Immunopathology of Kikuchi-Fujimoto disease: A reappraisal using novel immunohistochemistry markers.

AIMS: Kikuchi-Fujimoto disease (KFD) is a self-limited disease characterised by destruction of the lymph node parenchyma. Few studies have assessed the immunohistological features of KFD, and most employed limited antibody panels that lacked many of the novel immunohistochemistry markers currently available. METHODS AND RESULTS: We used immunohistochemistry to reappraise the microanatomical distribution of plasmacytoid dendritic cells (pDCs), follicular helper T cells and cytotoxic T cells, B cells, follicular dendritic cell (FDC) meshworks, and histiocytes in lymph nodes involved by KFD. The study group consisted of 138 KFD patients (89 women; 64.5%) with a median age of 27 years (range, 3-50 years). Cervical lymph nodes were most commonly involved, in 108 (78.3%) patients. The numbers of pDCs were increased, predominantly around and within apoptotic areas and the paracortex, and tapering off within xanthomatous areas. pDCs formed sizeable tight clusters, most notably around apoptotic/necrotic areas. T cells consisted mostly of CD8-positive cells with predominant expression of T-cell receptor-ß. There were notable increases in the numbers of CD8-positive T cells within lymphoid follicles, and their numbers correlated with alterations in FDC meshworks (P < 0.001). The number of follicular helper T cells was decreased within distorted FDC meshworks. CD21 highlighted frequent distortion of FDC meshworks, even in lymph node tissue that was distant from apoptotic/necrotic areas. Distorted FDC meshworks spanned all morphological patterns, and FDC meshwork characteristics (intact; distorted; remnant/nearly absent) correlated with morphological patterns (P < 0.01). CONCLUSIONS: The immunohistological landscape of KFD is complex and characterised by increased numbers of pDCs that frequently cluster around apoptotic/necrotic foci, increased numbers of cytotoxic T cells, and substantial distortion of FDC meshworks.

BRAF analysis on a spectrum of melanocytic neoplasms: an epidemiological study across differing UV regions.

BRAF mutation has been linked to the development of melanocytic tumors in homogeneous Caucasian cohorts. The role of solar UV radiation (UVR) in BRAF mutation status is poorly understood. We studied the epidemiology of BRAF mutation across a spectrum of melanocytic neoplasms in populations with differing UVR rates. Extended testing for 9 mutation types was attempted on 600 melanocytic neoplasms including banal nevi (n = 225), dysplastic nevi (n = 113), primary (n = 172), and metastatic melanomas (n = 90). Specimens were collected from 4 countries with increasing UVR rates (in kJ/m/yr): Syria (n = 45; UVR = 93.5), Lebanon (n = 225; UVR = 110), Pakistan (n = 122; UVR = 128), and Saudi Arabia (n = 208; UVR = 139). UVR was estimated from 21-year averages from The National Center for Atmospheric Research database. The overall BRAF mutation rate was 49% (268 of 545) and differed significantly by the geographic location [34% Pakistan, 49% Lebanon, 67% Syria, and 54% Saudi Arabia; P = 0.001], neoplasm type (P < 0.001), and anatomical location (P < 0.001) but not with age (P = 0.07) and gender (P = 1.0). V600E was the predominant mutation type, found in 96.3% of the cases. Incidence of melanoma was significantly greater in BRAF-negative (39%) versus BRAF-positive (17%) groups. For BRAF-positive cases, less severe lesions were systematically more frequent (P < 0.001). Multivariate analysis indicated that BRAF mutation is predicted by neoplasm type, anatomical site, and geographic location. In our Near East cohort, BRAF mutation rates varied by geographic location but not based on UVR. BRAF-positive status was associated with less severe lesions.

Longevity of Immunoglobulin-G Antibody Response Against Nucleocapsid Protein Against SARS-CoV-2 Among Healthcare Workers.

