A case-control autopsy series of liver pathology associated with novel coronavirus disease (COVID-19).

BACKGROUND: Although severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) responsible for coronavirus disease 2019 (COVID-19) is most well-known for causing pulmonary injury, a significant proportion of patients experience hepatic dysfunction. The mechanism by which SARS-CoV2 causes liver injury is not fully understood. The goal of this study was to describe the hepatic pathology in a large cohort of deceased patients with COVID-19 as compared to a control group of deceased patients without COVID-19. METHODS: Consented autopsy cases at two institutions were searched for documentation of COVID-19 as a contributing cause of death. A group of consecutive consented autopsy cases during the same period, negative for SARS-CoV-2 infection, was used as a control group. The autopsy report and electronic medical records were reviewed for relevant clinicopathologic information. H&E-stained liver sections from both groups were examined for pertinent histologic features. Select cases underwent immunohistochemical staining for CD 68 and ACE2 and droplet digital polymerase chain reaction (ddPCR) assay for evaluation of SARS-CoV2 RNA. RESULTS: 48 COVID-19 positive patients (median age 73, M:F 3:1) and 40 COVID-19 negative control patients (median age 67.5, M:F 1.4:1) were included in the study. The COVID-19 positive group was significantly older and had a lower rate of alcoholism and malignancy, but there was no difference in other comorbidities. The COVID-19 positive group was more likely to have received steroids (75.6 % vs. 36.1 %, p < 0.001). Hepatic vascular changes were seen in a minority (10.6 %) of COVID-19 positive cases. When all patients were included, there were no significant histopathologic differences between groups, but when patients with chronic alcoholism were excluded, the COVID-19 positive group was significantly more likely to have steatosis (80.9 % vs. 50.0 %, p = 0.004) and lobular inflammation (45.7 % vs. 20.7 %, p = 0.03). Testing for viral RNA by ddPCR identified 2 of the 18 (11.1 %) COVID-19 positive cases to have SARS-CoV-2 RNA detected within the liver FFPE tissue. CONCLUSIONS: The most significant findings in the liver of COVID-19 positive patients were mild lobular inflammation and steatosis. The high rate of steroid therapy in this population may be a possible source of steatosis. Hepatic vascular alterations were only identified in a minority of patients and did not appear to play a predominant role in COVID-19 mediated hepatic injury. Low incidence of SARS-CoV-2 RNA positivity in liver tissue in our cohort suggests hepatic injury in the setting of COVID-19 may be secondary in nature.

Digital Hepatic Iron Content: An Artificial Intelligence Model for Spatially Resolved Histologic Iron Quantitative Analysis in Liver Samples.

Currently, the precise evaluation of tissue hepatic iron content (HIC) requires laboratory testing using tissue-destructive methods based on colorimetry or spectrophotometry. To maximize the use of routine histologic stains in this context, we developed an artificial intelligence (AI) model for the recognition and spatially resolved measurement of iron in liver samples. Our AI model was developed using a cloud-based, supervised deep learning platform (Aiforia Technologies). Using digitized Pearl Prussian blue iron stain whole slide images representing the full spectrum of changes seen in hepatic iron overload, our training set consisted of 59 cases, and our validation set consisted of 19 cases. The study group consisted of 98 liver samples from 5 different laboratories, for which tissue quantitative analysis using inductively coupled plasma mass spectrometry was available, collected between 2012 and 2022. The correlation between the AI model % iron area and HIC was Rs = 0.93 for needle core biopsy samples (n = 73) and Rs = 0.86 for all samples (n = 98). The digital hepatic iron index (HII) was highly correlated with HII > 1 (area under the curve [AUC] = 0.93) and HII > 1.9 (AUC = 0.94). The percentage area of iron within hepatocytes (vs Kupffer cells and portal tract iron) identified patients with any hereditary hemochromatosis-related mutations (either homozygous or heterozygous) (AUC = 0.65, P = .01) with at least similar accuracy than HIC, HII, and any histologic iron score. The correlation between the Deugnier and Turlin score and the AI model % iron area for all patients was Rs = 0.87 for total score, Rs = 0.82 for hepatocyte iron score, and Rs = 0.84 for Kupffer cell iron score. Iron quantitative analysis using our AI model was highly correlated with both detailed histologic scoring systems and tissue quantitative analysis using inductively coupled plasma mass spectrometry and offers advantages (related to the spatial resolution of iron analysis and the nontissue-destructive nature of the test) over standard quantitative methods.

