Comparative Immunohistochemical Analysis of Macrophage Phenotypes in Cutaneous Sarcoid Granuloma, Suture Granuloma, and Lipogranuloma.

ABSTRACT: Granulomas are composed of a heterogeneous population of resident and recruited macrophages according to the type of lesion, extent of injury, and local tissue environment (eg, involved site and interaction with infiltrating lymphocytes). Although macrophage phenotypes in various types of granulomas have been previously described, the experimental conditions varied across studies, precluding a comparative and comprehensive understanding of granulomas. This study was conducted to comparatively analyze the expression of markers of the M1 and M2 phenotypes in macrophages that compose various types of granulomas, including epithelioid lesions, under strict conditions. Surgical specimens of cutaneous sarcoidosis (11 lesions), suture granuloma (10 lesions), and subcutaneous lipogranuloma (12 lesions) were immunohistochemically stained for CD11c, CD206, CD163, and CD10. The expression of these markers in macrophages composing each type of granuloma was scored and statistically analyzed. Granuloma macrophages were mostly immunoreactive for CD11c and CD206 in all the examined cases, although many intermingling CD206-negative cells were observed in 5 cases of lipogranuloma. CD163 and CD10 were diffusely expressed in macrophages composing suture granuloma and lipogranuloma, whereas they were not expressed in epithelioid cells in cutaneous sarcoidosis. Meanwhile, "interstitial" macrophages around epithelioid granulomas revealed moderate to marked CD163 expression in 7 lesions of cutaneous sarcoidosis. These results indicate significant differences of expression of CD163 and CD10 between cutaneous sarcoidosis and suture granuloma/lipogranuloma; CD163 and CD10 are downregulated after the epithelioid transformation of macrophages in cutaneous sarcoidosis.

Phosphoglyceride crystal deposition disease involving adnexa uteri: a case report with histogenetic consideration.

We present a rare case of phosphoglyceride crystal deposition disease (PCDD), as a gynecologic disease, with reference to histogenesis of crystal deposition. An 84-year-old woman, who had undergone simple hysterectomy for uterine leiomyoma 44 years previously, presented with multiple masses in the bilateral adnexa and the pelvic wall. The bilateral adnexal tumors were resected. The masses histologically revealed a foreign-body granuloma composed of numerous tiny, radially arranged needle-like crystal lumps surrounded by multinucleated giant cells and macrophages. The crystals showed birefringence under polarized light and were positive for gold hydroxamic acid stain, and the tumor was thus diagnosed as PCDD. The masses revealed central cystic changes due to old hemorrhage, which contained crystal lumps without foreign-body reaction or birefringence. The present case demonstrated for the first time that phosphoglyceride crystals developed in old hemorrhagic foci, although it was not confirmed whether the old hemorrhagic foci were formed after hysterectomy or due to endometriosis.

Immunohistochemical Localization of Phosphorylated and Unphosphorylated Form of ß-catenin With Regard to Shadow Cell and Squamous Differentiation in Cutaneous Pilomatricoma.

Pilomatricoma usually contains a mutation in CTNNB1 that encodes ß-catenin (BC). It also shows nuclear accumulation of BC protein, which plays an important role in tumorigenesis of pilomatricoma. In vitro studies have indicated that mutant BC protein is unphosphorylated and shows nuclear accumulation, but this theory has not been confirmed in various tumors with CTNNB1 mutation. We examined immunohistochemical localization of phosphorylated BC (pBC) and unphosphorylated BC (npBC) with regard to the modes of cell death or differentiation in 25 cases of pilomatricoma. As for the component showing shadow cell differentiation, BC was detected in cytoplasm/nucleus and along cell membrane in basaloid cells, whereas only in the latter in transitional cells in all cases. Meanwhile, npBC was localized along cell membrane of transitional cells, but not in basaloid cells, nor in nucleus of any components. The components with squamous differentiation also revealed the staining patterns similar to those seen in shadow cell differentiation in some cases. pBC was found in some cell fragments in the amorphous debris containing apoptotic bodies among shadow cell nests. These results suggested that npBC plays an important role in cell adhesion during differentiation and that pBC expression is associated with apoptosis of basaloid cells in pilomatricoma. BC accumulated in the nucleus was not immunoreactive for npBC possibly due to post-translational modification or conformational changes that resulted in loss of or masked antigenicity when BC is assumed to be unphosphorylated.

