Debra L. Zynger

Glypican 3: A novel marker in testicular germ cell tumors

Glypican 3 (GPC3), a membrane-bound heparin sulfate proteoglycan, may play a role in promoting embryonic cell growth and differentiation. GPC3 is mutated in Simpson-Golabi-Behmel syndrome, characterized by tissue overgrowth and an increased risk of embryonal malignancies. Recently, GPC3 was reported to be one of the over-expressed genes in testicular yolk sac tumors by gene expression microarray analysis. However, the presence of the GPC3 protein in germ cell tumors has never been investigated. The purpose of the study was to investigate the GPC3 expression in various histologic components of testicular germ cell tumors using immunohistochemistry and to assess its possible utility as a diagnostic marker. Tumors from 71 patients were examined, including components of 42 seminomas, 37 embryonal carcinomas, 24 yolk sac tumors, 20 teratomas with mature elements, 16 teratomas with immature elements, and 7 choriocarcinomas. Cytoplasmic and membranous immunoreactivity was semiquantitatively evaluated. All yolk sac tumor (24/24) and choriocarcinoma (7/7) components were immunoreactive for GPC3, whereas only 38% of teratomas with immature elements and 8% of embryonal carcinomas expressed GPC3. There was no immunoreactivity in benign testicular tissue, intratubular germ cell neoplasia, seminomas (0/42), or teratomas with mature elements (0/20). We conclude that the oncofetal protein GPC3 is a novel immunohistochemical marker in testicular germ cell tumors with differential expression in defined histologic subtypes. Our findings suggest a possible role of GPC3 in tumor cell differentiation. Furthermore, GPC immunostaining may be useful in the pathologic diagnosis of nonseminomatous germ cell tumors, particularly yolk sac tumor, and choriocarcinoma.

Expression of glypican 3 in ovarian and extragonadal germ cell tumors.

Germ cell tumors (GCTs), rare malignancies that occur in a wide range of locations and display variable histologic patterns, may pose diagnostic challenges. Glypican 3 (GPC3), a membrane-bound heparan sulfate proteoglycan, has been shown to be a novel diagnostic marker in testicular GCT. However, GPC3 expression in ovarian and extragonadal GCT has not been reported. We evaluated GPC3 immunoreactivity in GCTs from 63 patients (57 children and 6 adults), including 14 ovarian and 20 extragonadal primary GCTs and 8 metastases along with 21 primary testicular GCTs for comparison. All 33 yolk sac tumors (YSTs) and both choriocarcinomas were immunoreactive for GPC3. In contrast, a minority of immature (4/10) and mature (4/35) teratomas were positive. No positivity was seen in 6 embryonal carcinomas or 5 germinomas. GPC3 is differentially expressed in ovarian and extragonadal GCTs, with expression predominantly observed in YSTs and choriocarcinoma.

Glomus Tumor of the Kidney: Case Report and Literature Review

Glomus tumor is a benign mesenchymal neoplasm of the subcutaneous tissue of the distal extremities and head and neck region. Glomus tumor rarely occurs in the visceral organs. This study reports the sixth case of a glomus tumor arising in the kidney in a 62-year-old man who presented with weight loss and an incidental kidney lesion detected by computed tomographic scan. Radiologically, the tumor was difficult to differentiate from a malignant lesion and was therefore excised by partial nephrectomy. The tumor was challenging to diagnose by routine hematoxylin and eosin microscopic examination, necessitating immunohistochemical analysis. Immunoreactivity was demonstrated for smooth muscle actin, vimentin, collagen IV, and CD57, with little to no expression of neuroendocrine, endothelial, or epithelial markers. To date, the tumor has followed a benign course without evidence of local recurrence or metastasis.

Blue rubber bleb nevus syndrome: novel lymphangiomatosis-like growth pattern within the uterus and immunohistochemical analysis.

