Vascular Malformation and CAP Polyposis: A New Insight into Pathophysiology or Fortuitous Association?

INTRODUCTION: CAP polyposis is a benign colorectal process presenting with multiple colorectal polyps with a "CAP" of inflammatory granulation tissue whose etiology has remained largely unknown. CASE: A 24-year-old male presented with a long-standing history of repeated multiple sessile colonic polyps over a period of 17 years. RESULTS: The numerous polyps showed consistent histologic features of superficial erosion with a surface "CAP" of granulation tissue with minimal submucosa to evaluate over this period. A left hemicolectomy disclosed an extensive vascular malformation. CONCLUSION: The underlying vascular malformation may have an etiologic correlation to the overlying CAP polyps in this patient. Future cases may benefit from an evaluation of the underlying submucosa for the presence of possible vascular malformation likely to be missed on superficial polypectomy.

p16 Immunohistochemistry Is Not Always Required For Accurate Diagnosis of Grade 2 Squamous Intraepithelial Lesions.

OBJECTIVES: Preinvasive squamous neoplasms of the lower genital tract are currently classified using a two-tier system (high- or low-grade squamous intraepithelial lesion) as directed by the Lower Anogenital Squamous Terminology (LAST) guidelines but may also be subclassified as intraepithelial neoplasia grade 1 (-IN1), -IN2, or -IN3. The LAST recommended that all diagnoses of -IN2 be supported by immunohistochemistry (IHC) for p16. We examined whether p16 and Ki-67 IHC are necessary to diagnose -IN2 when the lesion has obvious high-grade histology. MATERIALS AND METHODS: p16 and Ki-67 IHC were performed prospectively and retrospectively on vulvar, vaginal, and cervical specimens with an initial diagnosis of -IN2 based on hematoxylin and eosin morphology, and a final diagnosis was made after consensus review. RESULTS: Five of 46 prospective and four of 38 retrospective cases were p16 negative. The diagnosis of -IN2 was maintained in eight of these nine cases because of compelling high-grade squamous intraepithelial lesion histology. Overall, p16 and Ki-67 IHC altered the -IN2 diagnosis to a lower grade in only one of 84 cases (1.2%, <0.01%-7.1%). Moreover, p16 was positive in all cases where the preanalytic impression was of -IN2/3 (13/13). CONCLUSIONS: p16 IHC lacks utility in cases of morphologically obvious -IN2, because the stain is positive in most cases. The LAST recommendation to use p16 IHC to support all diagnoses of -IN2 will result in performing the immunostain in many circumstances where it is not medically necessary. Among cases that are p16 negative, many have compelling high-grade morphology. The LAST perspective that the stain trumps histology may allow false-negative IHC results to prevail.

Intratumoral Vasculopathy in Leiomyoma Treated With Tranexamic Acid.

Although intravascular thrombi and infarct-type necrosis have been reported in leiomyomas following tranexamic acid therapy, intratumoral vasculopathy resembling acute atherosis has not been reported to date in patients without exposure to gonadotropin receptor agonist. We describe a case of intratumoral vasculopathy resembling acute atherosis in a leiomyoma in a 49-year-old woman, with hereditary hemorrhagic telangiectasia and menorrhagia, treated with tranexamic acid. The patient had no exposure to gonadotropin receptor agonists. Pathologic examination of the hysterectomy specimen showed a 5.7-cm submucosal leiomyoma containing multiple arteries with fibrinoid change accompanied with abundant subintimal foamy macrophages and occasional luminal thrombi. The vascular media showed scant lymphocytic inflammation without necrosis. The leiomyoma contained numerous mast cells and edematous areas. Vessels outside of the leiomyoma showed neither fibrinoid changes nor inflammation. The patient is alive and well with no signs of systemic vasculitis. We demonstrate that intratumoral vasculopathy resembling acute atherosis may be seen in leiomyomas from patients taking tranexamic acid and postulate that this change results in vascular thrombosis, tumoral edema, and infarct-type necrosis.

Parenchymal infiltration and lymphoma-associated membranoproliferative pattern of glomerular injury: an unusual presentation of mantle cell lymphoma.

Lymphomatous processes have been shown to involve the kidney by direct and paraneoplastic mechanisms. Direct injury can manifest by effacement of typical parenchymal architecture by the lymphomatous infiltrate, and indirect, paraneoplastic mechanisms have been associated with a variety of glomerular lesions. Mantle cell lymphoma (MCL) has rarely been reported to be associated with both direct infiltration and/ or paraneoplastic glomerular lesions. We describe a patient with rapidly progressive glomerulonephritis whose renal biopsy showed effacement of the renal parenchyma by MCL and a membranoproliferative pattern of glomerular injury. The patient's bone marrow was also involved by MCL, and serology revealed small M-spikes and a positive rheumatoid factor. The clinicopathologic findings were consistent with a membranoproliferative pattern of glomerular injury secondary to MCL with infiltrative destruction of renal parenchyma. This case is unusual in that MCL was diagnosed on renal biopsy, that there was a two-pronged mechanism of renal injury, and that there were two separate monoclonal immunoglobulins elaborated by the lymphoma that could be associated with the glomerular injury. Although it is uncommon to make an initial diagnosis of lymphoma from a renal biopsy, it should be recognized that patients with lymphoma might develop clinically significant renal sequelae secondary to both direct and indirect mechanisms of lymphoma-mediated nephropathy.