[Case of Asymptomatic Multiple Bone and Bone Marrow Metastases in Gastric Signet-Ring Cell Carcinoma].

A 57-year-old man visited our hospital for evaluation of an abnormal shadow identified on chest radiography. Chest computed tomography findings suggested diffuse bone metastases in the thoracic spine and the bilateral ribs. Notably, 18- fluoro-deoxyglucose positron emission tomography revealed no evidence of the primary tumor. Esophagogastroduodenoscopy revealed a small flat depressed lesion in the greater curvature of the gastric angle. Histopathological examination of this specimen revealed a signet-ring cell carcinoma. Histopathological examination of a biopsy obtained from the right iliac bone revealed a signet-ring cell carcinoma similar to that observed in the gastric mucosa. He was diagnosed with a gastric signetring cell carcinoma with multiple bone and bone marrow metastases. Cervical metastases caused gradual worsening of respiratory functions, necessitating artificial ventilation. He died of sudden ventricular tachycardia on the 36th day. Clinicians should be aware of the features of primary gastric cancer with bone and bone marrow metastases for early diagnosis and prompt treatment.

Clinical significance of serum PSA in breast cancer patients.

BACKGROUND: Recent preclinical data suggest that androgen receptor (AR) signaling plays a significant role in subsets of breast cancer. Clinical trials testing AR-targeting therapies in breast cancer have been conducted. Assessment of AR-signal in breast cancer tissue maybe useful for treatment selections. Prostate specific antigen (PSA) is the product of an androgen-responsive gene. Serum PSA (sPSA) can be detected in women by a highly sensitive assay although the concentration is much lower than that observed in males. We investigated if sPSA reflects tumor biology, including AR signaling in breast cancer patients. METHODS: In this study, 132 healthy controls and 144 breast cancer patients were enrolled. sPSA was evaluated by the chemiluminescent enzyme immunoassay (CLEIA) method. Correlations between sPSA and the various clinicopathological factors were analyzed. RESULTS: In post-menopausal state, sPSA detection rate was significantly higher in breast cancer patients compared with controls (27.4% vs 11.3%: p = 0.0090), but not in the whole cohort (29.2% vs 25.8%: p = 0.5265) or pre-menopausal subgroup (37.0% vs 42.6%: p = 0.6231). In post-menopausal breast cancer cases, higher sPSA value was associated with clinic-pathological factors including the expression of AR protein in primary legion. In a correlation analysis of quantitative data limited to post-menopausal metastatic breast cancer (MBC), sPSA was positively, albeit weakly correlated with clinic-pathological features including serum testosterone levels and AR positivity. CONCLUSIONS: Our data suggest that sPSA may reflect tumor biological properties including AR activity in post-menopausal breast cancer.

[A Case of Stromal Sarcoma of the Breast Showing Rapid Increase].

An 83-year-old woman visited our hospital with a mass on her right breast mass. Breast ultrasonography revealed a tumorous lesion approximately 30mm in diameter in the right E region. Fibrous tumor was suspected from core needle biopsy. Since surgery for definite diagnosis was not desired, she was followed. Seven months after the first visit, skin redness, pain, and rapid increase in tumor size was consciously recognized, which prompted a reconsultation. The tumor diameter rapidly increased to 74 mm, and a total right mastectomy was performed as a semi-emergency procedure. Necrotic and hemorrhagic lesions were mixed in a mottled state in the cleaved surface of the excised specimen, and the pathological diagnosis was stromal sarcoma mainly comprising of fibrosarcoma components. Stromal sarcoma of the breast lacks the epithelial component of a malignant phyllodes tumor, and effective systemic therapy has not been established; therefore, cases with local recurrence or distant metastasis result in poor prognosis. Since we encountered a case of stromal sarcoma of the breast that showed a rapid increase after several months, we will provide a report with some literature consideration.