Background: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused the latest pandemic and the most significant challenge in public health worldwide. Studying the longevity of naturally developed antibodies is highly important clinically and epidemiologically. This paper assesses the longevity of antibodies developed against nucleocapsid protein amongst our health-care workers. Methods: This longitudinal cohort study was conducted at a tertiary hospital, Saudi Arabia. Anti-SARSsCoV-2 antibodies were tested among health-care workers at three-point intervals (baseline, eight weeks, and 16 weeks). Results: Of the 648 participants, 112 (17.2%) tested positive for Coronavirus (COVID-19) by PCR before the study. Of all participants, 87 (13.4%) tested positive for anti-SARS-CoV-2 antibodies, including 17 (2.6%) participants who never tested positive for COVID-19 using rt-PCR. Out of the 87 positive IgG participants at baseline, only 12 (13.7%) had remained positive for anti-SARS-CoV-2 antibodies by the end of the study. The IgG titer showed a significant reduction in values over time, where the median time for the confirmed positive rt-PCR subgroup from infection to the last positive antibody test was 70 (95% CI: 33.4-106.5) days. Conclusion: Health-care workers are at high risk of exposure to the SARS-CoV-2 virus, and contracting an asymptomatic infection is not unlikely. Developing and sustaining natural immunity differs from one person to another, while the rate of positive IgG anti-SARS-CoV-2 wanes over time. Clinicaltrialsgov Identifier: NCT04469647, July 14, 2020.

Immunotactoid glomerulopathy: clinicopathologic and proteomic study.

BACKGROUND: Immunotactoid glomerulopathy (ITG) is a rare glomerular disease. Here, we report the largest clinicopathologic series of ITG and define its proteomic profile. METHODS: The characteristics of 16 ITG patients who were identified from our pathology archives are provided between 1993 and 2011. We also performed laser microdissection and mass spectrometry (LMD/MS) in three cases. RESULTS: Presentation included proteinuria (100%), nephrotic syndrome (69%), renal insufficiency (50%) and microhematuria (80%). Hypocomplementemia was present in 46% and a serum M-spike in 63%. Hematologic malignancy was present in 38%, including chronic lymphocytic leukemia in 19%, lymphoplasmacytic lymphoma in 13% and myeloma in 13%. The pattern of glomerular injury was membranoproliferative (56%), membranous (31%) or proliferative (13%) glomerulonephritis. The microtubular deposits were immunoglobulin light chain restricted in 69% and had a mean diameter of 31 nm (range 17-52). During an average of 48 months of follow-up for 12 patients, 50% had remission, 33% had persistent renal dysfunction and 17% progressed to end-stage renal disease. Proteomic analysis by LMD/MS revealed the presence of immunoglobulins, monotypic light chains, complement factors of the classical and terminal pathway and small amount of serum amyloid P-component. CONCLUSIONS: Hematologic malignancy, particularly lymphoma, is not uncommon in ITG. ITG appears to have a better prognosis than other paraprotein-related renal lesions, with a half of patients expected to recover kidney function with immunosuppressive therapy or chemotherapy. The proteomic profile of ITG is consistent with deposition of monotypic immunoglobulins and activation of the classical and terminal pathway of complement.

A Cohort Study of Seroprevalence of Antibodies Against SARS-CoV-2 Infection Among Healthcare Workers at a Tertiary Hospital in Saudi Arabia.

Background: The nature of the healthcare workers' jobs standing at the frontline against the coronavirus disease 2019 (COVID-19) puts them at a higher risk of unknowingly contracting the disease and potentially contributing to the spread. This study aims to assess the overall positive seroconversion prevalence of SARS-CoV-2. Methods: This is a longitudinal cohort study of healthcare workers at Johns Hopkins Aramco Healthcare (JHAH). JHAH is a tertiary hospital located in Dhahran serving patients in several districts in the Eastern Province of Saudi Arabia. Participants were recruited between June and December 2020. Each participant had a serology blood test and completed the World Health Organization's risk factor assessment questionnaire. Results: This study included 682 participants working in JHAH, representing 15.7% of our population. Out of the 682 participants, 15.2% had a positive SARS-CoV-2 rt-PCR before taking part in the study. However, only 87 tested positive for SARS-CoV-2 antibodies, a prevalence of 12.7% of all participants. Out of the 87 positives for SARS-CoV-2 antibodies, 17 participants never tested positive for COVID-19 rt-PCR, a prevalence of 2.9%. Moreover, not properly using alcohol-based hand rub or soap and water after the risk of body fluid exposure and wearing personal protective equipment when indicated were found to be statistically significant to having a positive SARS-CoV-2 IgG assay. Conclusion: Positive seroconversion rate was considerably low during the first wave of COVID-19 amongst JHAH's healthcare workers and similar to other healthcare organizations in Saudi Arabia. Seropositivity correlated significantly with following infection prevention and control recommendations. Clinicaltrialsgov Identifier: NCT04469647.

