized muscularis mucosae," which was discovered upon review of the endoscopic biopsy and could potentially facilitate preoperative diagnosis of these lesions from endoscopic biopsies in the future. These lesions have classically required surgical resection in order to make a definitive diagnosis and rule out malignancy, with which they share many historical and radiographic features. Due to their potential to cause bowel obstruction, intussusception, perforation, and hemorrhage, these lesions may ultimately require surgical resection to relieve symptoms or prevent or treat complications-however, surgical planning and patient counseling could be greatly improved by a preoperative diagnosis. Therefore, gastroenterologists, pathologists, and surgeons should be aware of the "endothelialized muscularis mucosae" which can be very helpful in diagnosing GI cavernous hemangiomas from endoscopic biopsies.
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http://dx.doi.org/10.1155/2015/454836DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4579299PMC
October 2015

Dedifferentiated salivary hybrid carcinoma of the maxillary sinus with pagetoid spread to the overlying lining mucosa.

Head Neck Pathol 2015 Jun 2;9(2):293-9. Epub 2014 Sep 2.

Department of Pathology, Florida Orlando Hospital, 601 East Rollins St., Orlando, FL, 32803, USA,

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http://dx.doi.org/10.1007/s12105-014-0564-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4424200PMC
June 2015

The spectrum of grossly visible pigmented lesions in the uterine cervix: a prospective study.

Int J Gynecol Pathol 2014 Jan;33(1):89-99

Department of Pathology (T.A.N.T., C.A.T., H.V.T.), Florida Orlando Hospital, St Orlando, Florida Department of Pathology (G.N., J.S.R., J.A.C.), Albany Medical College, Albany, New York.

Pigmented lesions of the uterine cervix (UC) have not been systematically studied in the literature. Over an 18-mo period, we prospectively investigated the histologic spectrum of all macroscopically visible pigmented lesions of the UC. The incidence of pigmented UC was 1.6% (33/2118). Histologic examination revealed 32 cases (97%) with a histologic correlate, of which 26 lesions were of melanocytic nature including 25 blue nevi (BNs) (81%) and 1 melanotic macule (3%). The nonmelanocytic lesions included 1 case of focal granulomatous vasculitis (3%), 2 biopsy site-associated reactive changes with hemosiderin-laden macrophages (6.4%), 1 case of hemorrhagic Nabothian cyst (3%), 1 hemangioma (3%), and 1 case of multinucleated giant cell reaction to dark black carbon-like material (3%). Women with UC BN (1.2% incidence) were mostly whites (13/25, 52%) with a mean age of 47.4 yr (range, 31-64 yr). The number and size of BN per UC, all located in the endocervix, varied between 1 to 3 and 0.1 to 2 cm (mean, 0.68 cm). UC BN exhibited 3 distinct morphologic patterns: (1) stromal melanocytic focus composed of fine spindle cells (9/25, 36%); (2) mixed pattern with fine spindle, plump spindle, and epithelioid cells (15/25, 60%); and (3) nevoid stage with epithelioid cells (1/25, 4%). In contrast, cervical melanotic macule was located in the squamous epithelium of the ectocervix and characterized by hyperpigmentation of the basal keratinocytes admixed with scattered slightly enlarged melanocytes. In conclusion, pigmented lesions of the UC are not as uncommon as reported and mostly benign in nature. Several cases may require deeper levels for their detection and to exclude the rare phenomenon of UC melanoma.
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http://dx.doi.org/10.1097/PGP.0b013e31827c6343DOI Listing
January 2014

Does a uterine manipulator affect cervical cancer pathology or identification of lymphovascular space involvement?

Gynecol Oncol 2012 Oct 16;127(1):98-101. Epub 2012 Jul 16.

Florida Hospital Gynecologic Oncology, Florida Hospital Cancer Institute, Orlando, FL 32804, USA.

Objective: Uterine manipulators are a useful adjunct for robotic-assisted radical hysterectomy (RARH), but some surgeons avoid their use for fear of altering pathology or interpretation of lymphovascular space involvement (LVSI). We retrospectively compared clinico-pathological data and tumor pathology from patients with cervical cancer operated by laparotomy vs. RARH.

Methods: Charts from cervical cancer patients who underwent radical hysterectomy from January-1997 to June-2010 were reviewed for tumor histology, grade, FIGO stage, lymph node status, LVSI, depth of invasion, and tumor size. A ConMed V-Care® uterine manipulator was used in all robotic cases. H&E stained slides from 20 robotic and 24 open stage IB1 cases with LVSI reported in the original pathology were re-reviewed by a blinded pathologist for analysis of tissue artifacts and LVSI.