Performance of an Artificial Intelligence Model for Recognition and Quantitation of Histologic Features of Eosinophilic Esophagitis on Biopsy Samples.

We have developed an artificial intelligence (AI)-based digital pathology model for the evaluation of histologic features related to eosinophilic esophagitis (EoE). In this study, we evaluated the performance of our AI model in a cohort of pediatric and adult patients for histologic features included in the Eosinophilic Esophagitis Histologic Scoring System (EoEHSS). We collected a total of 203 esophageal biopsy samples from patients with mucosal eosinophilia of any degree (91 adult and 112 pediatric patients) and 10 normal controls from a prospectively maintained database. All cases were assessed by a specialized gastrointestinal (GI) pathologist for features in the EoEHSS at the time of original diagnosis and rescored by a central GI pathologist (R.K.M.). We subsequently analyzed whole-slide image digital slides using a supervised AI model operating in a cloud-based, deep learning AI platform (Aiforia Technologies) for peak eosinophil count (PEC) and several histopathologic features in the EoEHSS. The correlation and interobserver agreement between the AI model and pathologists (Pearson correlation coefficient [rs] = 0.89 and intraclass correlation coefficient [ICC] = 0.87 vs original pathologist; rs = 0.91 and ICC = 0.83 vs central pathologist) were similar to the correlation and interobserver agreement between pathologists for PEC (rs = 0.88 and ICC = 0.91) and broadly similar to those for most other histologic features in the EoEHSS. The AI model also accurately identified PEC of >15 eosinophils/high-power field by the original pathologist (area under the curve [AUC] = 0.98) and central pathologist (AUC = 0.98) and had similar AUCs for the presence of EoE-related endoscopic features to pathologists' assessment. Average eosinophils per epithelial unit area had similar performance compared to AI high-power field-based analysis. Our newly developed AI model can accurately identify, quantify, and score several of the main histopathologic features in the EoE spectrum, with agreement regarding EoEHSS scoring which was similar to that seen among GI pathologists.

Artificial intelligence-based reticulin proportionate area - a novel histological outcome predictor in hepatocellular carcinoma.

AIMS: Reticulin stain is used routinely in the histological evaluation of hepatocellular carcinoma (HCC). The goal of this study was to assess whether the histological reticulin proportionate area (RPA) in HCCs predicts tumour-related outcomes. METHODS AND RESULTS: We developed and validated a supervised artificial intelligence (AI) model that utilises a cloud-based, deep-learning AI platform (Aiforia Technologies, Helsinki, Finland) to specifically recognise and quantify the reticulin framework in normal livers and HCCs using routine reticulin staining. We applied this reticulin AI model to a cohort of consecutive HCC cases from patients undergoing curative resection between 2005 and 2015. A total of 101 HCC resections were included (median age = 68 years, 64 males, median follow-up time = 49.9 months). AI model RPA reduction of > 50% (compared to normal liver tissue) was predictive of metastasis [hazard ratio (HR) = 3.76, P = 0.004, disease-free survival (DFS, HR = 2.48, P < 0.001) and overall survival (OS), HR = 2.80, P = 0.001]. In a Cox regression model, which included clinical and pathological variables, RPA decrease was an independent predictor of DFS and OS and the only independent predictor of metastasis. Similar results were found in the moderately differentiated HCC subgroup (WHO grade 2), in which reticulin quantitative analysis was an independent predictor of metastasis, DFS and OS. CONCLUSION: Our data indicate that decreased RPA is a strong predictor of various HCC-related outcomes, including within the moderately differentiated subgroup. Reticulin, therefore, may represent a novel and important prognostic HCC marker, to be further explored and validated.

Invasive urothelial carcinoma with squamous differentiation and associated high-risk human papilloma virus infection: Clinical, cytologic, and histologic features of a rare entity.

