Bio

Clinical Focus


  • Cancer- cutaneous oncology
  • Cancer > Cutaneous (Dermatologic) Oncology
  • Anatomic Pathology
  • Dermatopathology
  • Melanocytic neoplasia

Academic Appointments


Administrative Appointments


  • Fellowship Program Director, Dermatopathology (2012 - Present)
  • Director, Dermatopathology (2011 - Present)
  • Associate Director, Dermatopathology (2009 - 2011)

Honors & Awards


  • 1st Place Award: Oral Abstract Competition (Charay Jennings), ASDP (2011)
  • 1st Place Award: Oral Abstract Competition (Salma Dabiri), ASDP (2010)
  • 2nd Place Award: Duel in Dermatopathology Oral Abstract Competition (Salma Dabiri), ASDP (2009)
  • 1st Place Award: Oral Abstract Competition, ASDP (2007)
  • 1st Place Award: Duel in Dermatopathology Abstract Competition, ASDP (2005)

Professional Education


  • Fellowship:Yale University School of Medicine (2008) CT
  • Residency:Yale New Haven Hospital (2007) CT
  • Residency:Yale New Haven Hospital (2004) CT
  • Board Certification: Dermatopathology, American Board of Pathology (2008)
  • Board Certification: Anatomic Pathology, American Board of Pathology (2007)
  • Internship:Yale New Haven Hospital (2001) CT
  • Medical Education:Mount Sinai Medical Center (2000) NY

Research & Scholarship

Clinical Trials


  • Pralatrexate and Bexarotene in Patients With Relapsed or Refractory Cutaneous T-cell Lymphoma Not Recruiting

    This study is designed to determine the recommended dose, safety, pharmacokinetics, and early efficacy of the combination of pralatrexate plus oral bexarotene in patients with relapsed or refractory CTCL.

    Stanford is currently not accepting patients for this trial. For more information, please contact Cutaneous Lymphoma Coordinator, (650) 421 - 6370.

    View full details

  • Analysis of Cutaneous and Hematologic Disorders by High-Throughput Nucleic Acid Sequencing Recruiting

    The goal of this study is to identify genetic changes associated with the initiation, progression, and treatment response of response of cutaneous and hematologic disorders using recently developed high-throughput sequencing technologies. The improved understanding of the genetic changes associated with cutaneous and hematologic disorders may lead to improved diagnostic, prognostic and therapeutic options for these disorders.

    View full details

Teaching

2013-14 Courses


Publications

Journal Articles


  • Multiple Eruptive Pilomatricomas in a 9-year-Old Boy with Glioblastoma. Pediatric dermatology Hollmig, S. T., Tollefson, M. M., Kim, J., Khuu, P. 2013; 30 (6): 756-758

    Abstract

      A 9-year-old male presented to our dermatology clinic with a recent history of developing numerous cutaneous pilomatricomas, and was subsequently discovered to have sustained a recurrence of his glioblastoma multiforme. Immunohistochemical staining of a representative pilomatricoma and his original brain tumor revealed upregulation and nuclear localization of beta-catenin, a sign associated with poor prognosis in glioblastoma. We hypothesize that the development of multiple pilomatricomas may have been a hallmark of this patient's tumor recurrence and provide support for a recent report of an association between multiple pilomatricomas and gliomatosis cerebri.

    View details for DOI 10.1111/j.1525-1470.2011.01714.x

    View details for PubMedID 22304393

  • Activating HRAS Mutation in Agminated Spitz Nevi Arising in a Nevus Spilus. JAMA dermatology Sarin, K. Y., Sun, B. K., Bangs, C. D., Cherry, A., Swetter, S. M., Kim, J., Khavari, P. A. 2013; 149 (9): 1077-1081

    Abstract

    IMPORTANCE Spitz nevi are benign melanocytic proliferations that can sometimes be clinically and histopathologically difficult to distinguish from melanoma. Agminated Spitz nevi have been reported to arise spontaneously, in association with an underlying nevus spilus, or after radiation or chemotherapy. However, to our knowledge, the genetic mechanism for this eruption has not been described. OBSERVATIONS We report a case of agminated Spitz nevi arising in a nevus spilus and use exome sequencing to identify a clonal activating point mutation in HRAS (GenBank 3265) (c.37G→C) in the Spitz nevi and underlying nevus spilus. We also identify a secondary copy number increase involving HRAS on chromosome 11p, which occurs during the development of the Spitz nevi. CONCLUSIONS AND RELEVANCE Our results reveal an activating HRAS mutation in a nevus spilus that predisposes to the formation of Spitz nevi. In addition, we demonstrate a copy number increase in HRAS as a "second hit" during the formation of agminated Spitz nevi, which suggests that both multiple Spitz nevi and solitary Spitz nevi may arise through similar molecular pathways. In addition, we describe a unique investigative approach for the discovery of genetic alterations in Spitz nevi.

    View details for DOI 10.1001/jamadermatol.2013.4745

    View details for PubMedID 23884457

  • Intravascular ALK-negative Anaplastic Large Cell Lymphoma With Localized Cutaneous Involvement and an Indolent Clinical Course Toward Recognition of a Distinct Clinicopathologic Entity AMERICAN JOURNAL OF SURGICAL PATHOLOGY Metcalf, R. A., Bashey, S., Wysong, A., Kim, J., Kim, Y. H., Gratzinger, D. 2013; 37 (4): 617-623

    Abstract

    Intravascular large T-cell or NK-cell lymphomas rarely present with cutaneous involvement. Intravascular cytotoxic T or NK lymphomas presenting in the skin (cIT/NKL) are often EBV, and reported cases follow a highly aggressive clinical course. Intravascular anaplastic large cell lymphoma (ALCL) by contrast is extraordinarily rare and, when it presents in the skin, raises the question of aggressive clinical behavior in the manner of cIT/NKL versus indolent clinical behavior in the manner of primary cutaneous ALCL. Here we describe a case of localized cutaneous intravascular anaplastic lymphoma kinase-negative ALCL (cIALCL) with a very indolent clinical course. The patient experienced a single cutaneous relapse and remains alive without disease 4 years after diagnosis. Review of the literature reveals multiple clinicopathologic differences between cIALCL and cIT/NKL: distribution (cIALCL, single skin region, P=0.021, Fisher exact test); histology (cIALCL, cohesive with necrosis, P=0.005); immunophenotype (cIALCL, strongly CD30, P=0.021; cIT/NKL, CD56 and/or EBV, P=0.003); and indolent clinical behavior with a trend toward better overall survival (P=0.067, Kaplan-Meier survival analysis). Our index case of cIALCL and 1 other tested case were immunohistochemically confirmed to be intralymphatic (contained within D2-40+vessels) as compared with the blood vessel localization of cIT/NKL. Recognition of cIALCLs as a distinct clinicopathologic entity, and in particular their distinction from aggressive, usually EBV cIT/NKLs, may be possible on the basis of a combination of clinicopathologic criteria, allowing for localized therapy in a subset of patients.