[A Case of Chordoma of the Sacrum Treated with Pazopanib].

A-70-year-old man with chordoma of the sacrum was treated with pazopanib (initially 400 mg/day, upto 800 mg/day). After 2 months of treatment, a significant tumor reduction was achieved and the patient was able to sit down easily. Therefore, the pazopanib therapy was continued. He had 14 months of progression-free survival.

A very rare case of spontaneous regression of basaloid squamous cell carcinoma of the lung.

Spontaneous regression of non-small cell lung cancer is relatively rare. Here, we present a very rare case of spontaneous regression of lung cancer which occurred in a patient with basaloid squamous cell lung cancer. To the best of our knowledge, this is the first report of such a case. A 76-year old man was referred to our hospital with nodules in the right upper lobe determined by chest computed tomography. The nodules spontaneously regressed during follow-up. Two years later, the tumor had regrown and the patient subsequently underwent surgery. The pathological findings showed basaloid squamous cell carcinoma. Stimulation of the immune system was considered to be the cause of the spontaneous regression and CD-8 positive and CD-4 positive lymphocytes might play an important role.

Simultaneous Acquisition of T790M Mutation and SCLC Transformation during Targeted Therapy in EGFR-Mutated Lung Adenocarcinoma: A Rare Case Report.

BACKGROUND Various resistance mechanisms of the epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) have been reported, and approximately half of the cases show a T790M point mutation as resistance to EGFR-TKI. In addition, 3-14% of cases of non-small cell lung cancer transform into small cell lung carcinoma (SCLC) during treatment. However, there are few reported cases in which 2 mechanisms of resistance have been observed simultaneously. This report describes a 66-year-old man with initial presentation of stage IIA right-sided lung adenocarcinoma with EGFR gene exon 21 L858R mutation and 3 years of stable disease. During treatment with erlotinib, the patient developed SCLC and adenocarcinoma with EGFR exon 21 L858R and exon 20 T790M mutation. CASE REPORT A 66-year-old man underwent right pneumonectomy plus nodal dissection 2a for right hilar lung cancer and was diagnosed with an EGFR exon21 L858R mutated lung adenocarcinoma. Three years later, pleural dissemination was observed in the right chest wall. Although erlotinib was continued for 52 months, new metastases to the right ribs were detected. Chest wall tumor resection was performed. Based on the World Health Organization classification, the patient was diagnosed with combined SCLC, with EGFR exon21 L858R and exon20 T790M mutation. The patient received 4 cycles of carboplatin plus etoposide, 14 cycles of amrubicin, and 2 cycles of irinotecan. Chemotherapy continued for 25 months. CONCLUSIONS Long-term survival was achieved by chemotherapy after transformation. Since EGFR mutation-positive lung cancer shows a variety of acquired resistances, it is important to consider the treatment strategy of performing re-biopsy.

[A case of pulmonary pleomorphic carcinoma treated with S-1 following radiotherapy].

Pleomorphic carcinoma is a rare malignancy of the lung. Here we present a 68-year-old man who was admitted to our hospital for examination of an abnormal radiogram of the chest. The radiogram revealed a large mass in the right lung field. A chest computed tomographic (CT) scan demonstrated a nonsegmentalmass like consolidation. Percutaneous CT-guided fine-needle needle biopsy from the lung was performed, and the specimen demonstrated pulmonary pleomorphic carcinoma. The patient was initially treated with two courses of cisplatin (CDDP) and docetaxel (DOC), and still showed progressive disease (PD). Therefore, we administered S-1 following radiotherapy. The chest CT revealed partial response after 4 months. We experienced a pulmonary pleomorphic carcinoma which showed a response to salvage chemotherapy with S-1.