Prevalence of dermatofibrosarcoma protuberans in Saudi Arabia over 24 years.: A retrospective single-institution study.

OBJECTIVES: To conduct a descriptive clinicopathological and demographic analysis of dermatofibrosarcoma protuberans among Saudi patients attending a tertiary care center in the eastern province of Saudi Arabia. METHODS: This retrospective, single-center study reviewed the medical records and pathology reports of Saudi patients attending a tertiary center (Johns Hopkins Aramco Health Care) in Dhahran, Saudi Arabia from 1995 to 2019 to identify all cases of dermatofibrosarcoma protuberans. Demographic and phenotypic data were also analyzed. RESULTS: Thirty-five Saudi patients were identified as having dermatofibrosarcoma protuberans. Females constituted 68.6% of patients. The trunk was the most common site of involvement (54.3%), followed by the lower extremities (34.3%), upper extremities (8.6%), and head and neck (2.9%). The mean tumor size was 2.9 cm (standard deviation: ±2.0). There was only one case of distant metastasis of fibrosarcomatous dermatofibrosarcoma protuberans. CONCLUSIONS: Dermatofibrosarcoma protuberans was not frequently encountered in Saudi patients in a tertiary center that treats approximately 187,668 patients. Dermatofibrosarcoma protuberans disease patterns and demographic data were similar to those reported worldwide. Further studies are required to characterize dermatofibrosarcoma protuberans in the Saudi population.

Gastrointestinal stromal tumors. A clinicopathological study.

OBJECTIVES: To evaluate the clinical presentations and immunohistochemical (IHC) properties of gastrointestinal stromal tumors (GISTs) and to compare them to internationally published data. METHODS: Thirty-six patients diagnosed with GISTs between January 1997 and December 2015 were retrospectively studied in 2 tertiary hospitals. Immunohistochemical staining was carried out prospectively when it has not been completed fully at the beginning. Results: The median age of patients was 54 years  (range; 17-81 years). Predominantly, we found more females were affected. The male to female ratio was 1:1.7. The most frequently affected organs were the stomach (63.8%) followed by small bowel (25%) and colorectal region (8.4%). Abdominal pain was the most frequent presentation in 33.3% of the patients then gastrointestinal (GI) bleeding in 30.5%. Most of the gastric GISTs were at early stages at presentation: stage 1 and II (60.8%), while in non-gastric GISTs, the tumor stage was advanced: stage III and IV (69.3%). The IHC characteristic of GIST in descending order showed positivity for vimentin (88.9%), CD117 (83.3%), CD34 (77.8%), Ki67 (63.9%), SMA (38.9%), desmin (27.8%), and S100 (19.4%). CONCLUSION: Gastrointestinal stromal tumors in our study demonstrates a major similar feature as the published international data. However, minor differences do exist in terms of clinical features and immunohistochemistry.

Mullerianosis of the Urinary Bladder: A Case Report.

Mullerianosis is a rare entity consisting of an admixture of 2 or more of the following tissues: endometriosis, endocervicosis, and endosalpingiosis. It most commonly affects the urinary bladder and affects females of fertile age. It presents clinically as hematuria, dysuria, and pelvic pain which may be associated with menstruation. Radiologically and macroscopically, it typically presents as a polypoid mass in the dome or posterior wall of the bladder. Histologically, it consists of glands of varying size lined by endometrial, endocervical, or tubal epithelium. Mullerianosis clinically and histologically mimics other benign and malignant lesions. Herein we report a case of mullerianosis of the urinary bladder. This is a rare lesion with less than 20 cases reported in the literature thus far. We believe raising awareness of this poorly recognized entity is of utmost significance in order to avoid misdiagnosis and the following unnecessary radical procedures.