    View details for DOI 10.1097/PAS.0b013e318280aa9c

    View details for Web of Science ID 000316184000019

    View details for PubMedID 23480896

  • Mosaic Activating RAS Mutations in Nevus Sebaceus and Nevus Sebaceus Syndrome JOURNAL OF INVESTIGATIVE DERMATOLOGY Sun, B. K., Saggini, A., Sarin, K. Y., Kim, J., Benjamin, L., LeBoit, P. E., Khavari, P. A. 2013; 133 (3): 824-827

    View details for DOI 10.1038/jid.2012.377

    View details for Web of Science ID 000315008500032

    View details for PubMedID 23096709

  • Is Tanning Bed Exposure Associated With Aggressive Basal Cell Carcinoma? JOURNAL OF CLINICAL ONCOLOGY Gamba, C. A., Wysong, A., Million, L., Aasi, S., Kim, J., Tang, J. Y. 2012; 30 (32): E333-E336

    View details for DOI 10.1200/JCO.2012.42.1008

    View details for Web of Science ID 000310914800006

    View details for PubMedID 23008324

  • Sox10 is expressed in primary melanocytic neoplasms of various histologies but not in fibrohistiocytic proliferations and histiocytoses JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY Shin, J., Vincent, J. G., Cuda, J. D., Xu, H., Kang, S., Kim, J., Taube, J. M. 2012; 67 (4): 717-726

    Abstract

    Sox10 is a transcription factor associated with neural crest development. Its expression has been reported in melanocytes and peripheral nerve sheath cells and their associated tumors.To assess Sox10 sensitivity in benign and malignant melanocytic neoplasms of various histologic subtypes and to discern the specificity of Sox10 in distinguishing between melanocytic neoplasms and fibrohistiocytic and histiocytic mimickers.Sox10 expression was examined by immunohistochemistry in 145 cases of formalin-fixed paraffin-embedded tissue, including benign and malignant melanocytic lesions of various histologies and stages (n = 83), fibrohistiocytic and histiocytic lesions (n = 33), and peripheral nerve sheath tumors (n = 19), among others (n = 10).Immunoreactivity with Sox10 was observed in 100% (83/83) of benign and malignant melanocytic lesions of various subtypes, as well as in 100% (19/19) of benign and malignant peripheral nerve sheath lesions. Among the fibrohistiocytic proliferations and histiocytoses examined, Sox10 was negative in all cases (0/33). Sox10 expression did not vary by histologic subtype in nevi or melanoma; however, both the percentage of tumor nuclei demonstrating Sox10 expression and the intensity of expression were inversely correlated with malignant potential (nevi, melanoma in situ, invasive and metastatic melanoma) (P < .001, P = .016, respectively). Malignant peripheral nerve sheath tumors also showed decreased mean Sox10 expression and decreased intensity of expression when compared with benign counterparts (P < .001, P = .021, respectively).This is a retrospective study with 145 cases included.Sox10 is a highly sensitive marker for melanocytic proliferations and may be useful diagnostically when the differential diagnosis includes fibrohistiocytic and histiocytic proliferations demonstrating S100 expression.

    View details for DOI 10.1016/j.jaad.2011.12.035

    View details for Web of Science ID 000309160200057

    View details for PubMedID 22325460

  • Spindle Cell Neoplasms Encountered in Dermatologic Surgery: A Review DERMATOLOGIC SURGERY Hollmig, S. T., Sachdev, R., Cockerell, C. J., Posten, W., Chiang, M., Kim, J. 2012; 38 (6): 825-850

    Abstract

    Cutaneous spindle cell tumors share the common feature of appearing as spindle-shaped cells on light microscopy. Their pathogenesis, presentation, and prognosis are highly variable, and numerous techniques for workup and treatment have been reported. We performed an analysis of the available scientific literature in order to codify the clinical, immunohistochemical, and biologic features of these tumors and to provide insight into the most effective practices for their management, with a focus on Mohs micrographic surgery (MMS). In this article, the clinical and histopathological characteristics of dermatofibrosarcoma protuberans, atypical fibroxanthoma, malignant fibrous histiocytoma, spindle cell squamous cell carcinoma, superficial leiomyosarcoma, desmoplastic melanoma, cutaneous angiosarcoma, and myofibrosarcoma are described, and methods for diagnosis, workup, treatment, and surveillance are evaluated. Cutaneous spindle cell neoplasms are diverse in origin, presentation, and behavior. Immunostaining assists in differentiating among the various types. Further workup is sometimes indicated to characterize local invasion or assess for metastatic disease. Surgery is typically the first-line treatment, and MMS is associated with low recurrence rates and a tissue-sparing advantage for many tumors. Adjuvant treatments, including radiation therapy, molecular-targeted therapy, and conventional chemotherapy, are sometimes indicated, and close clinical surveillance is required after treatment.