We correlate the fine needle aspiration (FNA) cytologic findings with the histologic features of an invasive high-grade urothelial carcinoma showing squamous differentiation in the setting of high-risk Human Papilloma Virus (hrHPV) infection. To our knowledge, only extensive urinary bladder catheterization has been associated with hrHPV-positive urothelial carcinoma with squamous differentiation, and rarely at that. Herein, we present a case arising in a patient with only sparse and intermittent catheterization. A 69-year-old woman presented with voiding difficulties, and after continued symptoms, a Foley catheter was placed, and a cystoscopy procedure revealed two 1-2 cm inflammatory masses. Excisional biopsies were interpreted as papillary urothelial carcinoma. One month follow-up pelvic imaging demonstrated a new mass involving the urinary bladder neck, with irregular wall thickening and perivesical fat stranding, as well as probable vaginal involvement. CT-guided FNA (CT-FNA) to collect smears and core biopsies revealed an invasive urothelial carcinoma with squamous differentiation. HPV-cytopathic changes amid squamous metaplasia and dysplasia were noted on FNA smears with HPV E6/E7 RNA in situ hybridization (ISH) showing on the FNA core biopsy specimen. Immunostains showed that the tumor cells were positive for P16 (strong, diffuse), CK7, p63, ER, and GATA3 (patchy). Subsequent radical cystectomy revealed the extent of the patient's carcinoma, with direct extension to the vaginal wall, and involvement of the radial soft tissue resection margins. Describing the cytomorphologic features of a hrHPV positive urothelial carcinoma with squamous differentiation, without an extensive history of urinary catheterization or prior known history of HPV infection, emphasizes the role of cytopathology as a powerful diagnostic tool for recognizing a unique and unexpected lesion.

Multi-institutional development and validation of a novel histologic grading system for colonic graft-versus-host disease.

Graft-versus-host disease (GVHD) remains a major complication for patients who have undergone hematopoietic stem cell transplantation. The Lerner system is the most widely used histologic grading score for gastrointestinal GVHD but its clinic utility is debated. The aim of our study was to develop a novel histologic grading system for gastrointestinal GVHD that incorporates independent evaluation of both apoptotic counts and crypt destruction. Colonic biopsies taken to assess for GVHD were retrospectively assessed for: Crypt damage (No crypt dropout or ulceration-0; crypt dropout without ulceration-1; ulceration-2) and crypt apoptotic counts (No apoptosis-0; 1-6 apoptotic bodies per 10 contiguous crypts-1; >6apoptotic bodies per 10 contiguous crypts-2). The two scores were added together to get an overall grade (0-4). Alternative apoptotic cutoff points were examined. An apoptotic cutoff of >9 apoptotic bodies per 10 contiguous crypts marginally improved the area under the curve (AUC), but the AUCs from the resulting novel grade calculations were not significantly different (p = 0.10). Lerner grading was also applied. The study group consisted of an initial analysis cohort (n = 191) and a second validation cohort from a separate institution (n = 97). In the initial analysis cohort, our histologic grading system provided prognostic stratification for GVHD-related death within 6 months (p = 0.0004, AUC = 0.705). The Lerner system performed similarly in terms of providing prognostic stratification for GVHD-related death (p = 0.0001, AUC = 0.707). In the external validation cohort, our histologic grading system was not associated with GVHD-related death (p = 0.14, AUC = 0.621), but the Lerner system was associated with GVHD-related death (p = 0.048, AUC = 0.663). While our grading system may have some advantages compared to the Lerner system, due to lack of reproducibility we do not currently recommend widespread adoption of this system. Nonetheless, we present a standardized tool for assessing both apoptosis and crypt damage. Future studies assessing alternative histologic grading systems with external validation and further examination the lower apoptotic threshold for GVHD diagnosis are warranted.

Kras-Deficient T Cells Attenuate Graft-versus-Host Disease but Retain Graft-versus-Leukemia Activity.

Acute graft-versus-host disease (aGVHD) is one major serious complication that is induced by alloreactive donor T cells recognizing host Ags and limits the success of allogeneic hematopoietic stem cell transplantation. In the current studies, we identified a critical role of Kras in regulating alloreactive T cell function during aGVHD. Kras deletion in donor T cells dramatically reduced aGVHD mortality and severity in an MHC-mismatched allogeneic hematopoietic stem cell transplantation mouse model but largely maintained the antitumor capacity. Kras-deficient CD4 and CD8 T cells exhibited impaired TCR-induced activation of the ERK pathway. Kras deficiency altered TCR-induced gene expression profiles, including the reduced expression of various inflammatory cytokines and chemokines. Moreover, Kras deficiency inhibited IL-6-mediated Th17 cell differentiation and impaired IL-6-induced ERK activation and gene expression in CD4 T cells. These findings support Kras as a novel and effective therapeutic target for aGVHD.

Erdheim-Chester disease: Cytomorphologic clues for a rare histiocytic neoplasm including a distinct tigroid background pattern on smears.

