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- Anlauf, Martin, et al.
(author)
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Primary lymph node Gastrinoma or occult duodenal microgastrinoma with lymph node Metastases in a MEN1 patient - The need for a systematic search for the primary tumor
- 2008
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In: American Journal of Surgical Pathology. - 0147-5185 .- 1532-0979. ; 32:7, s. 1101-1105
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Journal article (peer-reviewed)abstract
- Gastrinoma tissue has been found frequently in lymph nodes located near the duodenum without a known primary tumor. Therefore, it has been suggested that a primary lymph node gastrinoma exists. We report on a 38-year-old woman suffering from multiple endocrine neoplasia type 1 (MEN 1) confirmed by menin gene mutation analysis. MEN1 disease started with primary hyperparathyroidism followed by Cushing disease, the detection of tumors of the pituitary, adrenal cortex, and the pancreas and also an elevated serum gastrin level. An octreotide scan revealed 4 tumors in the upper abdomen. A selective arterial calcium stimulation test located the source of the hypergastrinemia to the area of the gastroduodenal and the superior mesenteric arteries. Total pancreatoduodenectomy was performed and conventional histopathologic examination revealed a well-differentiated cystic neuroendocrine tumor of the pancreas expressing glucagon and accompanied by several microadenomas. In addition, 3 suprapancreatic lymph nodes with gastrin-positive endocrine tissue were found. None of the pancreatic microadenomas expressed gastrin and no duodenal endocrine tumor was found despite careful macroscopic examination. Only after complete embedding of the duodenal and pancreatic tissue in 65 paraffin blocks, 2 microgastrinomas (0.45 and 0.8 mm in diameter) were identified in the duodenum. It is concluded that duodenal gastrinomas that give rise to lymph node metastases may be so tiny that they are easily overlooked in a routine examination and that systematic tissue monitoring is required to identify them.
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- Downs-Kelly, Erinn, et al.
(author)
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The utility of fluorescence in situ hybridization (FISH) in the diagnosis of myxoid soft tissue neoplasms
- 2008
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In: American Journal of Surgical Pathology. - 1532-0979. ; 32:1, s. 8-13
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Journal article (peer-reviewed)abstract
- Diagnosing myxoid soft tissue neoplasms can be challenging because of overlapping histologic features. Distinct chromosomal translocations have been identified in several myxoid sarcomas, including t(12;16)(q13;p11) FUS-DDIT3 in myxoid liposarcoma, t(7,-16)(q34;p11) FUS-CREB3L2 in low-grade fibromyxoid sarcoma, and t(9;22)(q31;q12) EWSRINR4A3 in extraskeletal myxoid chondrosarcoma. These recurrent chromosomal alterations are attractive targets for diagnostic studies. To that end, dual-color, break-apart fluorescence in situ hybridization (FISH) probes spanning the genomic regions of EWSRI (22q12), DDIT3 (12q13), and FUS (16p11) (Vysis, Downer's Grove, IL) were evaluated in formalin-fixed, paraffin-embedded tissues from myxoid neoplasms, including intramuscular myxoma (it 10), myxoid liposarcoma (n = 18) low-grade fibromyxoid sarcoma (n = 10), extraskeletal myxoid chondrosarcoma (n = 13), and myxofibrosarcoma (n = 8). Of the myxoid liposarcomas, 18/18 cases had a rearrangement of the DDIT3 gene, with 17/18 (94.4%) showing both DDIT3 and FUS gene rearrangements. A FUS gene rearrangement was identified in 7/10 (70%) of lowgrade fibromyxoid sarcomas, with no changes involving EWSRI or DDIT3. An EWSRI translocation was seen in 6/13 (46.2%) of extraskeletal myxoid chondrosarcomas, without changes in DDIT3 or FUS genes. The remaining neoplasms studied showed no rearrangements involving DDIT3, FUS, or EWSRI genes. In conclusion, interphase FISH using DDIT3 and FUS probes identifies the characteristic translocation in myxoid liposarcoma. FUS and EWSRI probes are useful in confirming the diagnosis of low-grade fibromyxoid sarcoma and extraskeletal myxoid chondrosarcoma, respectively. The specificity of the probes is documented as none of the non-translocation-associated myxoid tumors showed genomic abnormalities with the probes tested. FISH is capable of providing specific ancillary information useful in this often difficult differential diagnosis.