    View details for DOI 10.1111/j.1524-4725.2012.02296.x

    View details for Web of Science ID 000304528100001

    View details for PubMedID 22268379

  • Abdominal Mass, Anemia, Diabetes Mellitus, and Necrolytic Migratory Erythema DIGESTIVE DISEASES AND SCIENCES Qadan, M., Visser, B., Kim, J., Pai, R., Triadafilopoulos, G. 2012; 57 (6): 1465-1468

    View details for DOI 10.1007/s10620-011-1967-5

    View details for Web of Science ID 000304396700007

    View details for PubMedID 22089253

  • Primary Cilium Depletion Typifies Cutaneous Melanoma In Situ and Malignant Melanoma PLOS ONE Kim, J., Dabiri, S., Seeley, E. S. 2011; 6 (11)

    Abstract

    Cutaneous melanoma is a lethal malignancy that arises spontaneously or via in situ precursor neoplasms. While melanoma in situ and locally invasive malignant melanoma can be cured surgically, these lesions can sometimes be difficult to distinguish from melanocytic nevi. Thus, the identification of histolopathologic or molecular features that distinguish these biologically distinct lesions would represent an important advance. To this end, we determined the abundance of melanocytic primary cilia in a series of 62 cases composed of typical cutaneous melanocytic nevi, melanoma in situ, invasive melanoma, and metastatic melanoma. Primary cilia are sensory organelles that modulate developmental and adaptive signaling and notably, are substantially depleted from the neoplastic epithelium of pancreatic carcinoma at a stage equivalent to melanoma in situ. In this series, we find that while nearly all melanocytes in 22 melanocytic nevi possessed a primary cilium, a near-complete loss of this organelle was observed in 16 cases of melanoma in situ, in 16 unequivocal primary invasive melanomas, and in 8 metastatic tumors, each associated with a cutaneous primary lesion. These findings suggest that the primary cilium may be used to segregate cutaneous invasive melanoma and melanoma in situ from melanocytic nevi. Moreover, they place the loss of an organelle known to regulate oncogenic signaling at an early stage of melanoma development.

    View details for DOI 10.1371/journal.pone.0027410

    View details for Web of Science ID 000297553900042

    View details for PubMedID 22096570

  • Early pancreatic panniculitis associated with HELLP syndrome and acute fatty liver of pregnancy JOURNAL OF CUTANEOUS PATHOLOGY Kirkland, E. B., Sachdev, R., Kim, J., Peng, D. 2011; 38 (10): 814-817

    Abstract

    Pancreatic panniculitis represents a rare cutaneous disorder most commonly associated with acute or chronic pancreatitis or pancreatic carcinoma. We describe a case of a 17-year-old woman who presented with a 2-day history of erythematous patches involving her bilateral knees and tender, scattered red-brown nodules involving her bilateral anterior shins. She was seen during a hospitalization for emergent cesarean section and her hospital course was complicated by HELLP syndrome (defined by the presence of hemolysis, elevated liver enzymes, low platelet count), acute fatty liver of pregnancy and pancreatitis. The characteristic histopathologic findings, including ghost cells, fat necrosis and granular basophilic material with dystrophic calcification, appear in later lesions. In early lesions, as was shown in this case, a neutrophilic subcutaneous infiltrate raises a differential diagnosis including infection, subcutaneous Sweet's syndrome or atypical erythema nodosum. To our knowledge, this represents the first report of pancreatic panniculitis in association with HELLP syndrome and acute fatty liver of pregnancy. Early recognition is critical, as skin lesions may precede the development of pancreatitis. Often, as in our case, the effects of pancreatitis may be life threatening.

    View details for DOI 10.1111/j.1600-0560.2011.01742.x

    View details for Web of Science ID 000294567000010

    View details for PubMedID 21752052

  • Quantitative comparison of MiTF, Melan-A, HMB-45 and Mel-5 in solar lentigines and melanoma in situ JOURNAL OF CUTANEOUS PATHOLOGY Kim, J., Taube, J. M., McCalmont, T. H., Glusac, E. J. 2011; 38 (10): 775-779

    Abstract

    It is often challenging to reliably assess the number of lesional melanocytes in intraepidermal melanocytic proliferations involving sun-damaged skin. Therefore, dermatopathologists routinely use immunostains to help differentiate melanocytes from surrounding keratinocytes.Forty-three cases of solar lentigo or melanoma in situ (of the lentigo maligna type) were retrospectively chosen (20 melanomas in situ and 23 solar lentigo). Microphthalmia transcription factor (MiTF), HMB-45, Melan-A and Mel-5 immunostains were performed with an Azure blue counterstain, and the mean melanocyte counts were calculated within a 1-mm segment of epidermis.In solar lentigines, the mean melanocyte counts were 27 (MiTF), 23 (HMB-45 and Mel-5) and 41 (Melan-A), as compared to hematoxylin and eosin (H&E) (25). In melanoma in situ, the mean melanocyte counts were 112 (MiTF), 149 (Melan-A), 111 (HMB-45) and 80 (Mel-5), as compared to H&E (109).These results show that Melan-A significantly overestimates the density of melanocytes within dermatoheliotic skin. Compared to other tested stains, nuclear staining MiTF allowed greater distinction of melanocytes from keratinocytes with melanized cytoplasm. These findings indicate that MiTF is a superior marker for quantification of melanocytes in the evaluation of subtle intraepidermal melanocytic proliferations and in the differential diagnosis of solar lentigo.

    View details for DOI 10.1111/j.1600-0560.2011.01763.x

    View details for Web of Science ID 000294567000004

    View details for PubMedID 21797920

  • Subcutaneous Nodules in an Elderly Patient Necrobiotic xanthogranuloma ARCHIVES OF DERMATOLOGY Fu, T., Zwerner, J., Kim, J., Tang, J. 2011; 147 (10): 1215-1220

    View details for Web of Science ID 000295944300022

    View details for PubMedID 22006142

  • T(H)1, T(H)2, and T(H)17 cells instruct monocytes to differentiate into specialized dendritic cell subsets BLOOD Alonso, M. N., Wong, M. T., Zhang, A. L., Winer, D., Suhoski, M. M., Tolentino, L. L., Gaitan, J., Davidson, M. G., Kung, T. H., Galel, D. M., Nadeau, K. C., Kim, J., Utz, P. J., Soederstroem, K., Engleman, E. G. 2011; 118 (12): 3311-3320

    Abstract

    Monocytes and T helper (T(H)) cells rapidly infiltrate inflamed tissues where monocytes differentiate into inflammatory dendritic cells (DCs) through undefined mechanisms. Our studies indicate that T(H) cells frequently interact with monocytes in inflamed skin and elicit the differentiation of specialized DC subsets characteristic of these lesions. In psoriasis lesions, T(H)1 and T(H)17 cells interact with monocytes and instruct these cells to differentiate into T(H)1- and T(H)17-promoting DCs, respectively. Correspondingly, in acute atopic dermatitis, T(H)2 cells interact with monocytes and elicit the formation of T(H)2-promoting DCs. DC formation requires GM-CSF and cell contact, whereas T(H) subset specific cytokines dictate DC function and the expression of DC subset specific surface molecules. Moreover, the phenotypes of T cell-induced DC subsets are maintained after subsequent stimulation with a panel of TLR agonists, suggesting that T(H)-derived signals outweigh downstream TLR signals in their influence on DC function. These findings indicate that T(H) cells govern the formation and function of specialized DC subsets.

