Breast implant-associated anaplastic large cell lymphoma: clinical follow-up and analysis of sequential pathologic specimens of untreated patients shows persistent or progressive disease.

Breast implant-associated anaplastic large cell lymphoma (ALCL) is a distinctive type of T-cell lymphoma that arises around textured-surface breast implants. In a subset of patients, this disease can involve surrounding tissues, spread to regional lymph nodes, and rarely metastasize to distant sites. The aim of this study was to assess sequential pathologic specimens from patients with breast implant-associated ALCL to better understand the natural history of early-stage disease. To achieve this goal, we searched our files for patients who had breast implant-associated ALCL and who had undergone earlier surgical intervention with assessment of biopsy or cytologic specimens. We then focused on the patient subset in whom a definitive diagnosis was not established, and patients did not receive current standard-of-care therapy at that time. We identified a study group of ten patients with breast implant-associated ALCL in whom pathologic specimens were collected 0.5 to 4 years before a definitive diagnosis was established. A comparison of these serial biopsy specimens showed persistent disease without change in pathologic stage in three patients, progression in five patients, and persistence versus progression in two patients. Eventually, six patients underwent implant removal with complete capsulectomy and four underwent partial capsulectomy. Seven patients also received chemotherapy because of invasive disease, three of whom also received radiation therapy, two brentuximab vedotin after chemotherapy failure, and one allogeneic stem cell transplant. Eight patients achieved complete remission and two had partial remission after definitive therapy. At time of last follow-up, six patients were alive without disease, one had evidence of disease, one died of disease, and two patients died of unrelated cancers. In summary, this analysis of sequential specimens from patients with breast implant-associated ALCL suggests these neoplasms persist or progress over time if not treated with standard-of-care therapy.

Novel Case Report: A Previously Reported, but Pathophysiologically Unexplained, Association Between Collagenous Colitis and Protein-Losing Enteropathy May Be Explained by an Undetected Link with Collagenous Duodenitis.

Collagenous colitis (CC) is associated with non-bloody, watery diarrhea, which is pathophysiologically reasonable because normal colonic absorption (or excretion) of water and electrolytes can be blocked by the abnormally thick collagen layer in CC. However, CC has also been associated with six previous cases of protein-losing enteropathy (PLE), with no pathophysiologic explanation. The colon does not normally absorb (or excrete) amino acids/proteins, which is primarily the function of the small bowel. Collagenous duodenitis (CD) has not been associated with PLE. This work reports a novel case of CD (and CC) associated with PLE; a pathophysiologically reasonable mechanism for CD causing PLE (by the thick collagen layer of CD blocking normal intestinal amino acid absorption); and a novel association of PLE with severe COVID-19 infection (attributed to relative immunosuppression from hypoproteinemia, hypoalbuminemia, hypogammaglobulinemia, and malnutrition from PLE).

A proposal for pathologic processing of breast implant capsules in patients with suspected breast implant anaplastic large cell lymphoma.

Breast implant anaplastic large cell lymphoma is an entity recently recognized by the World Health Organization. The tumor arises around textured-surface breast implants and is usually confined to the surrounding fibrous capsule. Currently, there are no recommendations for handling and sampling of capsules from patients with suspected breast implant anaplastic large cell lymphoma without a grossly identifiable tumor. We analyzed complete capsulectomies without distinct gross lesions from patients with breast implant anaplastic large cell lymphoma. The gross appearance of the capsules as well as the presence, extent and depth of tumor cells on the luminal side and number of sections involved by lymphoma were determined by review of routine stains and CD30 immunohistochemistry. We then used a mathematical model that included the extent of tumor cells and number of positive sections to calculate the minimum number of sections required to identify 95% of randomly distributed lesions. We identified 50 patients with breast implant anaplastic large cell lymphoma who had complete capsulectomies. The implants were textured in all 32 (100%) cases with available information. Anaplastic large cell lymphoma was found in 44/50 (88%) capsules; no tumor was found in six (12%) patients who had lymphoma cells only in the effusion. The median number of sections reviewed was 20 (range, 2-240), the median percentage of sections involved by tumor was 6% (range, 0-90%), and the median percentage of sections involved by lymphoma was 10% (range, 0-90%). Invasion deep into or through the capsule was identified in 18/50 (36%) patients. In patients with breast implant anaplastic large cell lymphoma without a grossly identifiable tumor we identified a spectrum of involvement and we propose a protocol for handling, sampling and reporting these cases. The number of sections to exclude the presence of lymphoma with more than 95% certainty was supported by a mathematic rationale.

