Publications by authors named "Walter M Klein"

10 Publications

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Metastatic Melanoma With Features of Desmoplastic Melanoma in a Patient With Primary Cutaneous Superficial Spreading Melanoma With Epithelioid Features.

Am J Dermatopathol 2021 Jan 12. Epub 2021 Jan 12.

Department of Pathology and Laboratory Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA; Division of Dermatology and Department of Pathology, University of Washington, Seattle, WA; Department of Pathology, Bryn Mawr Hospital, Bryn Mawr, PA; and Department of Surgery, Hospital of University of Pennsylvania, Philadelphia, PA.

Abstract: The synchronous incidence of 2 different subtypes of melanoma is very rare. Desmoplastic melanoma (DM) can be a diagnostic challenge because of its frequent appearance as a dermal banal spindle cell proliferation. We present a case of a 30-year-old man who developed an irregular, purple, tender plaque measuring 2.5 cm on the right pretibial region. Wide excision of the right leg lesion showed superficial spreading melanoma with epithelioid cells and no spindle cell component. Sentinel lymph node (SLN) biopsy showed an atypical melanocytic proliferation involving one inguinal lymph node with subcapsular and intraparenchymal components. There were spindled tumor cells in lymph node capsule with hyperchromatic nuclei, which were nested within desmoplastic stroma, and were S100- and SOX10-positive and MART1- and HMB-45 negative; in addition to epithelioid tumor cells, which were S100-, SOX10-, and MART1-positive. Multiple discontinuous foci, subcapsular atypical melanocytes, and extracapsular extension helped in excluding capsular nevus. These findings were consistent with DM. Herein, we present an unusual case of primary cutaneous superficial spreading melanoma of the right leg with a predominantly epithelioid morphology that developed metastases to the SLN. The metastasis exhibited divergent differentiation, including both epithelioid morphology identical to the primary, but with additional features of DM that were nonoverlapping with the primary lesion.
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http://dx.doi.org/10.1097/DAD.0000000000001898DOI Listing
January 2021

#dermpathJC: The first online dermatopathology Twitter journal club.

J Cutan Pathol 2018 05 26;45(5):370-373. Epub 2018 Feb 26.

University of Arkansas for Medical Sciences, Little Rock, Arkansas.

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http://dx.doi.org/10.1111/cup.13110DOI Listing
May 2018

Follicular induction overlying a dermatofibrosarcoma protuberans.

Am J Dermatopathol 2014 Feb;36(2):186-8

*Department of Dermatology, Ilsan Paik Hospital, Inje University School of Medicine, Goyang, South Korea; †Department of Dermatology, University of Pennsylvania, Philadelphia, PA; and ‡Department of Pathology, Main Line Pathology Associates, Bryn Mawr Hospital, Bryn Mawr, PA.

The term "induction" has been used to describe epidermal changes overlying a dermatofibroma (DF). Follicular induction is most often associated with DF, but can be observed in other lesions, including focal mucinosis, nevus sebaceous, seborrheic keratosis, wart, neurofibroma, and scars. Dermatofibrosarcoma protuberans (DFSP) is a malignant fibrohistiocytic tumor that may be difficult to distinguish from DF. In contrast to DF, the epidermis overlying DFSP is usually attenuated or ulcerated. Here, we report a case of DFSP exhibiting follicular induction of the overlying epidermis. This epidermal change has been rarely reported in DFSP and may present a diagnostic pitfall in superficially sampled lesions.
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http://dx.doi.org/10.1097/DAD.0b013e3182a64a02DOI Listing
February 2014

Increased expression of stem cell markers in malignant melanoma.

Mod Pathol 2007 Jan 24;20(1):102-7. Epub 2006 Nov 24.

Department of Pathology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215, USA.