    View details for DOI 10.1182/blood-2011-03-341065

    View details for Web of Science ID 000295120900018

    View details for PubMedID 21813450

  • The frequency of dual TCR-PCR clonality in granulomatous disorders JOURNAL OF CUTANEOUS PATHOLOGY Dabiri, S., Morales, A., Ma, L., Sundram, U., Kim, Y. H., Arber, D. A., Kim, J. 2011; 38 (9): 704-709

    Abstract

    A granulomatous infiltrate in association with cutaneous T-cell lymphoma is uncommon. The diagnosis of mycosis fungoides can be difficult in the setting of an exuberant granulomatous infiltrate that obscures the neoplastic lymphoid infiltrate, thereby mimicking a granulomatous dermatitis. Therefore, the clinical context and supplemental molecular analysis, such as the demonstration of a monoclonal T-cell population, may assist in diagnosis. Monoclonal T-cell populations have been reported in association with inflammatory conditions and serve as a diagnostic pitfall. The frequency of T-cell clonality in association with granulomatous dermatitides has not yet been established.We identified 29 patients with granulomatous dermatitis who had biopsies at two distinct body sites. Results were correlated with clinical follow up and with clonal T-cell receptor-gamma chain rearrangement as detected by polymerase chain reaction-based analysis (dual TCR-PCR).Clinical follow up was obtained in 17 of 29 cases (58.6%). Twenty-five of 29 cases of granulomatous dermatitis lacked T-cell monoclonality. Three cases of granuloma annulare contained a T-cell clone in one of the two biopsies. One case of necrobiotic xanthogranuloma showed an identical T-cell clone in multiple biopsies.The use of dual TCR-PCR analysis, that is, T-cell clonality analysis in biopsy specimens from two different sites, serves as an adjunct to assist in distinguishing granulomatous inflammatory reactions from granulomatous T-cell lymphoma, including granulomatous mycosis fungoides. The occasional finding of a T-cell clone in a granulomatous dermatitis underscores the importance of clinicopathological correlation in daily diagnosis.

    View details for DOI 10.1111/j.1600-0560.2011.01727.x

    View details for Web of Science ID 000293177000005

    View details for PubMedID 21645036

  • Identification of Nodal Metastases in Melanoma Using Sox-10 AMERICAN JOURNAL OF DERMATOPATHOLOGY Jennings, C., Kim, J. 2011; 33 (5): 474-482

    Abstract

    The presence of S100-positive dendritic cells hinders the identification of isolated melanoma tumor cells and micrometastases in sentinel lymph nodes. Sox-10, a transcription factor that plays an important role in schwannian and melanocytic cell development, is not expressed in dendritic cells. We investigated the diagnostic utility of Sox-10 in the identification of metastases in sentinel and nonsentinel lymph nodes for melanoma. We examined the expression pattern of Sox-10, as compared with S100, Melan-A, and HMB-45 in 93 lymph nodes (40 originally reported as positive and 53 originally reported as negative for metastasis) from 33 sentinel lymph node biopsies and regional lymphadenectomies. Sox-10 and S100 both highlighted metastases in 43 of 43 (100%) positive lymph nodes identified in this study; however, Sox-10 immunohistochemical staining significantly improved the detection of nodal metastases. The nuclear staining of Sox-10 promoted improved distinction between heavily pigmented melanophages and melanocytic metastases in 3 positive lymph nodes. In 2 lymph nodes, Sox-10 was critical in distinguishing S100-positive atypical nodal dendritic cells from tumor cells. Also, Sox-10 significantly improved the identification of micrometastases and isolated tumor cells as compared with S100 in 10 positive lymph nodes. Most importantly, Sox-10 identified micrometastases in 2 lymph nodes, originally reported as negative on S100, Melan-A, and HMB-45 immunostains. Therefore, Sox-10 is a comparable marker to S100 in identifying nodal metastases in melanoma and is especially useful in the setting of lymph nodes with heavily pigmented metastases, numerous S100-positive nodal dendritic cells, micrometastases, and isolated tumor cells.

    View details for DOI 10.1097/DAD.0b013e3182042893

    View details for Web of Science ID 000291925800007

    View details for PubMedID 21552103

  • ALK-negative systemic intravascular anaplastic large cell lymphoma presenting in the skin JOURNAL OF CUTANEOUS PATHOLOGY Rieger, K. E., POLIDORE, T., Warnke, R., Kim, J. 2011; 38 (2): 216-220

    Abstract

    Systemic cases of the CD30-positive T-cell neoplasm, anaplastic large cell lymphoma (ALCL), are typically anaplastic lymphoma kinase (ALK)-positive. The failure to express ALK protein has been shown to portend a worse prognosis. We describe a case of ALK-negative systemic ALCL that presented as a violaceous plaque on the scalp of a 79-year-old man. Interestingly, the neoplastic cells were confined largely within vascular spaces, a configuration that is exceedingly rare in the skin and is more typically seen with intravascular large B-cell lymphoma. In addition, bcl-2 immunohistochemical staining was strongly positive in this case, which may portend a more aggressive clinical course. To our knowledge, this report represents the first case of an ALK-negative ALCL to present intravascularly in the skin. Therefore, the recognition of systemic anaplastic T-cell lymphoma present within the intravascular spaces is important to avoid misdiagnosis.

