Cancer during pregnancy has been associated with (pathologically) small for gestational age offspring, especially after exposure to chemotherapy in utero. These infants are most likely growth restricted, but sonographic results are often lacking. In view of the paucity of data on underlying pathophysiological mechanisms, the objective was to summarize all studies investigating placental pathology related to cancer(treatment). A systematic search in PubMed/Medline, Embase (OVID) and SCOPUS was conducted to retrieve all studies about placental pathology in cancer during pregnancy or after cancer treatment, published until August 2020. The literature search yielded 5784 unique publications, of which 111 were eligible for inclusion. Among them, three groups of placental pathology were distinguished. First, various histopathologic changes including maternal vascular malperfusion have been reported in pregnancies complicated by cancer and after cancer treatment exposure, which were not specific to type of cancer(treatment). Second, cancer(treatment) has been associated with placental cellular pathology including increased oxidative damage and apoptosis, impaired angiogenesis and genotoxicity. Finally, involvement of the placenta by cancer cells has been described, involving both the intervillous space and rarely villous invasion, with such fetuses are at risk of having metastases. In conclusion, growth restriction is often observed in pregnancies complicated by cancer and its cause can be multifactorial. Placental histopathologic changes, cellular pathology and genotoxicity caused by the cancer(treatment) may each play a role.

Placental metastasis of maternal neoplasms is well documented in solid tumors, unlike hematologic neoplasms. We reviewed placental findings from deliveries complicated by maternal hematologic neoplasms exploring the prevalence and patterns of placental transmission and insufficiency. In the 8-yr study period, 11 cases were analyzed. Acute myeloid leukemia was the most common diagnosis (4/11, 36%). Seven cases (63%) showed no evidence of placental spread of neoplasm, while four cases (36%) showed placental spread, restricted to the maternal compartment. Maternal vascular malperfusion was documented in 8/11 (72%) cases. Neonatal follow up was available in 10 cases, all children were alive and well.

Diagnosis of a malignancy during pregnancy presents a dilemma regarding the work-up and treatment of the patient. This report presents a 42-year-old woman on her 23rd week of pregnancy with multiple enlarging fungating violaceous skin masses. Biopsy of the dominant mass revealed anaplastic large cell lymphoma. Due to the progressive enlargement and increase in number of the masses, the patient was given two cycles of chemotherapy (doxorubicin, vincristine, cyclophosphamide and prednisone) before delivering a live baby boy via spontaneous vaginal delivery, Apgar 9.9, at 37 4/7 weeks. After delivery, she completed four more cycles of treatment. A full-body positron emission tomography scan done 2 months after the last chemotherapy showed no evidence of disease. The patient is doing well with no evidence of disease 9 months after treatment. Her baby is thriving and has no gross deformities and no developmental delays.

Lymphoma is among the five most frequent malignancies during pregnancy while anaplastic large-cell lymphoma (ALCL) is rare, accounting only for 2-3 % of all adult-onset non-Hodgkin lymphomas.

A 23-year-old gravida 1, para 1 presented with puerperal mastitis and septicemia following secondary cesarean section. Mastitis had been present for a week prior to delivery. A CT scan for further diagnostics revealed numerous prominent lymph nodes. Cerebrospinal fluid testing, bone marrow and lymph node biopsy confirmed diagnosis of ALCL. Systemic and intrathecal chemotherapy was initiated, stabilizing the patient's clinical situation. 30 days postpartum (pp.), a cerebral edema was diagnosed responsible for cerebro-venous hypoperfusion. Immediate ventricle drainage and further therapeutic measures revealed no improvement. The patient died 33 days pp.

Puerperal septicemia seemingly caused by mastitis still needs rapid further evaluation if the patient's clinical presentation quickly declines despite antibiotic therapy. Immediate initiation of chemotherapy after confirmation of ALCL is required to increase the therapeutic benefit due to the poor prognosis of ALCL.

At least one in a thousand pregnancies is complicated by cancer and, as the maternal age at pregnancy increases, numbers are growing. If chemotherapy cannot be postponed, both doctors and patients face complex medical and ethical issues. There is a conflict between optimal maternal therapy and fetal wellbeing. Treatment during the first trimester increases the risk of congenital malformations, spontaneous abortions and fetal death. Second and third trimester exposure is less risky, but it can cause intrauterine growth retardation and low birth weight. Other effects on pregnancy after the first trimester include premature birth, stillbirth, impaired functional development, myocardial toxicity and myelosuppression. Counseling and management of these cases are difficult, because literature is mostly represented by case reports or retrospective series while randomized prospective studies or guidelines are lacking. Moreover, personal experience is often scanty due to the rarity of the condition. This article reviews the available data regarding the different aspects of systemic treatment of cancer during pregnancy to help oncologist and obstetricians in counseling their patients and treat them accordingly.

Haematological cancer in pregnancy, although rare, poses a substantial risk to both mother and fetus. Hodgkin's lymphoma is the most common, followed by non-Hodgkin lymphoma and acute leukaemia. Diagnosis of haematological cancers is challenged by an overlap of the disease and gestation-related symptoms and limitations of imaging studies in pregnancy. Data for safety and effectiveness of therapy are scarce and mostly retrospective. This report provides updated guidance for management, focusing on chemotherapy and biological agents. The primary goal of treatment is to preserve the mother's health; hence, pregnancy termination is often advisable at early stages, allowing delivery of adequate therapy. However, at later gestational stages treatment is often feasible. Pregnancy-related hypercoagulability, augmented by cancer, often necessitates thromboprophylaxis. The consequences and complex management of haematological cancer during pregnancy emphasise the need for collaborative research, focusing on basic mechanisms of disease and prospective epidemiological studies.

