September 2004


ANATOMIC PATHOLOGY

 Antimony concentrations in nodal tissue can confirm sentinel node identity

Scolyer RA, Thompson JF, Li LX, Beavis A, et. al.


The sentinel node biopsy procedure is a highly accurate method of staging patients with cutaneous melanoma and the tumor-harboring status of sentinel nodes is the most important prognostic factor. For the procedure to provide accurate prognostic information, however, it is essential that 'true' sentinel nodes are removed and examined thoroughly. A technique to confirm sentinel node identity may reduce the false-negative rate of the procedure. The authors have found that antimony (originating from the antimony sulfide colloid used for preoperative lymphoscintigraphy in authorsinstitution) can be measured in tissue sections of sentinel nodes using inductively coupled plasma mass spectrometry. The aims of this study were to determine whether antimony concentrations can be used to confirm that removed sentinel nodes are 'true' sentinel nodes and to differentiate sentinel nodes from nonsentinel nodes. In all, 24 patients who had both a tumor-positive sentinel node and a tumor-negative nonsentinel node removed from one regional node field during the same operation, were identified. Tissue sections (50 microm) thick were cut from archival paraffin blocks of each of the sentinel nodes and nonsentinel nodes. Antimony concentrations in the tissue sections were measured using inductively coupled plasma mass spectrometry. The median and mean concentrations of antimony in parts per billion were 0.526 and 1.198, respectively (range 0.020-7.596) in the sentinel nodes, and 0.043 and 0.123 (range 0-0.800) in the nonsentinel nodes (P=0.004). In four of the 24 pairs, both the presumed sentinel nodes and the nonsentinel nodes had very low antimony levels (less than 0.18 parts per billion), suggesting that nodes designated as sentinel nodes may not have been 'true' sentinel nodes. It is concluded that determination of antimony concentrations within sentinel nodes using the highly sensitive method of inductively coupled plasma mass spectrometry can confirm the identity of sentinel nodes and validate the sentinel node technique.

Mod Pathol. 2004 Oct; 17(10): 1191-7.

  

Frozen section diagnosis for axillary sentinel lymph nodes: the first six years

Mitchell ML.

Intraoperative frozen section of axillary lymph nodes for the detection of metastatic breast cancer has been controversial because of the labor-intensive techniques necessary to obtain a highly sensitive test, and because of the uncertain significance of frequently detected submicrometastatic carcinoma. In total, 874 consecutive axillary sentinel lymph node cases examined by intraoperative frozen section over a 6-year period were reviewed retrospectively. Frozen section had a sensitivity of 60% and was 100% specific, but when cases with submicrometastatic tumor cells were considered negative, the sensitivity rose to 83%. Rare cases were called 'atypical' on frozen section; almost all of these cases were negative for carcinoma on permanent sections.

 Mod Pathol. 2004 Sep 10

  

Pathological work-up of sentinel lymph nodes in breast cancer. Review of current data to be considered for the formulation of guidelines

Cserni G, Amendoeira I, Apostolikas N, Bellocq JP


Controversies and inconsistencies regarding the pathological work-up of sentinel lymph nodes (SNs) led the European Working Group for Breast Screening Pathology (EWGBSP) to review published data and current evidence that can promote the formulation of European guidelines for the pathological work-up of SNs. After an evaluation of the accuracy of SN biopsy as a staging procedure, the yields of different sectioning methods and the immunohistochemical detection of metastatic cells are reviewed. Currently published data do not allow the significance of micrometastases or isolated tumour cells to be established, but it is suggested that approximately 18% of the cases may be associated with further nodal (non-SN) metastases, i.e. approximately 2% of all patients initially staged by SN biopsy. The methods for the intraoperative and molecular assessment of SNs are also surveyed.

 Eur J Cancer. 2003 Aug; 39(12): 1654-67.

 

 Cervical Lymphadenopathy, Fever and Leukopenia (Histiocytic-Necrotizing Lymphadenitis or Kikuchi Disease)

Kikuchi, Masahiro MD; Ohshima, Koichi MD


Kikuchi disease or histiocytic necrotizing lymphadenitis is associated with the following characteristic clinical features: appearance in adolescence, a preference to females, cervical lymphadenopathy, leukopenia with a few atypical lymphocytes, fever over 38[degrees]C, skin rashes, spontaneous regression within several months and rare recurrence. Histopathologically, the disease demonstrates distinctive features, such as a focal, partial, or diffuse involvement of the neck lymph nodes with accumulation of transformed lymphocytes, immunoblasts, plasmacytoid dendritic cells, histiocytes, either with or without phagocytosis, and the presence of apoptotic cells in the paracortex or cortex. The absence of neutrophils, eosinophils, and plasma cells in the affected foci is noticeable. Necrotic changes and appearance of foamy histiocytes are occasionally seen in these lymph nodes. The cells in the affected areas consist of CD8-positive cells with high proliferation activity and apoptotic changes, CD4- and MPO-positive cells and histiocytes, indicating a general enhancement of apoptotic activity. Similar histopathological changes are noticed in other organs, such as the skin and bone marrow. These findings indicate that Kikuchi disease is not a disease of the lymph node but rather a generalized disease. The activated apoptotic activity and proliferation of lymphoid cells in affected foci suggest a viral origin of the disease, although this has not been confirmed yet.