    View details for DOI 10.1111/j.1600-0560.2010.01528.x

    View details for Web of Science ID 000285754200009

    View details for PubMedID 20236372

  • The Use of Immunohistochemistry in the Diagnosis of Metastatic Clear Cell Renal Cell Carcinoma A Review of PAX-8, PAX-2, hKIM-1, RCCma, and CD10 ADVANCES IN ANATOMIC PATHOLOGY Sangoi, A. R., Karamchandani, J., Kim, J., Pai, R. K., McKenney, J. K. 2010; 17 (6): 377-393

    Abstract

    The diagnosis of metastatic clear cell renal cell carcinoma may be difficult in some cases, particularly in the small image-guided biopsies that are becoming more common. As targeted therapies for renal cell carcinoma are now standard treatment, the recognition and diagnosis of renal cell carcinoma has become even more critical. Many adjunctive immunohistochemical markers of renal epithelial lineage such as CD10 and RCCma have been proposed as aids in the diagnosis of metastatic renal cell carcinoma, but low specificities often limit their utility. More recently described markers (PAX-2, PAX-8, human kidney injury molecule-1, hepatocyte nuclear factor-1-?, and carbonic anhydrase-IX) offer the potential for greater sensitivity and specificity in this diagnostic setting; however, knowledge of their expected staining in other neoplasms and tissues is critical for appropriate use. In this review, we discuss the most widely used immunohistochemical markers of renal lineage with an emphasis on their sensitivity and specificity for metastatic clear cell renal cell carcinoma. Subsequently, we present a variety of organ-specific differential diagnostic scenarios in which metastatic clear cell renal cell carcinoma might be considered and we propose immunopanels for use in each situation.

    View details for DOI 10.1097/PAP.0b013e3181f89400

    View details for Web of Science ID 000283328100001

    View details for PubMedID 20966644

  • SOX10 immunostaining distinguishes desmoplastic melanoma from excision scar JOURNAL OF CUTANEOUS PATHOLOGY Ramos-Herberth, F. I., Karamchandani, J., Kim, J., Dadras, S. S. 2010; 37 (9): 944-952

    Abstract

    Sry-related HMG-BOX gene 10 (SOX10), a nuclear transcription factor that plays an important role in schwannian and melanocytic cell differentiation, has recently been shown to be a useful marker in the diagnosis of melanocytic and schwannian tumors. Fibroblasts and histiocytes that could histopathologically mimic melanoma cells often express S100, which complicates the evaluation of melanoma excision specimens for residual tumor. Distinguishing melanoma cells from immature fibrocytes or histiocytes is made more challenging in desmoplastic melanoma excision specimens.We compared the utility of melanoma markers [SOX10, S100, HMB-45, Melan-A and micropthalmia transcription factor (MiTF)] in 3 invasive, 9 desmoplastic and 14 intraepidermal melanomas. We also evaluated 18 excision scars. The staining intensity for all the cellular components in melanoma and scar specimens was scored.SOX10 strongly highlighted all in situ, invasive and desmoplastic melanomas. In contrast, MiTF expression was weak to absent in desmoplastic melanomas. In scars, S100 highlighted background spindled fibrocytes and histiocytes with greater intensity than SOX10. MiTF highlighted multi-nucleated histiocytes, while SOX10 did not.Our results showed that SOX10 was strongly expressed by desmoplastic melanoma. Furthermore, SOX10 was less likely than S100 and MiTF to be expressed by background fibrocytes and histiocytes within scars.

    View details for DOI 10.1111/j.1600-0560.2010.01568.x

    View details for Web of Science ID 000279724000007

    View details for PubMedID 20653825

  • PAX8 discriminates ovarian metastases from adnexal tumors and other cutaneous metastases JOURNAL OF CUTANEOUS PATHOLOGY Fujiwara, M., Taube, J., Sharma, M., McCalmont, T. H., Kim, J. 2010; 37 (9): 938-943

    Abstract

    The distinction of metastatic ovarian carcinoma from other metastatic carcinomas and primary adnexal lesions in the skin is often difficult. PAX8 is a transcription factor that plays a critical role in development of the Müllerian system and has been shown to be a useful discriminatory marker between ovarian and breast carcinomas. Identification of ovarian cutaneous metastases may be of benefit in patients with familial breast-ovarian carcinoma syndrome.PAX8 immunohistochemical analysis was performed on 24 cases of metastatic adenocarcinomas to the skin and compared with 7 cases of primary adnexal lesions and also compared with p63 immunohistochemical staining results. Patients with metastatic adenocarcinomas had clinically documented primary malignancies, and patients with primary adnexal carcinomas had no known history of another adenocarcinoma.Cutaneous ovarian and renal cell carcinoma metastases (2/2 and 8/8, respectively) showed positive nuclear expression of PAX8. PAX8 immunohistochemical staining in primary adnexal and other cutaneous metastases was completely negative (0/7 and 0/16, respectively). The p63 expression profile supported the distinction between adnexal and metastatic adenocarcinomas.Although cutaneous ovarian metastasis is a rare phenomenon, the prognosis is extremely poor. PAX8 expression is a useful marker that effectively discriminated metastatic ovarian carcinomas from metastatic breast carcinomas and primary adnexal tumors.

    View details for DOI 10.1111/j.1600-0560.2010.01564.x

    View details for Web of Science ID 000279724000006

    View details for PubMedID 20492080

  • A Young Girl with Weather-Beaten, Waxy Knuckles JOURNAL OF PEDIATRICS Botto, N. C., Shpall, R. L., Kim, J., Bruckner, A. L. 2010; 156 (4): 671-674

    View details for DOI 10.1016/j.jpeds.2010.01.026

    View details for Web of Science ID 000275805000029

    View details for PubMedID 20303443

  • A toddler with facial nodules: a case of idiopathic facial aseptic granuloma. Dermatology online journal Martinez-Diaz, G. J., Kim, J., Bruckner, A. L. 2010; 16 (1): 9-?