COL1A1::PDGFB fusion-associated uterine sarcoma and response to Imatinib: A case report.

Uterine sarcomas are rare neoplasms of the uterus, some of which are associated with distinctive gene fusions. COL1A1::PDGFB fusion uterine sarcoma is a recently described entity that shares the same genetic alteration as dermatofibrosarcoma protuberans. These uterine sarcomas have a nonspecific spindle cell sarcoma appearance and are CD34 positive by immunohistochemistry. Accurate diagnosis relies on identification of the characteristic fusion by molecular genetic methods. The importance of diagnosing this entity lies in its potential response to targeted therapy with imatinib, a tyrosine kinase inhibitor successfully used in dermatofibrosarcoma protuberans, but only one prior case of COL1A1::PDGFB fusion uterine sarcoma treated with imatinib has been reported. Here, we describe a case of COL1A1::PDGFB fusion uterine sarcoma with response to imatinib after recurrence, with a brief review of this rare tumor.

Malignant struma ovarii: an analysis of 88 cases, including 27 with extraovarian spread.

Struma ovarii that display extraovarian spread or later recurrence is exceedingly rare. Among 88 patients with "malignant" struma ovarii followed for prolonged periods, several features helped to predict the adverse clinical course. Adhesions (graded 2 to 4+), peritoneal fluid (> or =1 L) or ovarian serosal rent were worrisome features, occurring in 74% of 27 biologically malignant tumors but only 10% of 61 clinically benign tumors. The size of the strumal component rather than the overall size of the ovarian teratoma also had some predictive value. Tumors with a strumal component < or =6 cm recurred rarely (7%), whereas 33% of the consult and 88% of the literature cases > or =12 cm were clinically malignant. Except for a papillary pattern or poorly differentiated cancer, no microscopic feature reliably predicted the clinical outcome, including those typically associated with malignancy in primary thyroid tumors. Among the consult cases, 7% with histologic follicular adenomas and 29% with papillary carcinomas were clinically malignant. Unequivocal vascular invasion was rare, precluding assessment of its effect. Optically clear nuclei, when extensive, were useful to diagnose papillary carcinoma, but were present nevertheless in smaller numbers in both macrofollicular and microfollicular adenomas. Eight tumors confined initially to the ovary (stage 1) recurred. Papillary carcinomas recurred earlier (average 4 y) than follicular adenomatous neoplasms (average 11 y, range: 1-29 y). Overall, the survival rate for all patients was 89% at 10 years and 84% at 25 years, indicating the need for routine long-term follow-up.

Semiquantitative assessment of cytomorphologic features can predict mutation status of thyroid nodules with indeterminate cytologic diagnosis.

Molecular diagnostics increasingly direct the management of thyroid nodules with an indeterminate cytologic diagnosis. This study was undertaken to correlate cytomorphologic features with the molecular profiles in an effort to identify features predictive of molecular aberrations. One hundred eighty-nine thyroid nodules with an indeterminate thyroid cytology diagnosis (atypia of undetermined significance, suspicious for follicular lesion, and suspicious for malignancy) with an adequate sample submitted for targeted mutation detection by polymerase chain reaction or next-generation sequencing were assessed semiquantitatively for the following cytomorphologic parameters: cellularity, Hurthle cell changes, microfollicles, nuclear elongation, nuclear grooves, nuclear enlargement, nuclear atypia, extent of atypia, and colloid. Based on this evaluation, a cumulative cytomorphologic score (CCS) and a more simplified overall atypia score (OAS) were assigned to each case. Associations among mutational status and each of the aforementioned parameters, CCS, and OAS were determined. Of the 189 nodules with indeterminate cytology, 63 (33.3%) harbored at least 1 mutation. RAS and BRAF were the most common mutations, found in 34 (18.0%) and 13 (6.9%) cases, respectively. Both CCS and OAS were highly associated with the presence of all mutations (P < .0001) and with the presence of BRAF and RAS mutations in particular (all P < .01). Semiquantitative assessment of various cytomorphologic features in indeterminate thyroid cytology cases showed a strong association of higher OAS and CCS and incidence of BRAF and RAS mutations. Using a more objective approach to thyroid cytology can potentially decrease the overall number of indeterminate diagnoses, leading to fewer repeat procedures and unnecessary surgical procedures.

Decidual granulomatous reaction in a placenta from a preeclamptic pregnancy: a case report and review of the literature.

We report a case of decidual perivascular non-necrotizing granulomas in a placenta from a pregnancy complicated by severe preeclampsia with no evidence of infection. The mother was a 20-year-old primigravida with severe preeclampsia diagnosed in the third trimester with subsequent delivery of a healthy baby boy at 37 weeks 5 days gestation. Pathologic examination of the placenta showed scattered non-necrotizing granulomas in decidua, often adjacent to remodeled decidual arteries without fibrinoid necrosis. These were well-formed, non-necrotizing granulomas with scant lymphoid cuffs. Polarization microscopy did not show foreign material. There were no histopathologic or clinical findings suggestive of maternal-fetal infection or systemic vasculitis at the time of delivery, and the mother had no other reported conditions associated with granulomatous inflammation. Our case demonstrates that granulomatous reaction may be seen in the placenta from a pregnancy complicated by severe preeclampsia, although work-up for infection may be indicated.