Fatal central nervous system co-infection with SARS-CoV-2 and tuberculosis in a healthy child.

BACKGROUND: Central and peripheral nervous system symptoms and complications are being increasingly recognized among individuals with pandemic SARS-CoV-2 infections, but actual detection of the virus or its RNA in the central nervous system has rarely been sought or demonstrated. Severe or fatal illnesses are attributed to SARS-CoV-2, generally without attempting to evaluate for alternative causes or co-pathogens. CASE PRESENTATION: A five-year-old girl with fever and headache was diagnosed with acute SARS-CoV-2-associated meningoencephalitis based on the detection of its RNA on a nasopharyngeal swab, cerebrospinal fluid analysis, and magnetic resonance imaging findings. Serial serologic tests for SARS-CoV-2 IgG and IgA showed seroconversion, consistent with an acute infection. Mental status and brain imaging findings gradually worsened despite antiviral therapy and intravenous dexamethasone. Decompressive suboccipital craniectomy for brain herniation with cerebellar biopsy on day 30 of illness, shortly before death, revealed SARS-CoV-2 RNA in cerebellar tissue using the Centers for Disease Control and Prevention 2019-nCoV Real-Time Reverse Transcriptase-PCR Diagnostic Panel. On histopathology, necrotizing granulomas with numerous acid-fast bacilli were visualized, and Mycobacterium tuberculosis complex DNA was detected by PCR. Ventricular cerebrospinal fluid that day was negative for mycobacterial DNA. Tracheal aspirate samples for mycobacterial DNA and culture from days 22 and 27 of illness were negative by PCR but grew Mycobacterium tuberculosis after 8 weeks, long after the child's passing. She had no known exposures to tuberculosis and no chest radiographic findings to suggest it. All 6 family members had normal chest radiographs and negative interferon-γ release assay results. The source of her tuberculous infection was not identified, and further investigations by the local health department were not possible because of the State of Michigan-mandated lockdown for control of SARS-CoV-2 spread. CONCLUSION: The detection of SARS-CoV-2 RNA in cerebellar tissue and the demonstration of seroconversion in IgG and IgA assays was consistent with acute SARS-CoV-2 infection of the central nervous infection. However, the cause of death was brain herniation from her rapidly progressive central nervous system tuberculosis. SARS-CoV-2 may mask or worsen occult tuberculous infection with severe or fatal consequences.

A 14-Year Study of 398 Esophageal Adenocarcinomas Diagnosed Among 156,256 EGDs Performed at Two Large Hospitals: An Inlet Patch Is Proposed as a Significant Risk Factor for Proximal Esophageal Adenocarcinoma.

BACKGROUND: An association between inlet patches and proximal esophageal adenocarcinomas is currently suspected because of numerous case reports of simultaneous occurrence of both diseases. AIMS: To analyze whether inlet patches are significantly associated with proximal esophageal adenocarcinomas in a large population. METHODS: Computerized search of pathology and EGD reports revealed 398 cases of esophageal adenocarcinomas among 156,236 EGDs (performed on 106,510 patients) diagnosed by histopathology performed at Royal Oak/Troy, William Beaumont Hospitals, 2003-2016. Adenocarcinomas localized as distal, middle, or proximal; and characterized as associated versus unassociated with inlet patches. Medical records were reviewed. Endoscopic photographs, radiologic images, and pathologic slides were re-reviewed. Two researchers independently performed systematic computerized literature searches; cases of simultaneous diseases identified by consensus. RESULTS: Adenocarcinoma locations included: distal-381, middle-14, and proximal esophagus-3. Five patients had inlet patches with esophageal adenocarcinomas located at: distal-2, middle-0, and proximal esophagus-3 (relative frequency of inlet patches with cancers of distal/middle esophagus = 2/395 [.5%] vs. proximal esophagus = 3/3 [100%], p < .000001, 95% OR CI > 50.1, Fisher's exact test). Cases of proximal esophageal adenocarcinomas within inlet patches included: (1) Seventy-eight-year-old man presented with dysphagia. Neck CT showed proximal esophageal mass. EGD revealed semi-circumferential, multinodular, 3.0 × 1.5 cm mass within inlet patch. Histopathology of biopsies revealed moderately-to-poorly differentiated adenocarcinoma. Patient received chemoradiotherapy and expired 2 years later. (2) Seventy-nine-year-old man presented with anorexia and weight loss. EGD demonstrated proximal esophageal mass within inlet patch. Histopathology of biopsies revealed poorly differentiated, signet ring cell adenocarcinoma. Chest CT revealed 3.4 × 2.1-cm-proximal esophageal mass. Patient expired 4 months later. (3) Sixty-year-old man presented with dysphagia. EGD revealed 4-cm-long, semi-circumferential, proximal esophageal mass within inlet patch. Histopathology of biopsies revealed poorly differentiated adenocarcinoma. Patient underwent emergency esophagectomy for esophageal perforation 2 weeks after initiating chemoradiotherapy, and died shortly thereafter. Literature review revealed 39 cases of simultaneous disease. STUDY LIMITATIONS: Potential underreporting by endoscopists of inlet patches at EGD. CONCLUSIONS: Study supplements 39 previously reported cases of simultaneous disease, by adding three new cases, and by novel report of statistically significant association between these two entities, which has important implications in the pathophysiology of proximal esophageal adenocarcinoma.