Results: Two-hundred-thirty-six cases (185 open, 51 robotic) with stages IA2, IB1 and IB2 cervical cancer were reviewed. No significant differences in histology (squamous cell carcinoma, 65% vs. 51%; p=0.1), IB1 lesion size (≤2 cm, 62% vs. 61%, p>0.1), LVSI (34% vs. 39%, p>0.1), and depth of stromal invasion (p>0.1) was found between open and robotic groups. Histologic examination of all IB1 cervical carcinomas revealed a higher degree of surface disruption [45% (9/20) vs. 12.6% (3/24), p=0.038] and artifactual "parametrial carryover" [65% (13/20) vs. 29% (7/24), p=0.037] in robotic vs. open groups, respectively, but no significant differences in the rate of LVSI.

Conclusion: RARH cases that utilized a uterine manipulator did not show any clinico-pathological differences in depth of invasion, LVSI, or parametrial involvement compared to open cases.
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http://dx.doi.org/10.1016/j.ygyno.2012.07.094DOI Listing
October 2012

Metastatic appendiceal mucinous adenocarcinoma to well-differentiated diffuse mesothelioma of the peritoneal cavity: a mimicker of florid mesothelial hyperplasia in association with neoplasms.

Int J Gynecol Pathol 2008 Oct;27(4):526-30

Department of Pathology, Florida Hospital Orlando, Orlando, Florida 32803, USA.

Atypical/florid mesothelial hyperplasia associated with another neoplastic process is not an infrequent phenomenon and has been reported in a variety of tumors. In those instances, the mesothelial proliferation might create a misdiagnosis of metastatic carcinoma but seldom raises the possibility of a well-differentiated mesothelioma seeded by metastatic neoplastic cells. Herein, we report the case of a 40-year-old woman originally diagnosed with exuberant atypical mesothelial hyperplasia after an diagnostic laparoscopy. The subsequent operation, however, demonstrated a mucinous neoplasm of the appendix with involvement of the peritoneal cavity in the form of peritoneal mucinous carcinomatosis as well as metastases to the uterine serosa and adnexal surfaces. Microscopic analysis revealed an appendiceal adenocarcinoma with signet-ring-cell features that has metastasized to a diffuse well-differentiated mesothelioma of the peritoneal cavity. In many areas, the atypical mesothelial proliferation is indistinguishable from florid mesothelial hyperplasia. The true nature of the mesothelial proliferation was only confirmed after extensive additional sampling, which showed unequivocal stromal invasion. To the best of our knowledge, this is the first report of a metastatic appendiceal mucinous adenocarcinoma to a well-differentiated diffuse mesothelioma of the peritoneal cavity. Although commonly associated with atypical/ florid mesothelial hyperplasia, a carcinoma can rarely metastasize to a well-differentiated mesothelioma, which can pose significant diagnostic difficulties because it can mimic a reactive process. This unusual case report expands the spectrum of mesothelial proliferation in conjunction with a malignant neoplasm and serves to remind pathologists that such a concomitant occurrence exists.
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http://dx.doi.org/10.1097/PGP.0b013e3181705792DOI Listing
October 2008

Alpha-fetoprotein-producing serous carcinoma of the uterus metastasizing to the ovaries, mimicking primary ovarian yolk sac tumor: a case report and review of the literature.

Int J Gynecol Pathol 2007 Jan;26(1):66-70

Department of Pathology, Florida Hospital Orlando, Orlando, Florida, USA.

In the uterus, most alpha-fetoprotein (AFP) producing neoplasms belong to the categories of malignant mixed muellerian tumor, hepatoid carcinoma, and yolk sac tumor. We describe the case of a 44-year-old woman who presented with vaginal bleeding, pelvic mass, and preoperative elevated AFP serum level, clinically suggestive of a primary ovarian yolk sac tumor. However, histological examination revealed a uterine AFP-producing papillary serous carcinoma, which has metastasized to the ovaries. Upon review of the literature on primary endometrial neoplasms with AFP production, 2 categories with possibly different histogenesis and biological behavior become evident: the primary yolk sac tumor of the uterus in young patients (range, 24-49 years; mean, 34 years) and the common high grade endometrial carcinoma with yolk sac dedifferentiation or aberrant AFP production in elderly patients (range, 55-69 years; mean, 63.7 years). In addition to being only the second case of uterine AFP-producing papillary serous carcinoma, this case is unusual for its clinical and radiological presentation as well as the relatively young age of the patient.
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http://dx.doi.org/10.1097/01.pgp.0000225843.21503.30DOI Listing
January 2007