HER2, TOP2A, CCND1, EGFR and C-MYC oncogene amplification in colorectal cancer.

AIM: Recent studies had suggested substantial molecular differences between tumours from different ethnic groups. In this study, the molecular differences between the incidences of colorectal carcinoma in Saudi and Swiss populations are investigated. METHOD: 518 cases of colon cancer tumours (114 from Saudi Arabia and 404 from Switzerland) were analysed in a tissue microarray format. Fluorescence in situ hybridisation (FISH) was used to estimate frequencies of copy number changes of known oncogenes, including HER2, TOPO2A, CCND1, EGFR and C-MYC. RESULTS: Using FISH, amplifications were mostly low level (gene-to-centromere ratio 2 to 4), which is in contrast with other tumour types with more frequent gene amplifications. The amplifications were particularly frequent for MYC (Saudi 9% and Swiss 14.2%) but unrelated to clinical outcome and pathological information. Remarkably, there were four tumours exhibiting classic high-level gene amplification for HER2 (Swiss 1.3%), a pattern often accompanied by response to trastuzumab (Herceptin) in breast cancer. Occasional high-level amplifications were also observed for CCND1 (Saudi 1/106, 0.9%; Swiss 2/373, 0.5%) and EGFR (Swiss 2/355; 0.6%). CONCLUSIONS: Rare high-level amplifications of therapeutic target genes were found in patients with colon cancer. Although no molecular differences were found between incidences of colon cancer cases in Swiss and Saudi populations, these observations emphasise the urgent need for clinical studies investigating the effect of targeted therapies.

Prevalence of fragile histidine triad expression in tumors from saudi arabia: a tissue microarray analysis.

AIM: The fragile histidine triad (FHIT) gene was discovered and proposed as a tumor suppressor gene for most human cancers. It encodes the most active common human chromosomal fragile region, FRA3B. We studied the prevalence of loss of FHIT expression in various tumors and correlated its loss with various clinicopathologic features. METHODS: To determine whether the absence of FHIT expression correlates with clinical variables such as grade, stage, and survival time, we assessed FHIT expression using immunohistochemistry. More than 1,800 tumors from more than 75 tumor categories were analyzed by immunohistochemistry in a tissue microarray format. RESULTS: Loss of FHIT expression ranged from 19% in ovarian tumors to 67% in lung cancers. Clinical and pathologic features like grade, stage, tumor size, and lymph node metastasis showed correlation with loss of FHIT expression in some tumors. No difference was seen in the survival patterns and loss of FHIT expression in any of the tumor groups studied. CONCLUSIONS: Loss of FHIT expression is an ubiquitous event in the multistep, multifactorial carcinogenesis process. FHIT may be altered at different stages in different types of cancers. Most of the tumors with a wider prevalence of loss of FHIT expression as an early event show a correlation with clinicopathologic features. However, in some of the tumors, FHIT expression is lost as a late event and is only seen in a fraction of the tumors.

Hodgkin's lymphoma with concurrent systemic amyloidosis, presenting as acute renal failure, following lymphomatoid papulosis.

BACKGROUND: Hodgkin's lymphoma (HL) has been reported to occur infrequently in association with lymphomatoid papulosis (LP). On the other hand, amyloidosis may also occur as a complication of lymphomas including HL but has never been reported in association with LP. We herein present an unusual case of a patient with LP who 3 years later developed concomitant HL, as well as kidney and brain amyloidosis, leading to nephrotic syndrome, acute renal failure, coma and death within 3 weeks. In our patient the simultaneous development of amyloidosis and HL suggests that amyloidosis is secondary to LP, an association never reported before. METHODS: A 74-year-old man with a 3-year history of LP presented with oliguria. He was found to have acute renal failure and 37 g of proteinuria. The patient had had a right nephrectomy performed 27 years before because of a small nonfunctioning kidney. He was found to have paraaortic and mesenteric lymphadenopathy that were biopsied percutaneously. Despite supportive dialysis the patient continued to do poorly, went into coma and died. RESULTS: Biopsy of his single left kidney showed enlarged glomeruli completely replaced by amyloidosis confirmed by Congo red stain and electron microscopy. His paraaortic lymph nodes exhibited classic HL with CD30- and CD15-positive Reed-Sternberg cells in a background of mixed inflammatory cells including prominent eosinophils. A CT scan of the brain was negative; however, the MRI showed multiple periventricular parenchymatous lesions and changes of cerebral amyloid angiopathy. CONCLUSION: In this case, the concomitant presentation of systemic amyloidosis and HL post-LP suggests that amyloidosis is a late sequela of LP, an association that has never been reported before.