Disseminated carcinomatosis of the bone marrow caused by granulocyte colony-stimulating factor: A case report and review of literature.

BACKGROUND: Disseminated carcinomatosis of the bone marrow (DCBM) is a widespread metastasis with a hematologic disorder that is mainly caused by gastric cancer. Although it commonly occurs as a manifestation of recurrence long after curative treatment, the precise mechanism of relapse from dormant status remains unclear. Granulocyte colony-stimulating factor (G-CSF) can promote cancer progression and invasion in various cancers. However, the potential of G-CSF to trigger recurrence from a cured malignancy has not been reported. CASE SUMMARY: A 55-year-old Japanese woman was diagnosed with Ewing sarcoma localized on the fifth lumbar vertebrae 6 years after curative gastrectomy for T1 gastric cancer. After palliative surgery to release nerve compression, pathological diagnosis of the resected specimen was followed by curative radiation and chemotherapy. During treatment, G-CSF was administered 32 times for severe neutropenia prophylaxis. Eight months after completing definitive treatment, she complained of severe back pain and was diagnosed as multiple bone metastases with DCBM from gastric cancer. Despite palliative chemotherapy, she died of disseminated intravascular coagulation 13 d after the diagnosis. Immunohistochemical examination of the autopsied bone marrow confirmed a diffuse positive staining for the G-CSF receptor (G-CSFR) in the relapsed gastric cancer cell cytoplasm, whereas the primary lesion cancer cells showed negative staining for G-CSFR. In this case, G-CSF administration may have been the key trigger for the disseminated relapse of a dormant gastric cancer. CONCLUSION: When administering G-CSF to cancer survivors, recurrence of a preceding cancer should be monitored even after curative treatment.

Primary spindle cell tumor originating from the liver that was difficult to diagnose.

BACKGROUND: It has been reported that hepatocellular carcinoma (HCC) with spindle cell tumor accounts for 1.8% of all HCCs, but spindle cell tumors that do not show an obvious conventional HCC are extremely rare. In this report, we describe a case of resection of a primary spindle cell tumor of the liver that was difficult to diagnose. CASE PRESENTATION: A 75-year-old man presented with fever and right chest pain. He was suspected of a giant primary diaphragmatic tumor of extrahepatic origin by imaging studies. The preoperative differential diagnosis included benign masses such as myxoid sarcoma and schwannoma, and we planned a diaphragmatic resection. Intraoperatively, however, dissection of the tumor from the liver was not possible, requiring an extended right posterior segmentectomy with combined resection of the diaphragm. The patient had a good postoperative course and 1 year has passed since the surgery with no recurrence. The pathology showed that the mass was located just below the hepatic capsule/parenchymal region and was adherent to the diaphragm, but there was no continuity. The morphology suggested a low-grade mesenchymal tumor such as a solitary fibrous tumor and perivascular epithelioid cell tumor, but immunostaining was negative, making the diagnosis difficult. Although some areas of high proliferative activity were observed, finally, the diagnosis of primary spindle cell tumor of the liver with smooth muscle differentiation was made based on the positive results of muscle markers such as αSMA, desmin, and h-caldesmon. CONCLUSIONS: Spindle cell tumor arising from the liver is so rare that preoperative and pathological diagnosis is often difficult to reach. Although further studies are needed to elucidate and better understand this uncommon clinical entity, we consider that complete resection is necessary for the above case, which may contribute to long-term survival.

Comparative immunohistochemical analyses on the modes of cell death/keratinization in epidermal cyst, trichilemmal cyst, and pilomatricoma.