We present the cytomorphologic features of Erdheim-Chester disease (ECD) from 7 patients who have a confirmed diagnosis of ECD, including correlation with the histology on the needle core biopsies. ECD is a rare multi-organ neoplastic histiocytic disorder. The most common locations of involvement are long bones, retroperitoneum, and vasculature. Cytologic preparations often show scant cellularity. Even when neoplastic histiocytes are present on smears, they may be readily overlooked as they are not typically monomorphic, and instead exhibit a variety of morphologies from epithelioid to spindled, with multinucleated giant cells variably present. To our knowledge, ours is the first description of a distinct reticular or tigroid background on smears that is variably present due to rupture of the foamy neoplastic cells. Typically, smears from a targeted mass lesion from any site showing scant polymorphous histiocytes would be regarded as non-diagnostic. A diagnosis of ECD in all cases was based on the needle core biopsy with corresponding immunohistochemical (IHC) stains and BRAF mutational analysis, except for one case in which molecular analysis was not able to be performed. We present these cases to alert practicing cytopathologists to the pitfalls related to the highly variable location, smear cellularity, and cytomorphology of ECD, which should prompt the request of dedicated tissue cores at the time of rapid on-site evaluation and trigger careful clinical-radiologic correlation, as well as consultation with hematopathology colleagues.

Biphasic squamoid alveolar renal cell carcinoma: Cytologic features of a rare entity.

Biphasic squamoid alveolar renal cell carcinoma is a newly described rare morphologic variant of papillary renal cell carcinoma. Its characteristic histomorphology and immunophenotype have been well described in the literature. Namely, BSARCC is composed of a dual-cell population with nests of larger squamoid cells surrounded by a single layer of cuboidal cells in alveolar arrangements. Invariably, the squamoid component expresses cyclin D1. More recently, MET alterations have been identified within a subset of BSARCC, raising the possibility for targeted MET inhibitor therapy. To the best of our knowledge the cytomorphologic features of BSARCC have yet to be described. Herein we correlate the cytologic features (percutaneous image-guided fine needle aspiration) of BSARCC to its corresponding histomorphology and immunophenotype (core needle biopsy).

Desmoid fibromatosis involving the pancreas: A retrospective case series with clinical, cytopathologic and radiologic correlation.

Desmoid-type fibromatosis (desmoid tumors) which involve the pancreas is an infrequent diagnosis which clinically can mimic both neoplastic and non-neoplastic lesions of the pancreas. The cytologic features of loosely cohesive cytologically bland (myo)fibroblastic cells are non-specific, however the long fascicular growth pattern and the presence of ß-catenin mutation with positive nuclear immunohistochemical staining or molecular testing allows for definitive diagnosis. While many previously reported desmoid tumors of the pancreas have been surgically resected, conservative management with a "watch and wait" approach is also an effective mode of management for these tumors. Herein, we report the largest case series of pancreatic desmoid tumors with clinical, cytopathologic, and radiologic correlation.

Cyto-histologic correlation of crystal-storing histiocytosis: Rare presentation in breast, predating diagnosis of B-cell lymphoma by two years.

Crystal-storing histiocytosis (CSH) is a rare disorder characterized by the accumulation of crystalized immunoglobulins within the cytoplasm of histiocytes. It is often associated with an underlying lymphoproliferative or plasma cell disorder. Most patients with CSH are asymptomatic in regard to the disease and are incidentally discovered. Herein we present cyto-histologic correlation of a rare example of CSH presenting with a two-year interval between original diagnosis of CSH and confirmation of a low-grade B-cell lymphoma.

Mammary analogue secretory carcinoma: A challenging case arising in a young man with radiation exposure.

Mammary Analogue Secretory Carcinoma (MASC) is a recently described salivary gland tumor frequently sampled via fine-needle aspiration. The cytologic features of MASC are not entirely distinctive and can simulate acinic cell carcinoma, but the tumor harbors an ETV6 gene rearrangement resulting in an ETV6-NTRK3 fusion gene. We present a case of MASC arising in a 31 year old man with a history of multiple radio-embolization procedures.

Eccrine angiomatous hamartoma: First case in the cytology literature.

A 34-year-old male presented with a swelling on the volar surface of the third digit of his right hand. This swelling was associated with pain and erythema. Ultrasound-guided needle biopsy was performed. Cytologic and histologic preparations together confirmed the diagnosis of a rarely encountered mixed epithelial and mesenchymal proliferation, an eccrine angiomatous hamartoma. To our knowledge, this case is the first to illustrate the cytomorphologic features of this rare lesion.

Malignant gastrointestinal neuroectodermal tumor: Cytologic, histologic, immunohistochemical, and molecular pitfalls.