Colorectal carcinoma from Saudi Arabia. Analysis of MLH-1, MSH-2 and p53 genes by immunohistochemistry and tissue microarray analysis.

OBJECTIVE: To document the incidence and role of p53 and DNA mismatch repair proteins in colorectal carcinomas, and to evaluate the relative frequency of major molecular pathways in colorectal cancers from Saudi Arabia. METHODS: We collected the formalin fixed, paraffin embedded tissues from 154 colorectal tumors (83 patients from King Faisal Specialist Hospital and Research Centre and 71 from Saudi Aramco Dhahran Health Centre) between January 1989 and December 2003. We analyzed the p53 and mismatch repair gene expression (hMSH-2, hMLH-1) by immunohistochemistry in tissue microarray format. RESULTS: Expression loss of at least one mismatch repair gene was found in 33.8% of cases and significantly associated with the right-sided tumor location (p=0.0047). The p53 positivity was observed in 57.5% of tumors, and was inversely linked to expression loss of mismatch repair genes (p=0.0102). CONCLUSION: The strong confirmation of the previously established associations between tumor phenotype, and mismatch repair gene alteration provided strong evidence for the validity of our experimental approach. Together with the higher incidence of right sided location in Saudi (46.6%) than in Western colon cancers (34.9%), the observed high prevalence of mismatch gene expression loss in Saudi tumors argues for a higher importance of microsatellite instability in this population. If confirmed, it will be interesting to see whether an increased level of familial or sporadic microsatellite instability cases is causing this variation.

CD10 and CD138 can be expressed in giant cell tumor of bone: An immunohistochemical study.

Giant cell tumor of bone (GCTB) is a primary bone neoplasm which is characterized by the presence of mononuclear cells (MCs) and osteoclast-like multinucleated giant cells (MNGCs). Up to our knowledge, CD10 immunoreactivity in GCTB has not yet been studied, and only one study touched on CD138 immunoreactivity in GCTB. The objective of this study is to investigate the immunoreactivity of CD10 and CD138 in GCTB. We offer a discussion of our findings in the context of the differential diagnosis, particularly in small biopsy material. We retrieved and reviewed 15 well-documented cases of GCTB from January 2008 to December 2014. Well-controlled standard immunohistochemical satins were performed on these cases for CD10 and CD138 and few other selected antibodies. Immunoreactivity for CD10 was membranous and was found in 14 (93%) cases. This immunoreactivity was found only in the MCs, whereas the MNGC were all negative. CD138 showed variable positivity in 11 (73%) while 4 (37%) were completely negative. Similar to CD10, staining for CD138 was only seen in the MC; however, the immunoreactivity was predominantly concentrated in the peri-vascular areas. Most of GCTB cases can show variable immunoreactivity for CD10 and CD138. The aforementioned immune-expression raise the possibility of a role in the pathogenesis of GCTB. Paying attention to this immunoreactivity is recommended when considering the clinical and radiological differential diagnosis, especially in small biopsy specimens.

CD44 loss in gastric stromal tumors as a prognostic marker.