    Abstract

    We describe the case of a 3-year-old boy who presented with several asymptomatic facial nodules present for six months. A skin biopsy obtained from the nodules showed a moderately well-defined granuloma in the superficial and deep dermis. A squamous epithelial lined cyst, extravasated keratin, or shadow cells were not identified. Bartonella henselae titers and the Coccidioidomycosis immitis immunodiffusion test were negative; a Tuberculin Skin Test was non-reactive. Fite, Periodic acid-Schiff (PAS) and Gomori-Grocott methenamine silver (GMS) stains failed to identify microorganisms. In addition, tissue cultures for bacteria, fungus, and acid fast bacilli were negative. In light of the clinical findings, histology, and negative cultures, a diagnosis of idiopathic facial aseptic granuloma (IFAG) was made. After the biopsy, the child was treated with erythromycin and clarithromycin, each for one month, and the lesions slowly improved.

    View details for PubMedID 20137751

  • A Rectangular Dermatosis of the Left Back ARCHIVES OF DERMATOLOGY Craiglow, B., Kim, J., Watsky, K., Heald, P. 2009; 145 (12): 1411-1414

    Abstract

    Cardioversion and defibrillation have become widely used techniques aimed at restoring normal sinus rhythm in patients with cardiac arrhythmias. Following the procedure, cutaneous lesions are often seen at the site of the electrodes, but little has been reported regarding the evolution of such lesions over time.Two patients presented with unusual, well-defined rectangular eruptions on the left back, and both reported a history of having undergone electrical cardioversion or defibrillation several years previously. The histologic characteristics of each lesion were distinct, and the management was symptomatic, with most of the relief coming from the recognition that the eruption was actually a self-limited manifestation of cardioversion and defibrillation.The clinical cases and corresponding histologic findings represent possible long-term sequelae of electrical cardioversion or defibrillation. They are presented in order to enhance the diagnostic acumen of dermatologists and to avoid potential misdiagnosis.

    View details for Web of Science ID 000272693400010

    View details for PubMedID 20026851

  • Linear Pruritic Eruption With Onychodystrophy in a 1-Year-Old Girl Lichen striatus ARCHIVES OF DERMATOLOGY Ramos-Herberth, F., Bishop, K., Kim, J. 2009; 145 (9): 1053-1058

    View details for Web of Science ID 000270041300019

    View details for PubMedID 19770450

  • Annular and Keratotic Papules and Plaques in a Teenager ARCHIVES OF DERMATOLOGY Diaz, G. J., Berk, D., Bruckner, A. L., Kim, J. 2009; 145 (8): 931-U61

    View details for Web of Science ID 000269020600017

    View details for PubMedID 19687428

  • Keloidal atypical fibroxanthoma: a case series JOURNAL OF CUTANEOUS PATHOLOGY Kim, J., McNiff, J. M. 2009; 36 (5): 535-539

    Abstract

    Keloidal atypical fibroxanthoma (AFX) is a rare variant of AFX with thick bands of hyalinized collagen. The identification of keloidal collagen associated with fibrohistiocytic cells may erroneously lead to the diagnosis of keloidal dermatofibroma. Although AFX is a pleomorphic cutaneous tumor typically associated with a good prognosis, occasional reports of metastatic AFX highlight the importance of accurate identification.A total of nine cases of an unusual variant of AFX with keloidal tumoral sclerosis were collected and examined. The cases were stained with antibodies directed against S100, cytokeratin, CD68 and CD31.Histopathological examination revealed pleomorphic cells trapped within hyalinized keloidal collagen bands. In several cases, the keloidal collagen also formed ring-shaped structures surrounding CD31-positive vascular structures. Pleomorphic cells were negative for S100 protein and keratin, but consistently labeled with antibodies directed against CD68.The diagnosis of keloidal AFX requires the exclusion of other malignant and benign lesions with keloidal or sclerotic collagen. Awareness of the rare variant of keloidal AFX may avoid a diagnostic pitfall leading to an erroneous diagnosis, particularly in small biopsies. The finding of sclerotic collagen preferentially deposited around vessels is an interesting and poorly understood phenomenon.

    View details for DOI 10.1111/j.1600-0560.2008.01084.x

    View details for Web of Science ID 000264731100006

    View details for PubMedID 19476521

  • Eyebrow papule in an elderly man. Dermatology online journal Clark, F. L., Somoano, B., Taube, J., Egbert, B., Kim, J. 2009; 15 (9): 14-?

    Abstract

    A 70-year-old Caucasian man presented with a several-month history of a solitary, asymptomatic papule on the left eyebrow. His medical history included stage 1A lentigo maligna melanoma and multiple non-melanoma skin cancers. Physical examination demonstrated a solitary 5-mm smooth, dome-shaped skin colored papule with subtle central erosion on the left eyebrow. No overlying telangiectasias were noted. A biopsy of the lesion was performed. The lesion was composed of plump spindle cells arranged in a plexiform pattern in the background of thick, keloidal collagen bundles. The lesional cells were NKI/C3-positive and S-100-negative. A diagnosis of cellular neurothekeoma was made.

    View details for PubMedID 19931001

  • Pemphigoid vegetans: a case report and review of the literature JOURNAL OF CUTANEOUS PATHOLOGY Kim, J., Chavel, S., Girardi, M., McNiff, J. M. 2008; 35 (12): 1144-1147

    Abstract

    Pemphigoid vegetans is an exceptionally rare intertriginous variant of bullous pemphigoid characterized by vegetative and purulent lesions present in the groin, axillae, thighs, hands, eyelids and perioral regions. The clinical, histopathological and immunofluorescent profile of a new case of pemphigoid vegetans in a 79-year-old man is reported. Our patient had papillomatous plaques with pustules in the bilateral inguinal folds, which clinically resembled pemphigus vegetans. Also suggesting pemphigus vegetans, an initial skin biopsy showed eosinophilic spongiosis, while a second biopsy showed histological and immunological features diagnostic of pemphigoid. Because only a few cases of pemphigoid vegetans have been reported in the literature, clinical and morphological data are scant. Most reported cases were successfully treated with topical antibiotics or steroids; therefore, appropriate diagnosis of this rare lesion will assist management.