The potential role of stem cells in neoplasia is a subject of recent interest. Three markers of melanocytic stem cells have been described recently. CD166 is expressed on the surface of mesenchymal stem cells and has been found on human melanoma cell lines. CD133 is expressed on the surface of dermal-derived stem cells that are capable of differentiating into neural cells. Nestin is an intermediate filament expressed in the cytoplasm of neuroepithelial stem cells. In this study, we evaluate the expression of these markers and possible differences among banal nevi, primary melanoma, and metastastic melanoma. Tissue microarrays containing normal tissue and 226 melanocytic lesions (71 banal nevi, 71 in situ and invasive melanomas, and 84 metastatic melanomas) were studied by immunohistochemistry using monoclonal antibodies CD166, CD133, and nestin. A significantly greater percentage of melanomas (combined primary and metastatic) contained cells that expressed CD166 (P=0.005), CD133 (P=0.003), and nestin (P=0.03) than banal nevi. Only nestin showed a statistical difference when comparing primary and metastatic melanoma (P=0.05). A stepwise increase in the proportion of lesions expressing all three markers was observed from banal nevi (2/19) to primary melanomas (8/17) to metastatic melanoma (19/28), P=0.0005. All cases of metastatic melanoma expressed at least one stem cell marker. The increased expression of CD166, CD133, and nestin in melanoma suggests that progression to malignant melanoma likely involves genetic pathways instrumental to stem cell biology and normal tissue development. Further studies and characterization of these pathways may also reveal new prognostic markers for a disease whose prognosis in advanced stages is dismal.
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http://dx.doi.org/10.1038/modpathol.3800720DOI Listing
January 2007

Primary liver carcinoma arising in people younger than 30 years.

Am J Clin Pathol 2005 Oct;124(4):512-8

Department of Pathology, the Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.

Primary liver carcinomas in children and young adults are uncommon and poorly described. We examined primary liver carcinomas in people younger than 30 years and performed immunostains for markers of biliary (cytokeratin [CK] 7, CK19, CD56) and hepatocellular (HepPar) differentiation. We found 23 primary liver carcinomas were found: 13 hepatocellular carcinomas (HCCs), 9 fibrolamellar carcinomas (FLCs), and 1 cholangiocarcinoma. Most HCCs showed compact (n = 7) or trabecular (n = 4) growth patterns. The Edmondson grades were as follows: 1, 3 tumors; 2, 8 tumors; and 3, 2 tumors). All HCCs and FLCs were HepPar(+). All FLCs and 7 of 9 HCCs were CK7(+). In contrast, a control group of 65 adult HCCs showed less CK7 positivity (24 [37%]; P = .03). CK19 was positive in 2 HCCs and CD56 in 1 HCC. No chronic background liver disease was seen, although 3 cases showed foci of altered hepatocytes. HCCs are the most common primary liver carcinoma in children and young adults followed by FLCs. They are morphologically similar to adult HCC, but more likely to be CK7(+).
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http://dx.doi.org/10.1309/TT0R7KAL32228E99DOI Listing
October 2005

Peripancreatic tuberculosis mimicking pancreatic neoplasia.

J Gastrointest Surg 2005 Feb;9(2):254-62

Department of Surgery, The Johns Hopkins Medical Institutions, Baltimore, Maryland 21287-4606, USA.

Tuberculosis of the pancreas and peripancreatic lymph nodes is an extremely rare disorder that has been reported with increased frequency in the past several years. Despite the fact that abdominal tuberculosis can generally be managed by pharmacotherapy alone, invasive procedures are often used before the establishment of the correct diagnosis, sometimes leading to unnecessary interventions and delayed treatment. To set the stage for our review, we first describe a case of a 31-year-old woman from India who initially presented with nonspecific symptoms and a pancreatic cystic lesion but was later diagnosed with peripancreatic tuberculosis. We then present a review of the current literature on peripancreatic and pancreatic tuberculosis, with a focus on diagnosis and management of the disease, but we also touch on issues such as epidemiology, infection control, and tissue acquisition. Finally, we offer clues that can be used to help identify patients who present with otherwise vague symptoms who may harbor pancreatic or peripancreatic tuberculosis. It is our hope that this case report and review of the literature will raise awareness and improve the management of this uncommon but serious disorder.
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http://dx.doi.org/10.1016/j.gassur.2004.06.010DOI Listing
February 2005

Multicentric plasma cell variant of Castleman's disease with cutaneous involvement.