Keratinization is a kind of cell death called terminal differentiation and includes various patterns such as epidermal keratinization (EK), trichilemmal keratinization (TK), and shadow cell differentiation (SCD), whereas these have not been comparatively investigated from a standpoint of cell death. In the present study, surgically extirpated specimens of epidermal cyst, trichilemmal cyst, and pilomatricoma (10 cases in each) were subjected to immunohistochemistry for single-strand DNA (ssDNA), gamma-H2AX, cleaved caspase-3, cleaved lamin A, caspase-14, and CD138 to compare the modes of cell death and keratinization pattern. Transitional cells in pilomatricoma were immunoreactive, although not in whole part, for ssDNA and gamma-H2AX, and negative for cleaved caspase-3 and cleaved lamin A. Epidermal and trichilemmal cyst were negative for these 4 markers, except for ssDNA or cleaved lamin A in a small number of parakeratotic cells in a few cases. The keratinizing component showed caspase-14(+)/CD138(-) in epidermal cyst, caspase-14(-)/CD138(+) in trichilemmal cyst, and caspase-14(-)/CD138(-) in pilomatricoma. These results indicate that EK, TK, and SCD have a common property of apoptosis-like programmed cell death without caspase-3 activation or nuclear fragmentation. Meanwhile, they show different characteristics one another as follows: (A), DNA double-strand breaks occur in the transitional cells of SCD but not in EK/TK; and (B), EK, TK, and SCD can be distinguished by expression pattern of caspase-14 and CD138 in the keratinizing component.

[A case of rectal mucosa-associated lymphoid tissue lymphoma (MALT) successfully treated by radiation therapy].

A 33-year-old woman had hematochezia for 5 months. A total colonoscopy showed an easily-bleeding elevated lesion with a nodular lesion in the lower rectum. Histological findings of a conventional biopsy from the lesion showed MALT (mucosa-associated lymphoid tissue) lymphoma and she was diagnosed as stage I. The monoclonality of B-cells was not detected by polymerase chain reaction products for immunoglobulin heavy chain. We selected antibiotic therapy because Helicobacter pylori was detected in culture of the patient's gastric biopsy specimens. The antibiotic therapy was successful, but her symptoms worsened. We therefore gave her with 30 Gy radiation therapy. She recovered a month after the radiation. Histological complete remission was confirmed 4 months after the radiation. Adverse events of the radiation therapy included anal pain for 1 month and premature ovarian failure. Radiation therapy may be useful for localized rectal MALT lymphoma.

Sebaceous carcinoma of the breast predominantly characterized by intraductal growth: a case report.

BACKGROUND: Sebaceous carcinoma (SC) is frequently classified as periocular or extraocular. Extraocular SC is rare and mainly occurs in the head and neck, the major salivary glands, or oral mucosa. SC of the breast, lung, and ovary is particularly rare, and the few cases of SC of the breast predominantly exhibit intraductal growth. CASE PRESENTATION: A 47-year-old Japanese woman was referred to our hospital with accumulated polymorphic calcification in the left breast which was detected using mammography. Ultrasonography revealed an irregular 13-mm mass in the left breast, and analysis of a core needle biopsy revealed noninvasive ductal carcinoma. Total mastectomy and sentinel lymph node biopsy were performed. Histopathology demonstrated that carcinoma in situ (CIS) represented a significant lesion, and the cytoplasm of tumor cells was clear with numerous minute vacuoles. Immunohistochemical analysis demonstrated that most tumor cells expressed adipophilin. Together, these findings led to a diagnosis of SC, mainly comprising CIS. CONCLUSIONS: We encountered a rare case of SC of the breast with predominant CIS.

Endoscopically Observed Outer Membrane Color of Chronic Subdural Hematoma and Histopathological Staging: White as a Risk Factor for Recurrence.