BACKGROUND: The adhesion molecule CD44 (CD44s; CD44H) and its isoforms (CD44v3-6 and v9) are preferentially expressed by different cell types. These transmembrane glycoproteins are involved in cell-cell and cell-matrix interactions and in cell trafficking and, thus, may play a role in tumor metastasis and/or local invasion. The expression pattern of CD44s and variant isoforms, particularly CD44v6 and CD44v9, of some neoplasms, including soft tissue tumors, correlates with clinical course and outcome. The clinical behavior of gastrointestinal stromal tumors (GIST) is site specific; however, other reliable predictors of clinical outcome have not been identified. Thus, the prognostic value of CD44s and isoform expression in GIST were evaluated by immunohistochemistry of tissue microarrays. DESIGN: Paraffin-embedded formalin-fixed tissue cores (129: 103 GIST and 26 normal stomach smooth muscle) from 33 patients with clinical outcome data were collected and used for the construction of the tissue microarrays. One to five tissue cores from each patient specimen were evaluated (mean = 3 tissue cores/patient). Array slides were stained with anti-CD44s (CD44H) and with antibodies to v3, v4, v5, v6, and v9 isomers. CD44s and isoform expression and staining intensity were scored semiquantitatively without knowledge of patient identity or outcome: 0 = no; 1 = weak; 2 = moderate; 3 = moderate to strong; 4 = strong. The scores of multiple cores from the same GIST were averaged; the nonneoplastic smooth muscle was similarly graded. CD44s and isoform expression and intensity were compared with outcome. RESULTS: The 33 patients with gastric GIST, 0.8 to 30 cm in size, were followed for 1 to 111 months with a median follow-up of 7 months (mean 17.5 months). The overall median survival was 25 months. Nine of the 33 (27%) patients had metastases, 9 (27%) had recurrent disease, and 9 (27%) died of disease (9-111 months; mean 39 months; median 23 months). All 18 patients with GIST CD44s expression > 2+ were alive at last follow-up (1-62 months; median 3.5 months; mean 11 months). More than half (53%) of patients with GIST CD44s expression < or = 2+ died (9-111 months; median 23 months; mean 38 months); the median follow-up of the surviving patients with CD44 expression < or = 2 was 5 months (2-22 months; mean 6.5 months; log rank P = 0.07). The majority of tumors were variably positive CD44v3 and CD44v4, but there was minimal staining (number of cases and/or expression level) with antibodies directed against the v5, v6, and v9 isomers. CONCLUSION: These preliminary results suggest that although gastric GISTs variably express CD44s and variants, only the expression of CD44s correlates with clinical outcome with loss of CD44s positivity correlating with poor clinical outcome.

ANCA-associated crescentic IgA glomerulonephritis in pregnancy.

Only a few reports have documented the presence of crescentic IgA nephropathy associated with antineutrophil cytoplasmic antibodies (ANCA), suggesting an overlap that has therapeutic significance as regards the patients' response to treatment. We report a case of rapidly progressive glomerulonephritis with P-ANCA, with biopsyproven crescentic IgA glomerulonephritis in an 11-week pregnant woman who responded very well to cyclophosphamide and prednisone. Her 24-h urine protein dropped from 5400 mg/day to 516 mg/day and serum creatinine from 2.7 mg/dL to 1.4 mg/dL. To the best of our knowledge, this is the first such case reported in pregnancy. Eighteen months after her initial presentation, she has no significant clinical problems and her laboratory work-up shows stable results.

Mycotic cysts: report of 21 cases including eight pheomycotic cysts from Saudi Arabia.