    View details for DOI 10.1111/j.1600-0560.2008.01016.x

    View details for Web of Science ID 000260536400011

    View details for PubMedID 18988318

  • Nuclear expression of survivin portends a poor prognosis in Merkel cell carcinoma MODERN PATHOLOGY Kim, J., McNiff, J. M. 2008; 21 (6): 764-769

    Abstract

    Inhibition of apoptosis is a critical step in tumorigenesis in many cancers, including Merkel cell carcinoma; however, the exact regulatory mechanisms are not fully understood. Survivin is an inhibitor of apoptosis that is undetectable in most terminally differentiated normal human tissues, strongly expressed in embryonic and fetal organs and is strongly expressed in many different human cancers. In this study, we investigated the expression of survivin in cutaneous Merkel cell carcinoma using immunohistochemistry and correlated the findings with long-term clinical follow-up. We collected and immunostained 19 cases of Merkel cell carcinoma with antibodies to survivin. The median patient age was 79 years, with an average follow-up of 17 months, and a male/female ratio of 7:11. All but one sample represented primary lesions and two cases were obtained from one patient. Clinical follow-up was obtained in 15 cases (79%). All 19 cases of Merkel cell carcinoma demonstrated strong immunoreactivity for survivin. Survivin protein was localized and classified into predominately nuclear (N=8) or cytoplasmic (N=4) compartments. A mixed pattern of survivin expression was also seen in three cases. Cases with a nuclear staining pattern were distinguished by an aggressive clinical course, with seven of eight patients developing metastases or dead of disease on follow-up. Furthermore, all of the cases with predominately cytoplasmic survivin localization (N=4) were free of disease on follow-up. Merkel cell carcinomas represent aggressive malignancies regulated by apoptotic pathways. We demonstrate that survivin, a protein with a dual role in inhibition of apoptosis and regulation of cellular proliferation is expressed in Merkel cell carcinoma. Moreover, nuclear subcellular localization of survivin in Merkel cell carcinomas may portend a poor prognosis and identification of these cases may assist clinical management.

    View details for DOI 10.1038/modpathol.2008.61

    View details for Web of Science ID 000256112900016

    View details for PubMedID 18425079

  • Congenital panfollicular nevus associated with polydactyly JOURNAL OF CUTANEOUS PATHOLOGY Kim, J., Zambrano, E. V., McNiff, J. M. 2007; 34: 14-17

    Abstract

    A 2-year-old girl presented with ulnar-sided duplication of the left thumb distal to the interphalangeal joint and syndactyly of the first web space. She also had several asymptomatic pink-tan cutaneous papules, involving the first and second ray of the left hand and wrist, clinically resembling a linear epidermal nevus. Microscopically, the papules were composed of well-circumscribed aggregates of basaloid epithelium within the dermis. No normal hair follicles were identified. Follicular germ and papillae were identified, representing abortive attempts at hair follicle formation. The features were remarkably similar to a novel entity described by Finn and Argenyi as congenital panfollicular nevus. In our case, the congenital panfollicular nevus was associated with distal thumb polysyndactyly, which may suggest an important link between limb patterning and hair follicle development.

    View details for DOI 10.1111/j.1600-0560.2006.00714.x

    View details for Web of Science ID 000250842500003

    View details for PubMedID 17997731

  • Autoimmune pancreatitis presenting as simultaneous masses in the pancreatic head and gallbladder. JOP : Journal of the pancreas Gumbs, A. A., Kim, J., Kiehna, E., Brink, J. A., Salem, R. R. 2005; 6 (5): 455-459

    Abstract

    Autoimmune pancreatitis is a rare variant of chronic pancreatitis characterized by pancreatic ductal narrowing and pancreatic parenchymal edema on computed tomography and rarely with intermittent attacks of abdominal pain. Recently, it has been found to be a systemic disease with lymphoplasmacytic infiltration that has been associated with several autoimmune diseases and described in multiple organs including the extrahepatic bile duct, liver and gallbladder.We describe the clinical, radiographic and histopathologic aspects of a patient who presented with synchronous masses in the pancreatic head and gallbladder. Postoperatively, the patient's jaundice subsided and IgG4 levels, which were drawn one week postoperatively, were all within normal limits. Nonetheless, immunohistochemical staining for IgG4 was positive.Autoimmune pancreatitis is the most common benign entity identified in patients that underwent pancreaticoduodenectomy for presumed pancreatic adenocarcinoma. Our patient with autoimmune pancreatitis presented with simultaneous inflammatory masses in the gallbladder and pancreatic head, an association not previously reported. Preoperative evaluation of IgG4 or autoantibody levels may have obviated the need for an operation. Therefore, we have begun screening for elevated serum IgG4 concentrations to identify patients with possible autoimmune pancreatitis who present without definitive pathological or radiographic evidence for malignancy. If pre-operative diagnosis is not made, immunohistochemical staining of pathology specimens can confirm the diagnosis.

    View details for PubMedID 16186668

  • Recruitment of CXCR3(+) and CCR5(+) T cells and production of interferon-gamma-inducible chemokines in rejecting human arteries AMERICAN JOURNAL OF TRANSPLANTATION Burns, W. R., Wang, Y. N., Tang, P. C., Ranjbaran, H., Iakimov, A., Kim, J., Cuffy, M., Bai, Y., Pober, J. S., Tellides, G. 2005; 5 (6): 1226-1236

    Abstract

    Chemokine receptors preferentially expressed by Th1 cells and their IFN-gamma-inducible ligands predominate in experimental and clinical allograft rejection. Previous chemokine-related transplantation studies have focused on parenchymal and microvascular inflammation which are of importance in acute rejection, but are not necessarily relevant in immune-mediated injury of conduit arteries. We have recently described a model of progressive human T cell-mediated infiltration and injury of allogeneic coronary artery segments using immunodeficient mouse hosts. In the present study, we investigated if recruitment of allogeneic T cells to different vascular compartments correlated with the expression of chemokines and their receptors. Transcripts were quantified by laser capture microdissection/real-time RT-PCR and their distribution was correlated to the corresponding protein expression detected by immunohistochemistry. Infiltrating T cells, confined to the adventitia and intima, expressed CXCR3 and CCR5, but were not recruited into the media despite production by vascular smooth muscle cells of IP-10, Mig, I-TAC, RANTES and MIP-1beta. Chemokine mRNA was detected primarily in vascular cells, although chemokine protein largely localized to infiltrating leukocytes which uniquely expressed their cognate receptors. These data explain the recruitment of IFN-gamma-secreting T cells to the vessel wall, and reinforce the suggestion that the arterial media may be a site of immunological privilege.