A Statistically Significant Association Between Esophageal Granular Cell Tumors and Eosinophilic Esophagitis: A 16-year Analysis at Two Large Hospitals of 167,434 EGDs.

BACKGROUND: Esophageal granular cell tumor (eGCT) is a rare, usually benign, neoplasm of neuroectodermic origin. Eosinophilic esophagitis (EoE) is a relatively uncommon, immune-mediated, chronic disease. Both diseases commonly present with dysphagia. One case has been reported of simultaneous occurrence of both diseases. AIMS: To determine the association between diseases. METHODS: The present study was an IRB-approved, retrospective review of esophagogastroduodenoscopies (EGDs) with esophageal biopsies from two large hospitals, 1999-2014. RESULTS: Among 29,235 EGDs with esophageal biopsies for 16 years (167,434 total EGDs), 16 patients had pathologically diagnosed eGCT, and 1225 patients had pathologically diagnosed EoE. Five (31%) of 16 patients with eGCT had concomitant EoE (p = 0.001, OR 10.43, 95% ORCI 3.16-32.44, Fisher's exact test). Patients with simultaneous eGCT and EoE were young (mean age = 33.6 ± 12.9 years). Three were female. Dysphagia was presenting symptom in 4 (80%) of patients. Three had asthma. All five patients had > 20 eosinophils/hpf in esophageal biopsy specimens. Three patients had endoscopic esophageal abnormalities suggesting EoE. Four patients were treated with a PPI (before and after diagnosis of EoE), and 2 patients underwent six-food-elimination diet with partial symptomatic improvement. The eGCTs averaged 13.4 ± 4.2 mm in maximal diameter and were located in upper-2, middle-2, and lower esophagus-2 (1 patient had 2 eGCTs). eGCTs were endoscopically resected-3 patients, and monitored-2 patients. Surveillance endoscopies revealed no recurrence or growth of eGCTs after resection (mean follow-up = 4.6 years). CONCLUSIONS: This novel report of 5 patients with simultaneous EoE and eGCT adds to one, previously published case and suggests these two diseases are associated, and have a common pathophysiologic link, despite apparently different pathogenesis. Large, prospective, endoscopic and pathologic studies are warranted to further investigate this association.

Chromogranin A staining as a prognostic variable in newly diagnosed Gleason score 7-10 prostate cancer treated with definitive radiotherapy.

PURPOSE: To demonstrate the association of neuroendocrine differentiation, as identified by chromogranin A (CgA) staining, with clinical outcomes in newly diagnosed prostatic adenocarcinoma treated with definitive radiotherapy (RT). MATERIALS/METHODS: Patients with Gleason score ≥7 adenocarcinoma were identified from our outcomes database. RT consisted of external beam, brachytherapy, or external beam with brachytherapy boost. Biopsy specimens were stained for neuroendocrine differentiation with CgA. Results were interpreted by a single pathologist. CgA staining was quantified as 0%, <1%, 1-10%, or >10% of tumor cells. Clinical outcomes were blinded at the time of pathologic evaluation. RESULTS: CgA staining was performed on 289 patients. 149 patients had Gleason score 7, and 140 were Gleason score 8-10. Median follow-up was 6.5 years. For patients with <1% versus >1% CgA staining, pretreatment characteristics were well-balanced. CgA staining was detected in 90 cases (31%). 58 patients had focal positive (<1%) CgA staining, and 32 cases had >1% of tumor cells CgA positive. Patients with >1% CgA staining had inferior biochemical control, clinical failure, distant metastases (DM), and cause-specific survival (CSS) rates. Ten-year rates of DM were 8% versus 48% for patients with <1% versus >1% CgA positive cells, respectively (P < 0.001). CSS at 10 years was 95% versus 76%, respectively (P < 0.001). Local control was equivalent in the two patient cohorts. Patients with <1% CgA staining had similar outcomes to those patients with 0% staining. CONCLUSIONS: Neuroendocrine differentiation involving >1% of tumor cells on prostate cancer biopsies is a predictor of DM and CSS in patients treated with primary RT.

Clinical presentation and comparison of surgical outcome for segmental resection vs. Whipple's procedure for solid pseudopapillary tumor: Report of six new cases & literature review of 321 cases.

AIM: Report 6 new cases of solid-pseudopapillary-pancreatic-tumor, comprehensively review 321 cases reported in American literature, and compare outcomes for segmental resection vs.. Whipple's procedure. METHODS: Cases of solid-pseudopapillary-tumor at William Beaumont Hospital, 1999-2011, identified by computerized analysis of pathology reports. Comprehensive review of all American cases identified by computerized literature review. Segmental resection includes open/laparoscopic central pancreatectomy and anatomic distal pancreatectomy, but excludes enucleation. RESULTS: Six cases of solid-pseudopapillary-pancreatic-tumors (0.5% of all solid pancreatic lesions), occurred during 1999-2011 at the hospital. Mean age at diagnosis = 27.7 years. All 6 were female. All patients had abdominal pain. Mean symptom duration = 10.0 days. All patients had normal routine blood tests. Mean APACHE II score at diagnosis = 1.8. All six patients had single heterogeneous lesions, with cystic/solid components. All patients underwent surgery: segmental resection-4, Whipple's procedure-2. Tumors were uniformly diagnosed by surgically resected tissue. Mean tumor size = 5.7 cm. Mean postoperative length of stay = 4.0 days for segmental resection (N = 4) vs. 14.0 days for Whipple's procedure (N = 2). All 6 patients are alive and well to-date, without evident local recurrence or metastasis. In a literature review, 45 patients undergoing Whipple's procedure versus 34 patients undergoing segmental resection, had significantly longer mean postoperative hospitalization (16.4 vs. 4.3 days, p = 0.01), and had increased unadjusted mortality (20.2% vs. 2.2%, p = 0.018). However, this mortality difference became insignificant when adjusting for longer mean follow-up of Whipple's procedure patients (Kaplan-Meier-survival-curve, p = 0.75). CONCLUSIONS: This work suggests segmental resection of these pancreatic tumors localized to the body/tail may have a better surgical outcome than Whipple's procedure for tumors localized to the pancreatic head. Further studies are necessary.

Characterization of the syndrome of acute liver failure caused by metastases from breast carcinoma.