BACKGROUND: Mycotic cysts are subcutaneous cystic granulomas caused by either dematiaceous (pigmented) fungi (pheomycotic cysts) or eumycotic (nonpigmented fungi) present in soil, wood, and decaying plant material. These fungi gain access to the tissues via a wooden splinter or thorn. No deep tissue involvement or extension to bone is known to occur. METHODS: We reviewed our surgical pathology files for the last 32 years. All cases with the diagnosis of cysts with fungi, thorns, or splinters and associated granulomatous and acute inflammation were reviewed. Gomori's silver and periodic acid-Schiff stains were performed in all cases. RESULTS: Twenty-one cases of mycotic cyst were found, including eight pheomycotic cysts (one with a recurrent lesion seen 11 months after the initial excision of the cyst). Thirteen cysts had nonpigmented fungal hyphae. There were 14 males and seven females, with an age range of 5-76 years. The dorsum of the foot was the most frequently affected site (12 cases). Four cases involved the fingers, two involved the knee area, two involved the big toe, and one each involved the leg, ankle, and forearm. The cysts measured 0.6-4.5 cm in diameter. Histologically, there was granulomatous inflammation with a variable degree of neutrophilic infiltrate giving central abscess formation. Twelve cases showed a wooden splinter. All cases were positive for fungal organisms, mostly septate hyphae and spores that were highlighted by special stains. Fungal pigment, ranging from yellow-brown to light brown to black, was observed in eight cases. No extension to deep tissues was noted. The clinical impression varied widely including ganglion, sebaceous cyst, giant cell tumor of the tendon sheath, and lipoma. One patient was immunosuppressed following renal transplantation. All patients were treated by simple excision. No antifungal chemotherapy was needed or administered in any of the patients. One patient had a recurrence of his lesion within 1 year as a result of inadequate initial excision. A second re-excision was curative. CONCLUSION: Mycotic cysts are uncommonly encountered lesions that can be easily missed, especially in cases with scant fungal elements, thus requiring special stains to detect the organisms. We reported 21 cases of mycotic cyst, including eight pheomycotic cysts, with emphasis on the histopathologic recognition of this unusual entity.

Acute placental infection due to Klebsiella pneumoniae: report of a unique case.

A 40-year-old woman, gravida 9, with seven healthy children and a history of one abortion (p 7 + 1), presented at 18 weeks of gestation with fever and malodorous vaginal discharge. Ultrasound revealed a macerated fetus. The placenta showed acute chorioamnionitis and acute villitis with microabscess formation. Blood and vaginal cultures both grew Klebsiella pneumoniae. This is the first reported case in English literature of Klebsiella pneumoniae causing suppurative placentitis leading to fetal demise.

Lipoadenoma: is it arising from thyroid or parathyroid? A diagnostic dilemma.

Fat-containing lesions of endocrine organs are rare. Distinguishing lipoadenomas of the thyroid gland from lipoadenomas of parathyroid glands can be challenging during intraoperative consultation. Our patient had a well-circumscribed tan-pink nodule present on the surface of the thyroid gland, exhibiting abundant fat interspersed between the cells, with ample eosinophilic cytoplasm arranged in trabeculae and solid sheets. Immunohistochemistry showed strong positivity for thyroglobulin confirming the origin of the nodule to be thyroid. Only few cases of lipoadenomas of the thyroid and parathyroid have been reported in the literature. There is considerable histologic overlap between the two, making it difficult to determine the site of origin. We briefly discuss the features that may be helpful in this distinction.

CD5-negative, CD10-negative small B-cell leukemia: variant of chronic lymphocytic leukemia or a distinct entity?

CD5- and CD10-negative chronic lymphocytic leukemias are quite uncommon as compared to the CD5-positive CLL. We reviewed 250 sequential cases of peripheral blood lymphocytosis to characterize cases of small B-cell lymphoproliferative disorders, submitted with a clinical diagnosis of chronic lymphocytic leukemia exhibiting a non-classic immunophenotypic profile. Six cases of CD5-, CD10-negative chronic lymphocytic leukemias and no tissue involvement were identified that revealed high-density surface-membrane immunoglobulin and CD20 expression, with variable expression of CD11c, CD23, and CD25. Most had a profound leukocytosis (mean WBC 180 x 10(9)/L) with proliferation of mature-appearing lymphocytes. Subsequent bone marrow biopsies showed diffuse infiltration by neoplastic cells in all evaluated patients. The clinical course appeared indolent, with follow-up revealing three patients alive (survival time 38-68 months), while two died of unrelated causes and one was lost to follow-up soon after diagnosis. These cases may represent somewhat unusual chronic lymphoproliferative disorders, with morphologic features and immunophenotypic profile not readily classifiable, but which are certainly atypical for classic chronic lymphocytic leukemia. Some of these features are reminiscent of those seen in marginal-zone lymphoma. However, it is most unusual for this known to be tissue-based disease to present primarily as leukemia rather than lymphoma.