    View details for DOI 10.1111/j.1600-6143.2005.00892.x

    View details for Web of Science ID 000229031400008

    View details for PubMedID 15888026

  • Localization and signaling of gp subunit ste4p are controlled by a-factor receptor and the a-specific protein asg7p MOLECULAR AND CELLULAR BIOLOGY Kim, J. A., Bortz, E., Zhong, H. L., Leeuw, T., Leberer, E., Vershon, A. K., Hirsch, J. P. 2000; 20 (23): 8826-8835

    Abstract

    Haploid yeast cells initiate pheromone signaling upon the binding of pheromone to its receptor and activation of the coupled G protein. A regulatory process termed receptor inhibition blocks pheromone signaling when the a-factor receptor is inappropriately expressed in MATa cells. Receptor inhibition blocks signaling by inhibiting the activity of the G protein beta subunit, Ste4p. To investigate how Ste4p activity is inhibited, its subcellular location was examined. In wild-type cells, alpha-factor treatment resulted in localization of Ste4p to the plasma membrane of mating projections. In cells expressing the a-factor receptor, alpha-factor treatment resulted in localization of Ste4p away from the plasma membrane to an internal compartment. An altered version of Ste4p that is largely insensitive to receptor inhibition retained its association with the membrane in cells expressing the a-factor receptor. The inhibitory function of the a-factor receptor required ASG7, an a-specific gene of previously unknown function. ASG7 RNA was induced by pheromone, consistent with increased inhibition as the pheromone response progresses. The a-factor receptor inhibited signaling in its liganded state, demonstrating that the receptor can block the signal that it initiates. ASG7 was required for the altered localization of Ste4p that occurs during receptor inhibition, and the subcellular location of Asg7p was consistent with its having a direct effect on Ste4p localization. These results demonstrate that Asg7p mediates a regulatory process that blocks signaling from a G protein beta subunit and causes its relocalization within the cell.

    View details for Web of Science ID 000168366000019

    View details for PubMedID 11073983

  • Receptor inhibition of pheromone signaling is mediated by the Ste4p G(beta) subunit MOLECULAR AND CELLULAR BIOLOGY Kim, J., Couve, A., Hirsch, J. P. 1999; 19 (1): 441-449

    Abstract

    The pheromone response pathway of the yeast Saccharomyces cerevisiae is initiated in MATa cells by binding of alpha-factor to the alpha-factor receptor. MATa cells in which the a-factor receptor is inappropriately expressed exhibit reduced pheromone signaling, a phenomenon termed receptor inhibition. In cells undergoing receptor inhibition, activation of the signaling pathway occurs normally at early time points but decreases after prolonged exposure to pheromone. Mutations that suppress the effects of receptor inhibition were obtained in the STE4 gene, which encodes the beta-subunit of the G protein that transmits the pheromone response signal. These mutations mapped to the N terminus and second WD repeat of Ste4p in regions that are not part of its Galpha binding surface. A STE4 allele containing several of these mutations, called STE4(SD13), reversed the signaling defect seen at late times in cells undergoing receptor inhibition but had no effect on the basal activity of the pathway. Moreover, the signaling properties of STE4(SD13) were indistinguishable from those of STE4 in wild-type MATa and MATalpha cells. These results demonstrate that the effect of the STE4(SD13) allele is specific to the receptor inhibition function of STE4. STE4(SD13) suppressed the signaling defect conferred by receptor inhibition in a MATa strain containing a deletion of GPA1, the G protein alpha-subunit gene; however, STE4(SD13) had no effect in a MATalpha strain containing a GPA1 deletion. Suppression of receptor inhibition by STE4(SD13) in a MATa strain containing a GPA1 deletion was unaffected by deletion of STE2, the alpha-factor receptor gene. The results presented here are consistent with a model in which an a-specific gene product other than Ste2p detects the presence of the a-factor receptor and blocks signaling by inhibiting the function of Ste4p.

    View details for Web of Science ID 000077647100043

    View details for PubMedID 9858568

  • A nucleolar protein that affects mating efficiency in Saccharomyces cerevisiae by altering the morphological response to pheromone GENETICS Kim, J., Hirsch, J. P. 1998; 149 (2): 795-805

    Abstract

    SSF1 and SSF2 are redundant essential yeast genes that, when overexpressed, increase the mating efficiency of cells containing a defective Ste4p Gbeta subunit. To identify the precise function of these genes in mating, different responses to pheromone were assayed in cells that either lacked or overexpressed SSF gene products. Cells containing null alleles of both SSF1 and SSF2 displayed the normal transcriptional induction response to pheromone but were unable to form mating projections. Overexpression of SSF1 conferred the ability to form mating projections on cells containing a temperature-sensitive STE4 allele, but had only a small effect on transcriptional induction. SSF1 overexpression preferentially increased the mating efficiency of a strain containing a null allele of SPA2, a gene that functions specifically in cell morphology. To investigate whether Ssf1p plays a direct physical role in mating projection formation, its subcellular location was determined. An Ssf1p-GFP fusion was found to localize to the nucleolus, implying that the role of SSF gene products in projection formation is indirect. The region of Ssf1p-GFP localization in cells undergoing projection formation was larger and more diffuse, and was often present in a specific orientation with respect to the projection. Although the function of Ssf1p appears to originate in the nucleus, it is likely that it ultimately acts on one or more of the proteins that is directly involved in the morphological response to pheromone. Because many of the proteins required for projection formation during mating are also required for bud formation during vegetative growth, regulation of the activity or amount of one or more of these proteins by Ssf1p could explain its role in both mating and dividing cells.

    View details for Web of Science ID 000074028400028

    View details for PubMedID 9611192

Stanford Medicine Resources: