Digital and manual interfollicular Ki-67 are associated with a progression-free survival in patients with low-grade follicular lymphoma.

OBJECTIVES: Novel histopathologic prognostic factors are needed to identify patients with follicular lymphoma (FL) at risk of inferior outcomes. Our primary objective was to evaluate the Ki-67 proliferative index in follicular and interfollicular areas in tissue biopsy specimens from patients with newly diagnosed FL and correlate with clinical outcomes. Our secondary objective was to correlate PD-L1 and LAG-3 with clinical outcomes. METHODS: Seventy cases of low-grade FL from the University of Minnesota were evaluated with Ki-67 immunohistochemical stain. Ki-67 expression as a continuous variable was interpreted digitally and manually in follicular and interfollicular areas. Progression-free survival (PFS) and overall survival (OS) were analyzed by Cox regression, and hazard ratios (HRs) per 10-point increase in Ki-67 were calculated. RESULTS: Progression-free survival at 4 years was 28% (95% CI, 19%-41%). Interfollicular, but not follicular, Ki-67 was associated with PFS by manual (HR, 1.33; P = .01) and digital (HR, 1.38; P = .02) analysis. Digital and manual Ki-67 were only moderately correlated but demonstrated similar effects on PFS. At 4 years, OS was 90% with no association with follicular or interfollicular Ki-67 proliferation. CONCLUSIONS: Higher interfollicular Ki-67 by either digital or manual analysis is associated with a poorer PFS in patients with low-grade FL. These results suggest further validation of this marker is warranted to improve pathologic risk stratification at FL diagnosis. PD-L1 and LAG-3 were not associated with PFS or OS.

Primary angiosarcoma of the spleen, a rare indication for splenectomy: a case report.

INTRODUCTION AND IMPORTANCE: Primary angiosarcoma of the spleen is a rare condition with a nonspecific clinical presentation and is associated with a poor prognosis. We describe two patients with primary splenic angiosarcoma successfully treated with splenectomy and adjuvant chemotherapy. CASE PRESENTATIONS: Case 1: A 50-year-old female presented with fatigue and left-sided rib, shoulder, and abdominal pain. A CT scan demonstrated a large splenic mass, and biopsy was diagnostic of angiosarcoma. An open en bloc resection of the spleen was performed, and pathologic examination confirmed high-grade angiosarcoma; the surgical margins were negative. The patient received pegylated liposomal doxorubicin (PLD) and ifosfamide; she demonstrated no evidence of recurrence with four years of follow-up. Case 2: A 70-year-old male presented with acute back pain. A CT scan demonstrated a splenic mass; biopsy was diagnostic of angiosarcoma. The patient underwent open splenectomy, and pathology revealed high-grade angiosarcoma; the surgical margins were positive. The patient received PLD and ifosfamide but presented three years later with metastatic tumor to the spine. The patient had a favorable tumor response to pembrolizumab. The patient's tumor burden remains stable at 5 years following splenectomy. CLINICAL DISCUSSION: Angiosarcoma of the spleen is a rare clinical entity and is often challenging to diagnose early. Moratality is high, especially in the case of metastasis or spontaneous rupture. CONCLUSION: Due to the rare nature of this tumor, optimal treatment is not known. Here, we show excellent response in two patients to surgery combined with adjuvant therapy.

Surface Ki-67 Expression Improves Reproducibility of Dysplasia Diagnosis in Barrett's Esophagus.

OBJECTIVES: Many studies have shown poor reproducibility among pathologists for diagnosing dysplasia in Barrett's esophagus (BE). Immunohistochemical stains (IHC) are not widely used due to overlapping expression patterns in reactive and dysplastic processes. We hypothesized that markers involved in cell-cycle (cyclin D1, Ki-67, P16), differentiation/cell-cell interaction (ß-catenin, SATB2 CD44, OCT4) and senescence (γH2AX) would produce different results in reactive and dysplastic processes. METHODS: A micrograph album of 40 H&E and matching IHCs depicting optimally oriented lesions were evaluated independently by 3 pathologists. Expression was scored separately in the surface, isthmus, and base regions of the glands. RESULTS: Statistical analysis showed that surface Ki-67 expression showed the largest difference in expression and smallest P value (P < .001) for identifying dysplasia. At a cutoff level of 5% or less, negative predictive value (NPV) was 100%. κ correlation between pathologists improved from substantial to almost perfect (0.70-0.95) using ancillary surface Ki-67. CONCLUSION: A case-control study with glass slides including all diagnostic categories using this parameter confirmed improved κ correlation among pathologists (0.29 vs 0.60), better correlation with outcomes (76% vs 69%), increased odd risks (15.3) for progression in positive cases, and an improvement in sensitivity (88% vs 64%) and NPV (88% vs 73%) compared to histology alone.

Perianal Histoplasmosis Presenting as a Mass Suspicious for Malignancy: A Case Report with Review of Gastrointestinal Manifestations of Histoplasmosis.

BACKGROUND Disseminated histoplasmosis, a disease that can present years after exposure to the causative organism, may manifest in many diverse ways. Although the gastrointestinal tract is involved in most cases, the initial presentation occurring along the gastrointestinal tract, including the colon and rectum, is infrequent. CASE REPORT This case report describes a 66-year-old male patient who presented with an indurated painful perianal lesion that appeared highly suspicious for malignancy on imaging. The patient had no known history of well-established immunocompromised state except for a short course of prednisolone for chronic obstructive pulmonary disease management. A biopsy of the mass was performed, showing chronic inflammation with clusters of epithelioid histiocytes containing characteristic, PAS-fungus stain-positive, intracellular yeast forms consistent with histoplasmosis. There was no evidence of malignancy. A subsequent work-up revealed perihilar nodularity on chest X-ray suggestive of calcified granuloma, a positive Histoplasma Capsulatum Antigen test result, and mildly decreased CD4: CD8 ratio of unknown significance. HIV testing was negative. Treatment with itraconazole and terbinafine was initiated, and at 5-months follow-up, the patient reported significant improvement in signs and symptoms, with undetectable Histoplasma antigen on repeat testing. CONCLUSIONS This case represents an extremely rare presentation of histoplasmosis infection, and highlights the fact that presenting symptoms of histoplasmosis can be vague and may mimic other disease processes, including neoplasia. Biopsy of the lesion with PAS staining and serologic testing is critical in establishing the correct diagnosis.

Pseudomyogenic hemangioendothelioma-A case report and review of the literature.

Pseudomyogenic hemangioendothelioma (PMH) of bone is a very rare tumor and frequently presents at multiple locations. PMH is difficult to diagnose by imaging and histopathologic features. Various and partially discordant imaging findings have been reported in case reports and small case series. We report a case of a 63-year-old man with PMH isolated to the sacrum, presenting with chronic intermittent buttock pain that was incidentally identified on imaging for acute pancreatitis. We believe that learning about PMH of bone will help to include this disease in the differential diagnosis of lytic lesions of the sacrum. Becoming aware of the various and sometimes discordant imaging findings of this rare entity is important and helpful for radiologists, pathologists, and orthopedic surgeons.