Endoscopic treatment for chronic subdural hematoma (CSDH) has been reported, but endoscopic findings of CSDH have not been thoroughly investigated. This study aimed to elucidate the relationship between endoscopic findings and CSDH recurrence. Furthermore, it examined the association between Nagahori's histopathological staging of CSDH and outer membrane color. Here, we retrospectively analyzed the operative videos of 70 patients with CSDH. The endoscopic findings were investigated, and their correlations with CSDH recurrence, the reduction ratio of the midline shift, and hematoma thickness on day 30 after the operation were analyzed. The outer membrane was white in 21 cases, yellow in 25 cases, and red in 24 cases. CSDH recurred in three (4.2%) patients, all of whom had a white outer membrane (adjusted odds ratio, 18; 95% confidence interval, 1.6-20.6; P = 0.007). The other endoscopic findings were not significantly related to CSDH recurrence, extent of the reduction ratio of the midline shift, or hematoma thickness. The outer membrane colors of white, red, yellow, and white almost corresponded to the histopathological staging from type I to IV in order. Our findings suggest that a white outer membrane is a risk factor for recurrence; these colors may represent the extent of inflammation related to the evolution of CSDH estimated from the histopathological findings.

Changes in expression of bile canalicular CD10 and sinusoidal CD105 (endoglin) in peritumoral hepatic tissue.

UNLABELLED: AIMS AND BACKGROUND; Hepatic tissues, including bile canaliculi and sinusoids, around primary or metastatic tumors are destructed and regenerate associated with tumor growth, and may show some phenotypic changes. The present study was undertaken to examine the expression of CD10 in bile canaliculi [CD10(BC)] and CD105 (endoglin) along hepatic sinusoids [CD105(HS)] in peritumoral hepatic tissue (PTH). METHODS: Fifty samples of resected liver bearing hepatocellular carcinoma (HCC) or metastatic carcinoma were immunostained for CD10 and CD105. The immunoreactivity for CD10(BC) and CD105(HS) in the background hepatic tissue of tumors and PTH was scored separately. RESULTS: CD10(BC) was moderately or markedly expressed in the background hepatic tissue without chronic hepatitis or cirrhosis in most of the cases, and was significantly downregulated in chronic hepatitis and cirrhosis. CD105(HS) was negative or minimally positive in most of the cases of hepatic tissue bearing metastatic carcinoma, and showed a significant increase in chronic hepatitis and cirrhosis. Compared with the background, PTH revealed significantly decreased CD10(BC) staining irrespective of HCC or metastatic carcinoma, and showed belt-like CD105(HS) expression in 66.7% of the cases of metastatic carcinoma and in 88.6% of those with HCC. CONCLUSIONS: These data indicate that the expression patterns of CD10(BC) and CD105(HS) in PTH are similar to those in chronic hepatitis and cirrhosis, which may be caused by persistent injury and resultant regeneration of hepatic tissue.

[A case of peritoneal serous papillary adenocarcinoma].

A78-year-old female was admitted to our hospital with anorexia due to ascites. We were not able to diagnose by cytological diagnosis. For a definite diagnosis she underwent an open biopsy. Histological findings revealed observable papillary adenocarcinoma with psammoma body, carcinoma cells were positive for Ber-EP4 on immunostaining, and ovaries were normal. Thus, we made a diagnosis of peritoneal serous papillary adenocarcinoma. She was treated by intraperitoneal administration of CDDP(20 mg/day: day 1, every four weeks). Ascites vanished and CA125 was within the normal range. There was no recurrence after 3 years, but Virchow's lymph node metastasis occurred. The patient is still alive 12 months after metastasis with CDDP intraperitoneal administration.

Thoracoscopic resection of a cystic seminoma of the mediastinum.

Mediastinal seminoma is an uncommon tumor that accounts for 25% of primary mediastinal germ cell tumors, which in turn comprise fewer than 5% of all germ cell tumors. Although CT normally shows a solid, lobulated tumor, mediastinal cystic seminoma has rarely been described. Here, we report a 24-year-old man who presented with a mediastinal cystic tumor that was resected after an 18-month delay via video-assisted thoracoscopic surgery while in the supine position; the procedure involved lifting the chest wall with a subcutaneous Kirschner wire. Pathological examination revealed a mediastinal cystic seminoma. No evidence of recurrence has been noted during 25 months of follow-up. Mediastinal cystic seminoma should be considered in the differential diagnosis of cystic lesions of the mediastinum. Moreover, video-assisted thoracoscopic resection may be an appropriate option for the diagnosis and treatment of such lesions.