International Journal of Surgical Pathology

Context. A significant portion of colorectal biopsies are performed for evaluation of polyps or polypoid lesions. Accurately identifying these lesions will promote better patient care. Objective. Review of the pathology of major colon polyps and polypoid lesions and highlight the most diagnostically useful features and their molecular biology. Data source. Review of recent literature. Conclusions. Polypoid lesions of the colon can be thought of to be under 3 broad categories: syndromic, mesenchymal, and epithelial.

We evaluated clinical parameters, histomorphology, and thyroid transcription factor 1 (TTF-1) immunoreactivity in 40 epidermal growth factor receptor (EGFR) mutation– and anaplastic lymphoma kinase (ALK) rearrangement–negative invasive pulmonary adenocarcinomas. Tumors were histomorphologically quantitated by a pulmonary pathologist and TTF-1 immunohistochemistry applied. EGFR mutation and ALK rearrangement status was determined with polymerase chain reaction/DNA sequencing and fluorescence in situ hybridization, respectively. Treatment response was related to type of treatment (P < .005) and clinical stage (P = .001). EGFR mutation– and ALK rearrangement–negative pulmonary adenocarcinomas containing papillary/micropapillary histology showed greater morphologic heterogeneity (P < .001), greater TTF-1 immunoreactivity (P = .004), and were more common in treatment responders (P < .05). These findings support that patients with pulmonary adenocarcinomas that are subject to nontargeted therapies may respond to treatment as a function of tumor cell differentiation with TTF-1 as a potential biomarker of this response.

ΔNp63 (henceforth simply p40) is a squamous/basal-type biomarker corresponding to nontransactivating (non-TA) isoforms of p63 gene. Its prospective relevance as driver biomarker in lung cancer has not yet been thoroughly investigated. In all, 72 adenocarcinomas (ADs), 27 squamous cell carcinomas (SQCs), 13 pleomorphic carcinomas (PLCs), 10 small-cell lung carcinomas (SCLCs), 5 large-cell neuroendocrine carcinomas (LCNECs), 5 adenosquamous carcinomas (ADSQCs), 3 large-cell carcinomas with basaloid features (B-LCC), 2 carcinoids, 2 carcinosarcomas (CS), 2 salivary-gland type tumors (SGTTs) of the lung, and 5 pleural malignant epithelioid mesotheliomas (MEMs) were prospectively diagnosed by morphology and verified by immunohistochemistry for p40, p63, and thyroid transcription factor 1 (TTF1). Histological scores (HS) were devised by multiplying the percentage of immunoreactive cells (0 to 100%) by immunostaining intensity (low = 1 vs strong = 2, according to internal controls). There was a nonrandom distribution of p40 across the diverse tumor groups and cell differentiation lineages, with p40-HS > 100 closely paralleling squamous or myoepithelial carcinomas (SQC, B-LCC, SQC-containing PLC, ADSQC with predominant SQC, SGTT), and p40-HS ≤ 10 pinpointing AD, AD-containing PLC, or CS and neuroendocrine (NE) tumors. At variance, p63-HS was significantly higher than p40 in AD (P < .0001) and NE tumors (P = .0156), with positive predictive value being 83% and 95% and overall accuracy being 95% and 99%, respectively. Also, TTF1 was shared by gland-differentiated and NE tumors. MEM cases were always negative for all biomarkers. The HS-guided assessment of p40 allowed an effective orientation among thoracic malignancies at the level of individual tumor patients thereby contributing to prospectively realize a driver, holistic approach to cancer characterization.

The objectives of this study were to identify HER2 prevalence in gastric cancer and correlate it with location, phenotype, and follow-up. Consecutive gastric cancer patients with tissue blocks, gross data, and follow-up data, were submitted to immunohistochemistry (IHC) with HercepTest. Chromogenic and fluorescence in situ hybridization was performed in IHC-positive tumors. A total of 269 patients were included with a median age of 61 years. In 172 gastrectomized patients, histotypes were diffuse (72, 41.8%), intestinal (63, 36.6%), and mixed (37, 21.5%). HER2 IHC expression was 0 in 167, 2+ in 2, and 3+ in 3 tumors. Only endoscopic biopsies were available in 97 patients and HER2 IHC expression was 0 in 88, 1+ in 3, 2+ in 4, and 3+ in 2 patients. In all, 10/269 (3.7%) had HER2 amplification. Amplified tumors were intestinal adenocarcinomas located throughout the different regions of the stomach. Heterogeneity was documented in 4 widely sampled tumors. HER2 amplification was restricted to the intestinal phenotype. It is a rare event and its screening should be driven by gastric cancer histotype.