Pathology Case Reviews. 9(5): 199-205, September/October 2004.

 

 One Patient, Two Lymphomas

Simultaneous Primary Gastric Marginal Zone Lymphoma and Primary Duodenal Follicular Lymphoma

  Zuoqin Tang, MD, Wen Jing, MD, Neal Lindeman, MD

 Authors report the case of a 73-year-old man who presented with a 2- to 3-month history of epigastric discomfort and guaiac-positive stool. An upper gastrointestinal endoscopy revealed a diffuse erythematous nodular mucosa and submucosal thickening in the stomach. Diffuse mucosal nodularity was also found in the second portion of the duodenum. A complete workup with histologic, immunohistochemical, and molecular studies revealed 2 distinct, apparently unrelated lymphomas, namely, a gastric marginal zone B-cell lymphoma (mucosa-associated lymphoid tissue type) in a background of Helicobacter pylori gastritis and a grade 1/3 duodenal follicular lymphoma. The patient was then treated with an H pylori eradication regimen. No therapy was given for his duodenal follicular lymphoma because his symptoms were thought to be due to the gastric disease and because the duodenal lesion was small. A 6-month follow-up with upper gastrointestinal endoscopy revealed only focal biopsy scarring in the stomach and an apparently normal duodenum. The follow-up biopsies revealed significant regression of his mucosa-associated lymphoid tissue lymphoma, but persistence of his duodenal follicular lymphoma. The combination of these 2 lymphomas in the same patient and the different clinical responses to antibiotic treatment make this case unique.

 Archives of Pathology and Laboratory Medicine: Vol. 128, No. 9, pp. 10351038.



OCT4: A Novel Biomarker for Dysgerminoma of the Ovary

 Cheng, Liang MD, Thomas, Antoinette MD

The prognosis and therapy for dysgerminomas are different from those of other ovarian tumor types, making accurate diagnosis imperative for patient care. OCT4 (POU5F1) is a transcription factor involved in the regulation of pluripotency during embryonic development. It can be detected in both pluripotent cells and other early germ cells. This study examines the expression of OCT4 in both dysgerminoma and nondysgerminomatous neoplasms involving the ovary. Formalin-fixed, paraffin-embedded cell blocks of 33 cases of dysgerminoma including 2 cases of gonadoblastoma associated with dysgerminoma and 3 cases of metastatic dysgerminoma, and 111 cases of nondysgerminomatous neoplasms involving the ovary were stained using the antibody against OCT4. All cases of dysgerminomas and gonadoblastomas were positive for OCT4 with strong nuclear staining. More than 90% of dysgerminoma cells in each case showed diffuse strong nuclear staining. In addition, 3 metastatic dysgerminomas also showed uniform strong nuclear staining. All nondysgerminomatous tumors (mature teratoma, 14; yolk sac tumor, 4; Sertoli-Leydig cell tumor, 15; granulosa cell tumor, 22; Brenner tumor, 3; carcinoid tumor, 4; struma ovarii, 2; fibroma, 5; thecoma, 1; serous adenocarcinoma, 5; endometrioid adenocarcinoma, 4; small cell carcinoma, 6; stromal sarcoma, 1; malignant lymphoma, 6; metastatic malignant melanoma, 1; metastatic carcinoid, 2; metastatic small cell carcinoma, 1; and metastatic lobular carcinoma of the breast, 1) were negative for OCT4, except for some cases of clear cell adenocarcinoma of the ovary. Four of 14 clear cell adenocarcinomas showed focal positive nuclear immunoreactivity for OCT4. OCT4 is a sensitive and relatively specific biomarker for the detection of dysgerminoma. It may also be useful in the diagnosis of gonadoblastoma, which contains similar cells and may be associated with dysgerminoma. OCT4 may aid in the detection of small foci of metastatic dygerminoma in extraovarian sites and may also help distinguish dysgerminoma from other primary and metastatic tumors of the ovary.

 American Journal of Surgical Pathology. 28(10): 1341-1346, October 2004

 

The Value of Immunohistochemistry in Atypical Cutaneous Fibrous Histiocytoma

 Wilk M, Zelger BG, Nilles M, Zelger B.