Malignant gastrointestinal neuroectodermal tumor (GNET) is a rare malignant primary gastrointestinal mesenchymal tumor which can be diagnosed via fine-needle aspiration (FNA) cytology. In the context of FNA, the diagnosis requires a cell block and the use of significant resources including immunohistochemical stains and molecular testing. The differential diagnosis of GNET includes clear cell sarcoma (CCS), gastrointestinal stromal tumor (GIST), gastric schwannoma, metastatic melanoma, malignant perivascular epithelioid cell tumor (PEComa) and granular cell tumor, among others. Here we describe a case which was initially diagnosed as malignant granular cell tumor by FNA which was later revised to GNET following the finding of an EWSR1-ATF1 fusion gene rearrangement.

Evaluation of the lower histologic threshold for gastric graft versus host disease.

Data regarding the lower diagnostic threshold for gastric graft-versus-host disease is lacking. The aim of this study was to review a cohort of gastric biopsies taken to evaluate for graft-versus-host disease, and to correlate histologic findings with clinical and endoscopic evidence of graft-versus-host disease as well as biopsy findings from other locations to define a lower diagnostic threshold for gastric graft-versus-host disease. Gastric biopsies were evaluated for the maximum number of apoptotic bodies per 10 contiguous gastric pits, presence of ≥1 apoptotic body per biopsy (NIH criteria), and presence of gastric pit dropout and/or ulceration. To evaluate histologic specificity, sixty gastric biopsies from non-stem cell transplant patients were selected as a control group. Clinical information was collected from chart review. The study group consisted of 65 gastric biopsies from 52 stem cell transplant patients. The mean apoptotic count per 10 contiguous gastric pits for stem cell transplant biopsies was 1.8 (range 0-8) and for control cases 1.0 (range 0-5). Nineteen stem cell transplant biopsies (29%) had ≥1 apoptotic body per biopsy and only a single case had >6 apoptotic bodies per 10 contiguous gastric pits. When the NIH guidelines were combined with presence of at least two apoptotic bodies per 10 contiguous gastric pits, this cutoff point was significantly associated with treatment for graft-versus-host disease (OR = 9.4, 95% CI = 1.7-176.7, p = 0.04) and evidence of extraintestinal graft-versus-host disease (OR = 3.2, 95% CI = 1.1-10.7, p = 0.04). The diagnostic specificity for our proposed cutoff value is 94%. We present criteria for the lower diagnostic threshold of gastric graft-versus-host disease, which uses a lower apoptotic cutoff value than has been utilized in colonic biopsies. Although sensitivity remains a challenge for gastric graft-versus-host disease biopsies, this newly proposed cutoff provides higher specificity than NIH guidelines alone and better correlates with clinical evidence of graft-versus-host disease.

Lymphoepithelial cyst of the pancreas: A challenging diagnosis on fine needle aspiration.

Lymphoepithelial cysts (LECs) of the pancreas are rare, benign pancreatic cysts comprising approximately 0.5% of all pancreatic cysts. They occur predominantly in men in the 5th and 6th decades of life. LECs are true cysts lined by stratified squamous epithelium with adjacent subepithelial lymphoid tissue. They range in size from 1.2 to 17 cm (mean size 4.6 cm) and can arise in any part of the pancreas. 1 LEC resembles other benign and malignant pancreatic cysts clinically and radiologically. The cytomorphologic features of LECs have been described in a small number of case reports and it has been indicated that features may overlap with other benign and malignant pancreatic lesions. Herein, we report clinical, radiological, cytological and histopathological features of a pancreatic LEC in a 62-year-old male.

Intraductal papillary squamous neoplasm of the pancreas: Cyto-histologic correlation of a novel entity.

We correlate the cytologic and histologic features of a squamous-lined pancreatic cystic lesion with a complex papillary architecture and an associated KRAS mutation, which to our knowledge has not been previously described. A 69 year-old woman presented with intermittent left upper quadrant pain. CT imaging revealed a 1 cm solid lesion in the pancreatic tail with peripheral calcification. Endoscopic ultrasound-guided fine needle biopsy showed a proliferation of epithelial cells with fibrovascular cores. An immunohistochemical stain for p40 was positive in the lesional cells. A distal pancreatectomy revealed a unilocular, cystic, well-circumscribed, soft and friable mass measuring 1.0 × 1.0 × 0.8 cm. Histologically, the cyst was lined by nonkeratinizing stratified squamous epithelium with a complex papillary architecture, filling the cyst lumen. Molecular sequencing revealed a KRAS G12V missense mutation. While the lesion shared some histologic features with the previously described "squamoid cyst of the pancreatic ducts", the complex papillary architecture and presence of a KRAS mutation are unique to the entity we describe herein and we propose the name "intraductal papillary squamous neoplasm of the pancreas." Reporting the cytomorphologic features of this novel entity may help in identification of similar lesions and understanding of the clinicopathologic significance.