AIM: To characterize syndrome of acute liver failure (ALF) from metastatic breast cancer to promote premortem diagnosis. Up to now, only 25 % of the reported 32 cases of this syndrome were diagnosed premortem. METHODS: Cases identified by computerized literature review and review of files maintained by senior investigator. RESULTS: Among 32 cases, average age at presentation was 47.9 ± 9.9 years. Common signs include jaundice, hepatomegaly, shifting dullness, and bilateral leg edema. Mean serum level of AST was 296.4 ± 204.0 U/L, ALT, 183.2 ± 198.9 U/L; alkaline phosphatase, 641.5 ± 610.1; and total bilirubin, 8.6 ± 8.3 mg/dL. Twenty-seven patients (84 %) have known prior breast cancer (mean diagnosis = 4.1 + 4.8 years earlier). Abdominal ultrasound findings (N = 10) include hepatomegaly in three cases, heterogeneous/multifocal hepatic lesions in three, ascites in three, and other in two. Abdominal CT findings (N = 16) include heterogeneous/multifocal hepatic lesions in six cases, ascites in five, hepatomegaly in three, cirrhosis in three, fatty liver in two, other in two. Hepatic metastases may not be suspected when abdominal CT shows no hepatic lesions. The diagnosis is made postmortem in 24 cases and antemortem in eight, with a statistically significant trend of increasing premortem diagnosis since 2000 (0 % before 2000 vs. 50 % after 2000; p = .001, 95 %--ORCI ≥ 2.86, Fisher's exact test). A new case of ALF from breast cancer is reported with notable features: abdominal CT revealed no discrete hepatic lesions despite widespread hepatic metastases demonstrated by liver biopsy; hepatic metastases occurred 21 years after original breast primary; and original diagnosis of lobular breast cancer in primary lesion was corrected to mixed ductal and lobular carcinoma, based on immunohistochemistry, performed 21 years afterward. CONCLUSIONS: This review characterizes the clinical presentation and natural history of this syndrome to promote liver biopsy for premortem diagnosis and appropriate therapy.

Neuroendocrine carcinoma of the urinary bladder: a retrospective study of CT findings.

PURPOSE: The purpose of this study was to evaluate the radiographic features of neuroendocrine carcinoma of the urinary bladder (NECB) on CT and to review the literature regarding carcinogenesis, treatment, and prognosis. METHODS: The presenting CT of patients with pathology-proven NECB were retrospectively reviewed for features including size and appearance of the bladder mass, the presence of hydronephrosis, bladder wall thickening, invasion of perivesical fat, lymph nodes, and distant metastasis. Follow-up imaging and the medical record were reviewed to determine patient treatment and overall survival. RESULTS: Sixteen patients (13 males, 3 females) were diagnosed with NECB with a mean age of 75.5 years (range 48-90). The characteristic CT appearance was a large polypoid bladder mass (average size 4.9 cm). Extension into the perivesical fat, adjacent organ involvement, and distant metastases were common. CONCLUSION: NECB is an aggressive primary neoplasm of the bladder that presents on CT as a large bladder mass with local extension into the perivesical fat, involvement of adjacent organs, and metastasis.

Segmental testicular infarction: sonographic findings and pathologic correlation.

Segmental testicular infarction can mimic testicular carcinoma on sonography and can lead to unnecessary orchiectomy. This case series describes and correlates sonographic and histologic findings of 7 pathologically proven segmental testicular infarction cases. Segmental testicular infarction should be suspected on sonography when a geographic lesion with low or mixed echogenicity has absent or near-absent flow in a patient with scrotal pain. A hyperechoic rim and peripheral hyperemia correspond to interstitial hemorrhage and inflammatory changes. As an infarct evolves, it becomes more discrete and hypoechoic as ghost outlines replace seminiferous tubules. Follow-up or contrast-enhanced magnetic resonance imaging or sonography can increase diagnostic confidence in suspected cases and prevent unnecessary orchiectomy.

Type-specific human papillomavirus DNA detected in atypical glandular cell Pap tests.

OBJECTIVES: To evaluate the presence of type-specific human papillomavirus (HPV) DNA in atypical glandular cells (AGCs) from cervical liquid-based cytology and to report the relationship between HPV types and cervical histological abnormalities. STUDY DESIGN: We used a nested multiplex polymerase chain reaction assay to test AGC Papanicolaou (Pap) tests for the presence of 14 high-risk (HR) HPV types. RESULTS: HR HPV types were detected in 33 of 161 AGC Pap tests (20.3%). Types 16 and/or 18 were detected in 13 samples (8%). Eight other HPV types were detected in 1-4 samples each. HPV-associated disease was diagnosed in 8 AGC cases (8%) with available histology results. The sensitivity and specificity of the HR HPV test were 87.5 and 90%, respectively, and the negative predictive value (NPV) was 99%. For a test that can isolate HPV types 16 and 18, the sensitivity and specificity were 62.5 and 100%, respectively, the positive predictive value (PPV) was 100% and the NPV was 97%. CONCLUSION: HPV 16 and 18 were the most common types detected in AGC Paps. We found high specificity, PPV and NPV with a test that can isolate these 2 HPV types. These results indicate a possible role for type-specific HPV testing in the management of AGC Pap tests.