Blue Rubber Bleb Nevus Syndrome is a rare, primarily sporadic condition characterized by vascular lesions principally involving the skin and gastrointestinal tract. Although considered a venous malformation, telangiectatic capillaries, arteriovenous malformations, and lymphangiomas have been reported, but a lymphangiomatosis-like growth pattern has not been described. This case of Blue Rubber Bleb Nevus Syndrome demonstrated a labyrinth of variably sized vascular spaces lined by an attenuated layer of bland endothelial cells, dissecting uterine tissues and sequestering remaining myometrium. Immunohistochemical profile of lesional endothelial cells from the myometrium included strong, diffuse CD31; variable CD34; strong, patchy D2-40; weak, patchy factor VIII-related antigen; focal linear subendothelial collagen type IV; Ki-67 in 1% of cells; and no GLUT-1 or WT1 expression. This report expands the morphological spectrum of vascular lesions in Blue Rubber Bleb Nevus Syndrome to include a lymphangiomatosis-like growth pattern and the immunohistochemistry suggests dual vascular and lymphatic differentiation, supporting the current belief that these lesions are malformations.

Differential expression of neural-cadherin in pulmonary epithelial tumours

Aims:  Neural (N)‐cadherin belongs to a group of transmembrane molecules with a crucial role in tissue morphogenesis and maintenance of an epithelioid phenotype and increased N‐cadherin expression is implicated in tumour progression and dedifferentiation. The aim was to determine whether evaluation of N‐cadherin in pulmonary tumours might assist in identifying lesions with more aggressive potential.

Immunohistochemical Profile of Paratesticular Serous Papillary Adenocarcinoma and Tunica Vaginalis Facilitates Distinction From Malignant Mesothelioma

Testicular and paratesticular tumors resembling mullerian epithelium of the ovary are extremely uncommon. This study reports a case of paratesticular serous papillary adenocarcinoma (SPA) in an 87-year-old man that was misdiagnosed as malignant mesothelioma (MM) and is 37 years older than previous cases, highlighting that SPA does not occur exclusively in young patients as described. Immunohistochemistry revealed expression of pankeratin, CAM 5.2, CK7, CK903, Ber-EP4, vimentin, S100, and CEA and virtually no expression of CK5/6, CK20, calretinin, thrombomodulin, or glypican 3. Expression of adjacent nonneoplastic tunica vaginalis mesothelium was assessed in this patient and additional specimens. Profiles of paratesticular SPA and MM were summarized and compared with paratesticular mesothelium. Nontumoral stromal and entrapped mesothelial expression were 2 diagnostic pitfalls in this case that have not been previously described. Based on these data, a panel of markers and the use of sections containing nonneoplastic mesothelium to facilitate interpretation is recommended.

Paracortical axillary sentinel lymph node ectopic breast tissue

Benign glandular inclusions in axillary lymph nodes are uncommon, and their presence in axillary sentinel lymph nodes is exceptionally rare. The possibility of over-staging due to misinterpretation of glandular inclusions as metastatic carcinoma is a concerning issue. We present a 54-year-old female with high grade ductal carcinoma in-situ undergoing simple mastectomy with sentinel lymph node biopsy. Permanent sections of the sentinel lymph node revealed scarce naked small glands without surrounding stroma scattered in the paracortex in the superficial level. Deeper levels showed glands spanning a much larger area (2mm), with bland ducts and tubules separated by abundant stroma. The myoepithelial layer was visible and was immunohistochemically confirmed. A final diagnosis of benign ectopic breast tissue within an axillary sentinel lymph node was rendered. Previous studies described axillary sentinel lymph nodes with glandular inclusions separated by stroma or subcapsular in location. It has been suggested that paracortical location and absence of stroma are characteristics of metastasis. As demonstrated in our report, benign inclusions may be paracortical and lack surrounding stroma. We recommend that glandular inclusions should be a diagnostic consideration for cases in which paracortically located naked glands do not histologically resemble the corresponding primary tumor.

Localized amyloidosis of the nasal and paranasal mucosa: a rare pathology

Localized amyloidosis of the nasal and paranasal mucosa: a rare pathology Aaron N. Pearlman, MD⁎, Jill S. Jeffe, MD, Debra L. Zynger, MD, Anjana V. Yeldandi, MD, David B. Conley, MD Department of Otolaryngology—Head and Neck Surgery, Northwestern University, Feinberg School of Medicine, Chicago, IL, USA Department of Pathology, Northwestern University, Feinberg School of Medicine, Chicago, IL USA Received 16 September 2008