Even though apoptotic bodies (ABs) are frequent in colorectal adenomas, their relevance has been covered only in a few studies. Focal active cryptitis (FAC) is a well-known manifestation of several etiologies; however, its prevalence and significance in colonic adenomas were not scrutinized. Likewise, whether the neutrophilic infiltrate of the lamina propria (LP) in colonic adenomas has a clinical or pathologic significance was not previously studied. We attempted to investigate the prevalence and importance of ABs in the cryptal epithelium and of neutrophils in the form of FAC and in the form of LP infiltrates in conventional colorectal adenomas. We conducted a retrospective review study over a 6-year period. We collected 223 conventional adenomas from 156 patients. We studied the interrelationship between these 3 histologic parameters and their potential association with other clinical and pathologic variables. Comparison controls included normal colonic mucosa, hyperplastic polyps, serrated adenomas, and flat adenomas. We found 91 (41%) adenomas to have crypt apoptosis, 40 (18%) to have FAC, and 69 (31%) to have neutrophilic infiltrate of the LP. We found ABs to be more frequent in high-grade adenomas. LP neutrophilic infiltrate was significantly associated with high-grade adenomas and in high-grade adenomas with invasive foci. In contrast, FAC was not associated with high-grade adenomas and was secondary to bowel preparations and drugs. Crypt apoptosis and LP neutrophils might have a potential prognostic value in predicting the biologic behavior of colonic adenomas. FAC in adenomas is a nonspecific finding of no prognostic significance and is related to external stimuli.

Enumeration of crypt apoptotic bodies (AB) is used in the diagnosis of acute cellular rejection (ACR) in small bowel allografts. Due to differing definitions, there is a potential for variation in AB numbers between pathologists that may affect diagnosis. Thirty biopsies from allografts were obtained: 10 negative for ACR, 10 indeterminate, and 10 with mild ACR. Three pathologists blindly reviewed each case twice and counted the maximal AB number per 10 crypts. Intraobserver kappa ranged from 0.423 to 0.913 and interobserver kappa from 0.478 to 0.686 depending on AB definition. Intraobserver diagnosis agreement based on classical AB number occurred in 81 of 90 instances (90%) and in 77 of 90 using the liberal definition (85%), P < .01). There was substantial intraobserver and moderate to substantial interobserver agreement in crypt AB counts. However, both intraobserver and interobserver variability would have led to diagnostic discrepancies in a small subset of cases.

Melanosis coli is a well-known occurrence in colonic biopsies. The condition is, however, reportedly absent in both neoplastic and hyperplastic colonic polyps. Herein, we describe its occurrence in 10 hyperplastic coloniuc polyps, some of which showed melanosis in adjacent biopsied mucosa, and 2 colonic adenomata.

Extramedullary hematopoiesis (EMH) develops as a compensatory mechanism associated with hematologic processes but it may occur in association with chemotherapy. Three cases of EMH arising in axillary lymph nodes following neoadjuvant therapy for breast carcinoma are reported herein. Three women ranging in age from 41 to 47 years presented with unilateral breast masses measuring 0.6 to 4.0 cm in greatest dimension and were diagnosed with infiltrating ductal carcinoma, grade III by core needle biopsies. Two of the tumors were triple negative and one was estrogen receptor positive. All patients subsequently received neoadjuvant therapy followed by lumpectomies. No residual carcinoma was identified in postchemotherapy breast resection specimens. One patient underwent a sentinel lymph node procedure, the second patient an axillary lymph node dissection, and the third patient had a core biopsy of an enlarged axillary lymph node. The patient that underwent axillary lymph node dissection had metastatic carcinoma in one of her lymph nodes. Foci of EMH consisting of myeloid, erythroid, and megakaryocytic precursors were present within the nodal parenchyma and/or subcapsular sinuses of axillary lymph nodes of all three cases. Megakaryocytes were immunoreactive with factor VIII, erythroid elements with Glycophorin and myeloid precursors with myeloperoxidase. With increasing use of neoadjuvant therapy for breast carcinoma, EMH within lymph nodes is more likely to be encountered. Hematopoietic precursors present in lymph nodes may potentially be misdiagnosed as metastatic tumor cells, particularly as lobular carcinoma or metaplastic carcinoma. Therefore, caution should be exercised when evaluating axillary lymph nodes in the clinical setting of neoadjuvant therapy for breast carcinoma.

Retrorectal or presacral tumors are very rare. We report a unique case of a retrorectal tumor with neuroendocrine differentiation, consisting of high- and low-grade components. A 53-year-old woman treated for a perianal abscess at another clinic was referred to our hospital for continued anal pain. Digital rectal examination identified a soft tumor with a smooth surface in the lower rectum. Pelvic computed tomography and magnetic resonance imaging detected a large cystic tumor measuring 8 cm in diameter in the retrorectal space of the pelvis. The border between the tumor and rectal wall, levator ani and vaginal wall was obscure. Fine-needle aspiration cytology was highly suggestive of carcinoma. Abdominoperineal resection was performed, and the tumor was histologically diagnosed as a neuroendocrine carcinoma based on immunohistochemical staining. No previous case has been reported with cystic growth of a neuroendocrine carcinoma in the retrorectal space.