J Cutan Pathol 2004 Jul;31(6):448-52

Department of Pathology, The Johns Hopkins Medical Institutions, Baltimore, MD, USA.

Background: Castleman's disease (CD) is a rare low-grade B-cell lymphoproliferative disorder that can be associated with a variety of antibody-mediated paraneoplastic syndromes. The disease is classified clinically by two forms and three histologic variants.

Methods: We describe the clinical and pathological features of a 44-year-old woman who presented with an autoimmune hemolytic anemia, thrombocytosis, polyclonal gammopathy, axillary lymphadenopathy, hepatosplenomegaly, and several erythematous and violaceous nodules and plaques without scaling involving the trunk and extremities.

Results: Histologic examination of the skin lesions revealed a deep dermal and subcutaneous nodular mononuclear infiltrate composed primarily of polyclonal plasmacytoid cells without atypia and an increased vascular proliferation. Additional studies including a bone marrow and lymph node biopsy, serum and urine protein electrophoresis, and computed tomography scans supported the diagnosis of multicentric plasma cell variant of CD with an associated autoimmune paraneoplastic hemolytic anemia.

Conclusion: Cutaneous involvement in CD is part of the multicentric nature and should be considered in the differential diagnosis of a polyclonal plasma cell-rich lymphoproliferative disorder associated with paraneoplastic autoimmune disease.
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http://dx.doi.org/10.1111/j.0303-6987.2004.00117.xDOI Listing
July 2004

CD10 imunostaining does not distinguish endometrial carcinoma invading myometrium from carcinoma involving adenomyosis.

Am J Surg Pathol 2003 Jun;27(6):786-9

Department of Pathology, John Hopkins Medical Institutions, Baltimore, Maryland 21231-2410, USA.

The distinction of involvement of adenomyosis by endometrial carcinoma from endometrial carcinoma invading the myometrium can at times be difficult. This distinction, however, is important from the standpoint of staging, treatment, and prognosis because the outcome of carcinoma invading the myometrium as compared with involving adenomyosis is significantly worse. CD10 has been recently reported to be expressed by normal and neoplastic endometrial stromal cells. We therefore hypothesized that CD10 may be helpful in distinguishing carcinoma within adenomyosis from endometrial carcinoma directly invading the myometrium. Twenty-two cases of invasive endometrioid adenocarcinoma were identified from the surgical pathology files of the Johns Hopkins Hospital and consultation files of one of the authors (R.J.K.) and immunostained for CD10, desmin, and caldesmon. The pattern of staining was compared with five cases in which carcinoma was confined to adenomyosis. As a control, 14 cases of adenomyosis unassociated with carcinoma were included in the analysis. All 22 endometrial carcinomas that invaded the myometrium expressed CD10 to some extent in cells immediately surrounding the neoplastic glands. In 18, all of the invasive nests displayed CD10 in surrounding cells, but in four cases the staining was patchier, involving the surrounding cells of approximately 50-75% of the invasive nests. In four cases of myoinvasive carcinoma, the CD10-positive cells surrounding the nests of invasive carcinoma were also positive for desmin and caldesmon. In the remaining 18 cases with myoinvasive carcinoma, the cells surrounding the carcinomas failed to react with desmin and caldesmon. All five endometrial carcinomas involving adenomyosis displayed CD10 positivity in what appeared to be endometrial stromal cells surrounding the neoplastic glands. The stromal cells were negative for desmin and caldesmon. The control cases of adenomyosis were all positive for CD10, although in four cases the staining was patchy compared with 10 cases in which it was diffuse. Desmin and caldesmon were negative in all of these cases. Although CD10 identifies endometrial stromal cells in the endometrium and in adenomyosis and endometriosis, this study demonstrates that CD10 does not aid in distinguishing myometrial invasion of endometrial carcinoma from involvement of adenomyosis by endometrial carcinoma because the cells surrounding the tumor in the myoinvasive group express CD10.
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http://dx.doi.org/10.1097/00000478-200306000-00009DOI Listing
June 2003

Lack of expression of c-kit protein (CD117) in mesenchymal tumors of the uterus and ovary.