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- Fadare, Oluwole, et al.
(author)
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Lobular intraepithelial neoplasia [lobular carcinoma in situ] with comedo-type necrosis - A clinicopothologic study of 78 cases
- 2006
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In: American Journal of Surgical Pathology. - : Ovid Technologies (Wolters Kluwer Health). - 0147-5185 .- 1532-0979. ; 30:11, s. 1445-1453
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Journal article (peer-reviewed)abstract
- The recent finding that lobular, and not ductal intraepithelial neoplasia (DIN) displays loss of E-cadherin expression has greatly facilitated the categorization of a large proportion of morphologically ambiguous intraepithelial neoplasias into ductal or lobular types. One reason for such morphologic ambiguity is the presence of comedo-type necrosis within an intraepithelial lesion that otherwise shows archetypal cytologic and architectural features of lobular intraepithelial neoplasia (LIN). The clinicopathologic features of 18 such cases are described in this report. These 18 cases of classic LIN were accumulated from the recent databases of 6 institutions. All cases, by definition, showed no expression of E-cadherin. The 18 patients, all women, were 41 to 85 years of age (mean 61.3). The lesions were initially identified in an excisional biopsy or mastectomy in 12 cases and in an incisional/core biopsy in the remaining 6 cases. An associated invasive carcinoma was present in 12 (67%) of 18 cases (7 classic lobular, 1 pleomorphic lobular, 1 ductal, 1 mixed lobtilar and ductal, 1 tubular, and 1 case with ductal and lobular carcinomas as separate foci). The average age of the 6 patients with pure LIN (ie, LIN without an invasive component (62.5 y) was not significantly different from the 12.
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- Gill, Anthony J, et al.
(author)
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Loss of nuclear expression of parafibromin distinguishes parathyroid carcinomas and hyperparathyroidism-jaw tumor (HPT-JT) syndrome-related adenomas from sporadic parathyroid adenomas and hyperplasias.
- 2006
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In: American Journal of Surgical Pathology. - : Ovid Technologies (Wolters Kluwer Health). - 0147-5185 .- 1532-0979. ; 30:9, s. 1140-9
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Journal article (peer-reviewed)abstract
- Parathyroid carcinoma is notoriously difficult to diagnose with confidence in borderline cases. Commonly there is a long lag time between diagnosis and clinical evidence of malignant behavior even in histopathologically straightforward lesions. There is therefore a need for a novel adjunctive marker to assist in the diagnosis of carcinoma. Parafibromin is the protein encoded by the putative tumor suppressor gene HRPT2. Mutations predicted to inactivate parafibromin were first detected in the germline of patients with hyperparathyroidism-jaw tumor (HPT-JT) syndrome. Subsequently, somatic mutations have been identified in the majority of sporadic carcinomas. We performed immunohistochemistry for parafibromin on 115 parathyroid tissues comprising 4 HPT-JT-related tumors (3 adenomas and 1 carcinoma), 11 sporadic parathyroid carcinomas, 79 sporadic adenomas, 3 multiple endocrine neoplasia 2A-related adenomas, 2 sporadic primary hyperplasias, 2 multiple endocrine neoplasia (MEN)-1-related hyperplasias, 6 secondary hyperplasias, 4 tertiary hyperplasias, and 4 normal parathyroid glands. There was complete absence of nuclear staining in 3 of 4 (75%) HPT-JT-related tumors and 8 of 11 (73%) sporadic parathyroid carcinomas and focal weak staining in 1 of 4 HPT-JT tumors and 2 of 11 sporadic parathyroid carcinomas. Only 1 parathyroid carcinoma exhibited diffuse strong nuclear expression of parafibromin. In contrast, 98 of 100 non-HPT-JT-related benign parathyroids showed diffuse strong nuclear positivity and 2 of 100 showed weak positive staining. We conclude that, in the correct clinical and pathologic context, complete absence of nuclear staining for parafibromin is diagnostic of parathyroid carcinoma or an HPT-JT-related tumor.