Gross tumor size using the AJCC 8th ed. T staging criteria does not provide prognostic stratification for neoadjuvant treated pancreatic ductal adenocarcinoma.

The 8th edition AJCC T stage criteria for pancreatic ductal adenocarcinoma (PDAC) are now size based. These criteria provide better prognostic stratification in patients without neoadjuvant therapy. Our aim was to determine if gross tumor size is prognostically significant using the 8th ed. staging criteria for neoadjuvant treated PDAC. The study included 289 patients who underwent resection for PDAC following neoadjuvant therapy. By AJCC 7th ed., there were 12 (4.2%) ypT0, 32 (11.1%) ypT1, 64 (22.1%) ypT2, and 181 (62.6%) ypT3 patients. By AJCC 8th ed., there were 12 (4.2%) ypT0, 74 (25.6%) ypT1 (6 ypT1a, 1 ypT1b, 67 ypT1c), 161 (55.7%) ypT2, and 42 (14.5%) ypT3 patients. 182 patients had negative lymph nodes and 107 had positive lymph nodes. 77 patients were ypN1 and 30 were ypN2 by 8th ed. criteria. 7th ed. T stage significantly correlated with OS (p = 0.048), while 8th ed. T stage did not correlate with OS (p = 0.13). In ypN0 patients, neither the 7th ed. or 8th ed. T stages significantly correlated with patient OS (p = 0.065 and 0.26, respectively). Higher 7th ed. T stage correlated with lymph node status (p ≤ 0.001) more strongly than 8th ed. T stage (p = 0.04). 7th ed. and 8th ed. N stage correlated with OS (p = 0.004 and p = 0.0002, respectively). By 8th ed. AJCC staging criteria, gross tumor size does not provide good prognostic stratification in neoadjuvant therapy PDAC. Mapped grossing techniques combining gross and microscopic examination to determine tumor size may provide more accurate staging of neoadjuvant treated tumors.

Colonic graft-vs.-host disease in autologous versus allogeneic transplant patients: earlier onset, more apoptosis, and lack of regulatory T-cell attenuation.

Histologic characterization of graft-vs.-host disease in autologous stem cell transplant patients has been limited. The aims of this study were to characterize colonic graft-vs.-host disease in autologous stem cell transplant patients and compare to a control group of allogeneic stem cell transplant patients, to determine whether graft-vs.-host disease can be diagnosed < 21 days post transplantation in autologous stem cell transplant recipients, and to quantify colonic T-cell populations in autologous stem cell transplant patients. Colonic biopsies taken to evaluate for graft-vs.-host disease in both allogenic and autologous stem cell transplant patients were reviewed for the maximum number of apoptotic bodies per 10 contiguous crypts. Immunohistochemical stains for CD4, CD8, and FoxP3 were performed. Clinical information was collected from chart review. The study group consisted of 122 colonic biopsies from 84 patients. Sixteen patients underwent autologous stem cell transplant and 68 allogeneic stem cell transplant. Autologous stem cell transplant patients underwent biopsy significantly earlier compared with allogeneic stem cell transplant patients (median 20 vs. 87 days, p = 0.0002), had significantly higher apoptotic counts compared with matched-related donor patients (7.5 vs. 3.9, p = 0.03), and had higher FoxP3-positive lamina propria lymphocytes counts compared to allogeneic stem cell transplant patients (9.2 vs. 5.3, p = 0.03). In patients undergoing biopsy < 21 days post transplantation, allogeneic stem cell transplant patients showed less CD8-positive lamina propria lymphocytes and a trend of less FoxP3- and CD4-positive lamina propria lymphocytes compared with autologous stem cell transplant patients. Autologous stem cell transplant patients have more prominent crypt apoptosis compared with allogenic stem cell transplant patients and do not have numerically decreased FoxP3-positive lamina propria lymphocytes. Presence of robust T-cell populations in the early period following transplantation suggest that the 21-day cutoff for diagnosis of graft-vs.-host disease is not applicable to autologous stem cell transplant patients.