Simultaneous Massive Esophageal Mucosal Candidiasis and Profound Cytomegaloviral Esophageal Ulcers with Recurrence of Both Infections 12 Years Later in a Patient with Long-Standing AIDS: Endoscopic, Radiologic, and Pathologic Findings.

Immunocompromised patients with acquired immunodeficiency syndrome (AIDS) can develop opportunistic esophageal candidial and cytomegaloviral infections. A case is reported which extends the clinico-endoscopic severity of these infections. A 32-year-old bisexual man with AIDS since 1997, and intermittently compliant with antiretroviral therapy, presented (2007) with dysphagia and 32 kg-weight loss. EGD revealed a massive, cheesy, esophageal mucosal exudate from Candida albicans. Cytomegalovirus was isolated by viral culture. The patient improved after fluconazole/ganciclovir therapy. The patient re-presented (2019) with hematemesis and dysphagia. EGD revealed cheesy esophageal exudate and profound "punched out" esophageal ulcers mimicking pseudo-diverticula. Histopathology confirmed candidiasis. Viral cultures revealed cytomegalovirus. Barium esophagram revealed deep esophageal ulcers/pseudo-diverticula. Repeat EGD 8 weeks later after ganciclovir/micafungin therapy revealed mostly healed lesions. This demonstrates that AIDS patients may have massive mucosal esophageal candidiasis; that both infections can recur years after apparent eradication; and that cytomegaloviral esophageal ulcers may be profound and mimic pseudo-diverticula. A comprehensive literature review revealed only one abstract of esophageal pseudo-diverticula associated with cytomegalovirus. Simultaneous esophageal candidial and CMV infections have also been rarely reported in immunocompromised patients without AIDS.

Investigation of the Prognostic Significance of Neuroendocrine Differentiation in Gleason Score 7 to 10 Prostate Adenocarcinoma in Patients With Distant Metastasis After Definitive Radiotherapy.

OBJECTIVES: We investigated the prognostic implications of neuroendocrine differentiation (NED) in prostate adenocarcinoma detected by chromogranin A (CgA) in patients who developed distant metastasis (DM) after radiotherapy. METHODS: Patients with Gleason score 7 to 10 conventional acinar prostate adenocarcinoma treated with definitive radiotherapy and with core biopsy CgA staining completed were reviewed. Patients who developed DM, defined as disease beyond the primary tumor or pelvic lymph nodes, underwent detailed chart review. Statistical analysis included Kaplan-Meier estimates and descriptive statistics to compare based on quantification of CgA staining. RESULTS: Thirty-five patients had confirmed DM. Twenty-five patients had less than 1% of cells staining positive for CgA, and 10 patients had more than 1%. Median overall survival (OS) time was 3.26 and 1.04 years, respectively (P = .52). Median cause-specific survival (CSS) was 6.15 and 1.04 years, respectively (P = .21). Fifty-six percent of patients with CgA less than 1% died of prostate cancer compared with 90% of those with CgA more than 1% (P = .059). There were no significant differences in sites of metastatic disease or administration of systemic therapies. CONCLUSIONS: No significant differences in OS and CSS were observed based on NED detected by CgA. Reduced median survival time and increased cancer-related death in cases with focal NED generates the hypothesis of inferior outcomes among patients with documented DM.

Pancreatic Ganglioneuroma Presenting in an Octogenarian.

Pancreatic ganglioneuromas occur mostly in children and rarely in young adults, with no cases reported in adults older than 60 years. An 86-year-old-woman, with active advanced multiple myeloma, presented with epigastric pain for 2 days. Abdominal and pelvic computed tomography demonstrated a distended gallbladder, mildly dilated biliary tree, and a 13 × 8-mm hypodense mass in pancreatic body, without extrapancreatic invasion at endoscopic ultrasound. Fine-needle endoscopic ultrasound-guided core biopsy revealed characteristic histopathology of ganglioneuroma, as confirmed by immunohistochemical positivity for S100, SOX-10, and synaptophysin. This demonstrates novel finding of pancreatic ganglioneuroma occurring in the elderly. Lesion inclusion in the differential diagnosis may mandate tissue for pathologic diagnosis and complete lesion resection.