Atypical cutaneous fibrous histiocytoma(ACFH)is a rare variant of dermatofibroma/fibrous histiocytoma characterized by striking atypia, thus resembling atypical fibroxanthoma. Authors studied 9 examples of ACFH histopathologically and immunohistochemically to investigate the nature of these atypical cells.Histology revealed ill-defined skin nodules, which were polypoid in 6 cases. A minority of mononuclear and giant cells (< 5%) revealed striking pleomorphism and showed large nuclei with prominent nucleoli. Immunohistologically, the atypical cells expressed vimentin, but were negative for S-100 protein, the keratin marker MNF116, alpha smooth muscle actin, CD34, factor XIIIa, and monocyte/macrophage markers Ki-M1p, KP1 (CD68), and MAC387. Positivity for MiB1 was very modest (< 1%) and limited to small- and medium-sized, inconspicuous cells. Multinucleate giant cells proved to be heterogenous, on one hand cells with differentiation toward macrophages with positivity for Ki-M1p and KP1, on the other toward fibroblasts positive for vimentin only. These immuno-histochemical results for differentiation markers in atypical cutaneous fibrous histiocytoma are similar to our previous findings and data in atypical fibroxanthoma; MiB1 helps to separate these entities from each other as the latter shows a very high proportion of proliferative atypical cells corresponding to the numerous mitoses seen in routine sections.

 Am J Dermatopathol. 2004 Oct; 26(5): 367-371.

   

CYTOPATHOLOGY

 Psammoma Bodies in Cervicovaginal Smears: Significance and Practical Implications for Diagnostic Cytopathology

Fadare, Oluwole MD; Chacho, Mary S MD; Parkash, Vinita MD


The traditional association of psammoma bodies with some malignancies of the gynecologic tract raises potentially significant management difficulties when such bodies are identified on routine cervicovaginal smears. This review summarizes the reported cases of psammoma bodies identified on cervicovaginal smears in the world literature (a total of 140 cases, 113 (81%) of which had sufficient clinicopathologic information). Authors conclusions are as follows: (1) The finding of psammoma bodies in this setting is distinctly unusual with an incidence of less than 0.001% on consecutively screened smears. (2) On consecutively screened smears, patients with psammoma bodies have an associated malignancy or ovarian borderline tumor 0-22.7% of the time, depending on the series; this figure climbs to 38% when all the case reports and small series in the literature are included. (3) The most reliable predictor of a malignancy in these patients is the finding of cells on the smear that by themselves are diagnostic of malignancy on cytologic grounds. (4) Other factors that, on a purely statistical basis, appear to increase the likelihood of a synchronous or metachronous malignancy or borderline tumor include an older age at diagnosis and/or clinical presentations such as postmenopausal bleeding. (5) When 1 or more psammoma bodies are identified on a cervicovaginal smear, this finding should not be ignored and should generate some clinical investigation to identify its source.

 Advances in Anatomic Pathology. 11(5): 250-261, September 2004.

  

MICROBIOLOGY

 Bacteria Tied to Chron's Disease

 Research published in The Lancet gives evidence that implicates Mycobacterium avium paratuberculosis (MAP) infection as a cause of Crohn's disease. The study used a novel approach to investigate this link between bacteria and the disease.

Researchers said that viable MAP was detected in half of the patients with Crohn's disease, but in none of the control subjects lacking inflammatory bowel disease. This finding alone does not prove that MAP is a causative agent; however, it suggest that larger-scale studies will follow.

Researchers tested for MAP in blood samples from 28 patients with Crohn's disease, 9 with ulcerative colitis, and 15 without inflammatory bowel disease. Fourteen patients with Crohn's disease had specimens that grew viable MAP in culture. Only 2 ulcerative colitis patients cultured positive for MAP, and no control subjects cultured MAP.

In a related editorial in The Lancet, Dr. Warwick S. Selby, from the University of Sydney in Australia, comments, "whatever one's view, MAP cannot continue to be ignored in Crohn's disease. Funding bodies and laboratory and clinical researchers must clarify with some urgency, once and for all, whether this organism is important in Crohn's disease or is merely a curious bystander."

 American Journal of Clinical Pathology, Sept. 19 2004

  

Unrecognised tuberculosis in HIV-infected patients: sputum culture is a useful tool

Swaminathan S, Paramasivan CN, Kumar SR, Mohan V, Venkatesan P.


Diagnosis of tuberculosis is challenging, especially in human immunodeficiency virus (HIV) positive persons who may have atypical clinical and radiographic features. We report the isolation of Mycobacterium tuberculosis from sputum samples of 10 (4%) HIV-positive persons who were asymptomatic with normal chest radiographs and negative sputum smears for acid-fast bacilli. Six of them had strongly positive tuberculin reactions while four were severely immunosuppressed. Authors observation highlights the utility of routine sputum culture in the diagnosis of tuberculosis in high-risk individuals.

Int J Tuberc Lung Dis. 2004 Jul;8(7): 896-8.


 Enhanced Culture Detection of Kingella kingae, a Pathogen of Increasing Clinical Importance in Pediatrics

Gene A, Garcia-Garcia JJ, Sala P, Sierra M, Huguet R.


Osteoarticular infection and occult bacteremia are the 2 invasive infectious pathologies most frequently associated in childhood with Kingella kingae. Authors report a series of 11 patients in whom osteomyelitis predominates over septic arthritis, which is the reverse of other series, probably as a consequence of inoculation of samples during surgery on agar media, used in combination with or as an alternative to inoculation into blood culture bottles. Although K. kingae infections usually follow a benign clinical course, authors noted 2 patients with mild orthopedic sequelae.
 

Pediatr Infect Dis J. 2004 Sep; 23(9): 886-888.

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