Endometrial stromal sarcoma is an uncommon tumor representing 0.2% of all uterine neoplasm and 15% to 26% of uterine sarcomas. Endometrial stromal sarcoma has a gross appearance as single nodule, multiple masses, or a poorly demarcated lesion with occasional cystic degeneration; rarely, it shows a cystic multilocular feature. We report 2 cases of endometrial stromal sarcoma with a prominent cystic appearance, forming multilocular cystic mass, detected by ultrasonography. The differential diagnosis among multycistic endometrial stromal sarcoma and cystic uterine tumors might be very difficult.

Crystals and crystalloids may be seen in salivary glands in association with tumors and cysts. Rarely, crystalloids may lead to granulomatous reaction mimicking neoplasm and infectious diseases. We present the case of an 81-year-old man with right parotid gland swelling and a clinical and radiological diagnosis of tumor. A granulomatous inflammation was seen on intraoperative pathology. On final pathology, the parotid gland showed multiple granulomas with central cavitation and palisading histiocytes with eosinophilic intracytoplasmic and extracellular crystalloids. The crystalloids were variably shaped, needle-like, polyhedral, rhomboid, rectangular and irregular, nonpolarizable, nonbirefringent, and nonrefractile and were orange-red with trichrome and bluish-purple with Brown and Brenn stain. Remnants of a duct lining within the lesion suggested a granulomatous response to ruptured cyst contents releasing secretions supersaturated in proteins and their precipitates.

Kikuchi–Fujimoto disease (KFD), a histiocytic necrotizing lymphadenitis (HNL), characteristically presents as cervical lymphadenopathy in young Asian women. Most resolve spontaneously with rare recurrences described. We report a patient with biopsy-proven recurrence of KFD-like HNL after almost 8 years and analyze 65 additional published cases with recurrences. While those with recurrences similarly affect young (average age = 27 years), Asian (80%) women (76%), 73% had multiple sites of involvement and 32% of those tested had underlying autoimmune conditions. Our case is unusual with respect to the following: (a) Age: 50 years, the oldest among the reported patients with recurrences. (b) Race: African descent, with only 3 others reported with recurrent HNL. Of these 4 cases, 2 had underlying autoimmunity. (c) Underlying condition: Her clinical and laboratory features were best felt to represent Sjögren’s syndrome (SjS). Only 2 other cases of SjS-associated HNL have been reported; in 2 recently reported cases SjS developed subsequently.

Kaposiform hemangioendothelioma (KHE) is presently classified as a vascular neoplasm of intermediate malignant potential. The clinical course of large, deep-seated tumors is frequently complicated by consumptive coagulopathy and life-threatening hemorrhage, while superficial tumors tend to behave in an indolent manner, with no known reports of distant metastasis. We describe an unusual example of KHE occurring as an incidental microscopic finding, within a background of extensive lymphangioma-like changes. The patient underwent 4 intralesional excisions over a period of 6 years, and the Kaposiform component accounts for less than 5% of the overall tissue excised. The patient remains clinically well with residual disease 5 years after conservative surgery, and there has been no evidence of regional or distant metastasis. Based on existing literature, it appears doubtful that KHE has any metastatic potential at all, which calls into question the appropriateness of its place in the spectrum of malignant vascular neoplasms.

We report a case of a 68-year-old female patient who developed hemophagocytic lymphohistiocytosis (HLH) secondary to peripheral T-cell lymphoma (PTCL) not otherwise specified (NOS) that developed in the setting of treatment-resistant B-cell small lymphocytic lymphoma/chronic lymphocytic leukemia (SLL/CLL). The patient’s B-cell lymphoma had a good initial response to chemotherapy for 4 years, after which it became less responsive and was thought to have undergone transition to a higher-grade lymphoma. Different regimens of chemoradiotherapy were then tried with modest response until the patient presented 3 years later with signs and symptoms of HLH. The patient died 1 month later, and an autopsy was performed. Significant para-aortic lymphadenopathy and splenomegaly were found. Microscopic, immunohistochemical and molecular evaluations confirmed the presence of composite B-cell and T-cell lymphoma in the para-aortic enlarged lymph nodes. Bone marrow examination showed hemophagocytosis, and the liver demonstrated infiltration by activated macrophages with hepatocellular necrosis. This report highlights the importance of searching for a possible underlying T-cell lymphoma in light of HLH. Different theories have been proposed to explain the rare occurrence of concurrent B- and T-cell lymphomas, but the development of HLH in this patient highlights the importance of immune dysregulation as a proposed mechanism to explain some cases of composite lymphomas. A review of the literature and discussion of the relative merits of these hypotheses are presented in the context of this case.