Int J Gynecol Pathol 2003 Apr;22(2):181-4

Department of Pathology,The Johns Hopkins Medical Institutions, Baltimore, Maryland, USA.

c-kit is a proto-oncogene that codes for a transmembrane tyrosine kinase receptor (CD117). The gene product KIT is constitutively overexpressed in mastocytosis and gastrointestinal stromal tumors. Recently the use of the tyrosine kinase inhibitors, such as STI-571, has resulted in the successful treatment of bcr-abl-positive leukemias and gastrointestinal stromal tumors. In gastrointestinal stromal tumors, immunostaining for c-kit is diffusely positive. Because the expression of c-kit in mesenchymal tumors of the uterus and ovary has not been previously studied, we evaluated its expression in 38 of these tumors by immunohistochemistry. The number of positive labeled/total tumors were as follows: 0/8 malignant mullerian mixed tumors, 4/7 ovarian fibrosarcomas, 0/1 clear-cell ovarian sarcoma, 0/4 uterine leiomyosarcomas, 1/10 low-grade endometrial stromal sarcomas, 0/2 high-grade endometrial stromal sarcomas, and 3/6 endometrial stromal nodules. In all positive cases, no more than 5% of the cells were labeled. In conclusion, unlike gastrointestinal stromal tumors, mesenchymal tumors of the uterus and ovary rarely express c-kit. Therefore, it is unlikely that patients with these tumors will benefit from treatment with the currently available tyrosine kinase inhibitors.
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http://dx.doi.org/10.1097/00004347-200304000-00011DOI Listing
April 2003

Direct correlation between proliferative activity and dysplasia in pancreatic intraepithelial neoplasia (PanIN): additional evidence for a recently proposed model of progression.

Mod Pathol 2002 Apr;15(4):441-7

Department of Pathology, The Johns Hopkins Medical Institutions, Baltimore, Maryland 21205, USA.

A growing body of morphological, clinical, and genetic observations suggests a progression model for pancreatic ductal adenocarcinoma. In this model, pancreatic ducts progress through a series of architectural and cytological changes that define degrees of pancreatic intraepithelial neoplasia (PanIN). Expressed in dividing cells, Ki-67 has been extensively used as a proliferation marker. Its expression in different grades of PanIN has not been well studied. A total of 76 PanINs from 41 patients were histologically graded according to recently established criteria. These PanINs were then immunolabeled with a monoclonal antibody against Ki-67 (Mib-1). Normal ducts and invasive ductal adenocarcinomas were also labeled with the antibody. In 15 normal ducts, only 0.41% of the epithelial cells expressed Ki-67. Ki-67-labeling indices in the increasing grades of PanIN were as follows: PanIN-1A, 0.69%; PanIN-1B, 2.33%; PanIN-2, 14.08%; and PanIN-3, 22.01%. Fifteen invasive ductal adenonocarcinomas showed an average labeling index of 36.99%. The difference in Ki-67 labeling among these groups was statistically significant (P <.0005, Kruskal-Wallis test). This pattern of proliferation provides additional evidence supporting the recently proposed pancreatic progression model. It also correlates well with known molecular changes, such as activating point mutations in the K-ras oncogene and the loss of DPC4 and p16 gene expression. Ki-67 staining may be useful as an adjunct in the diagnosis of precancerous lesions in the pancreas and may provide a reliable way to identify lesions at high risk for the subsequent development of infiltrating carcinoma.
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http://dx.doi.org/10.1038/modpathol.3880544DOI Listing
April 2002