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- Horn, Lars-Christian, et al.
(author)
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Immunostaining for p16(INK4a) used as a conjunctive tool improves interobserver agreement of the histologic diagnosis of cervical intraepithelial neoplasia
- 2008
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In: American Journal of Surgical Pathology. - 1532-0979. ; 32:4, s. 502-512
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Journal article (peer-reviewed)abstract
- The quality of cervical histopathology is critical to cervical cancer prevention, cancer treatment, and research programs. On the basis of the histology results further patient management is determined. However, the diagnostic interpretation of histologic hematoxylin-eosin (H&E)-stained slides is affected by substantial rates of discordance among pathologists. Overexpression of the cyclin-dependent kinase inhibitor p16(INK4a), a cell cycle regulating protein, has been shown to be strongly correlated with dysplastic lesions of the cervix uteri. In this study.. we assessed whether p16(INK4a) immunohistochemistry may increase the performance of pathologists in diagnosing squamous lesions in cervical punch and cone biopsies. When using a consecutive p 16(INK4a)-stained slide in conjunction to the H&E-stained slide, interobserver agreement between 6 pathologists improved significantly for both cervical punch and cone biopsies (P < 0.001). For punch biopsies (n = 247), K value increased from 0.49 (moderate agreement) to 0.64 indicating substantial agreement, and interobserver agreement for cone biopsies (n = 249) improved from 0.63 (conventional H&E slide reading) to 0.70 when H&E-stained slides were read conjunctively with p16(INK4a)-stained slides. In comparison to a common consensus diagnosis established by 3 independent experts, 4 pathologists reached an improvement with the conjunctive p16(INK4a) test, 2 of them showing significantly better agreement (P < 0.001 and P = 0.002, respectively). P-16INK4a immunohistochemistry as an adjunct to conventional H&E-stained specimens thus contributes to a more reproducible diagnosis of cervical intraepithelial neoplasia, and may be a valuable aid for the interpretation of cervical histology.
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- Kutzner, H., et al.
(author)
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CD123-positive plasmacytoid dendritic cells in primary cutaneous marginal zone b-cell lymphoma : Diagnostic and pathogenetic implications
- 2009
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In: American Journal of Surgical Pathology. - 0147-5185 .- 1532-0979. ; 33:9, s. 1307-1313
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Journal article (peer-reviewed)abstract
- The histogenesis of primary cutaneous marginal zone B-cell lymphoma (PCMZL) has not yet been clarified. Plasmacytoid dendritic cells (PDC) play a crucial role in the initiation of immune responses and activation of T-cells and B-cells. We analyzed the presence of PDC by immunohistochemistry in various forms of primary cutaneous B-cell lymphomas and in B-cell pseudolymphomas. Clusters of CD123 PDC were observed in all PCMZL (23 of 23 cases; 100%) and in two-thirds of cutaneous B-cell pseudolymphomas (14 of 22; 64%), but only in a minority of primary cutaneous follicle center lymphoma (4 of 31; 13%) and not in primary cutaneous diffuse large B-cell lymphoma, leg type. CD123+ PDC clusters were found in close proximity to monoclonal plasma cells and T-cells and were already present at high numbers in early lesions and initial recurrences of PCMZL. In conclusion, the detection of larger clusters of PDC in PCMZL provides a useful adjunctive diagnostic marker and suggests a pathogenetically relevant role of these cells in PCMZL. Furthermore, the occurrence of PDC could explain the high number of T-cells typically found in PCMZL. We propose considering PCMZL as a unique and potentially antigen-driven neoplasm with PDC, T-cells, and B-cells as the constitutive tumor components. Copyright © 2009 by Lippincott Williams & Wilkins.
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