The management of hematological malignancies during pregnancy is a challenging endeavor, which not only requires technical skills and knowledge by the clinicians but also requires sound clinical judgment and compassion, keeping in mind the patient and family preferences and, ultimately, the wellbeing of the neonate. The incidence of hematological malignancies during pregnancy is rare, ranging from 1 in 1,000 to 1 in 10,000 deliveries, impeding the design and execution of large prospective studies. The purpose of this review is to evaluate the limited existing data and make useful suggestions in the management of acute and chronic leukemias, Hodgkin and non-Hodgkin lymphomas, plasma cell myeloma, and other hematological malignancies, such as myelodysplastic syndromes and hairy cell leukemia, during pregnancy.

We report a case of B-cell lymphoma during pregnancy associated with hemophagocytic syndrome and placental involvement. A 33-year-old Japanese woman developed pancytopenia, hepatosplenomegaly, and a high-grade fever for 2 weeks at 23 weeks of gestation. The demonstration of hemophagocytes in her bone marrow confirmed the diagnosis of hemophagocytic syndrome. She was referred at 25 weeks of gestation for evaluation of hemophagocytic syndrome. The screening for infection and autoimmune disease was negative. Clinical manifestation suggested malignant lymphoma as the underlying cause of hemophagocytic syndrome, but we could not confirm any lymphoma involvement in the bone marrow aspiration. Glucocorticoid therapy did not arrest the hemophagocytic process. Her general status worsened, and reduction of amniotic fluid was noted. At 28 weeks of gestation, we performed a Cesarean section because of fetal distress. Microscopic examination of placental specimen revealed diffuse infiltration of large, atypical lymphoid cells involving the intervillous space. Using immunohistochemical study, we made the diagnosis of B-cell lymphoma. R-CHOP (rituximab/cyclophosphamide/doxorubicin/vincristine/prednisone) chemotherapy was administered on the eighth postpartum day. After 2 cycles of R-CHOP chemotherapy, hematopoiesis became normal and hepatosplenomegaly almost completely disappeared. After 6 cycles of R-CHOP, the patient received autologous peripheral-blood stem cell transplantation, and she is currently in complete remission 1 year after diagnosis. The infant did well, without clinical or laboratory manifestations of malignant lymphoma. In cases with suspected malignancy associated with hemophagocytic syndrome during pregnancy, it is important to verify placental microscopic examination for evaluating the causative disease of hemophagocytic syndrome.

Complete pathologic evaluation of the placenta provides valuable information for perinatal care for the obstetrician, neonatologist, pediatrician, and family. The histopathology of the placenta can answer specific questions about in utero insults, give insight into management of subsequent pregnancies, and provide an assessment of the newborn risk. Placental pathology has been a key litigious informant in inferring timing of insults. Despite these well known advantages of placental pathologic examination, it remains an under-utilized part of perinatal medicine. This stems from a historically under-taught part of surgical and autopsy pathology resulting in inadequate reporting. This review will focus on the utility of the placental examination for fetal and maternal well-being. This review will be restricted to singleton births.

Anaplastic large-cell lymphoma (ALCL) is a rare T-cell lymphoma typically seen in children and young adults. It has been described in numerous sites; however, the breast is one of the least common locations. We herein report a case of ALCL arising in the breast of a 36-yr-old pregnant woman. To our knowledge this is the second such case in the English literature. We would like to highlight the cytologic and histologic features of ALCL, as this case was initially misdiagnosed as a ductal carcinoma. Differential diagnosis with other tumors is also discussed. This case serves to emphasize the importance of the triple test, and the need for correlation of fine-needle aspiration findings with core biopsy findings in breast tumor management.

Hematologic malignancies complicating pregnancy are uncommon, but a delay in diagnosis or treatment can mean the difference between life and death. It is the responsibility of the obstetrician, nurse-midwife, or nurse practitioner to maintain a high index of suspicion when patients present with unexplained lymphadenopathy or protracted constitutional symptoms. Management of these patients requires a multifaceted team from the oncology, pediatrics, and obstetrics services. With most hematologic cancers now requiring multiagent chemotherapy for optimal survival, the patient, her family, and her physicians are often faced with what seems to be a Faustian dilemma. Most infants exposed in utero to multiagent chemotherapy, however, seem to suffer no long-term detrimental consequences.

Anaplastic large cell lymphoma (ALCL) is a well-recognized subtype of non-Hodgkin lymphoma in childhood. Several series report experience with the diagnosis and management of pediatric ALCL, the average age at diagnosis being 8 to 16 years, with a reported range of 1 to 15 years. We present a case of ALCL affecting a 5-month-old infant in whom the diagnosis was confirmed by the nuclear and cytoplasmic immunohistochemical expression of ALK1, in addition to the presence of classical t(2;5)(p23;q35) translocation detected using reverse transcriptase-polymerase chain reaction. This is the youngest case of ALCL thus far reported and hence expands the spectrum of infantile lymphoproliferative disorders.

Pregnancy and leukemia are difficult to manage. Protecting the mother from hemorrhage and infection and the fetus from developmental failure are the main aims. Chronic lymphocytic leukemia (CLL) has been seen very rarely with pregnancy. In this article, the successful labor of a 43-year-old woman with CLL is reported. She was not a candidate for chemotherapy at that time. She was without symptoms when she got pregnant. In the 30th gestational week she was found to have urinary tract infection and preterm labor and she was stabilized. Gestational diabetes and preeclampsia were also determined after that period and managed. The patient was delivered by cesarean section in the 39th gestational week. Cord blood was collected and preserved. No postpartum complication was seen in either the patient or the infant. This is one of the rare cases presenting CLL with pregnancy in the literature.

The variability of tumour responses to chemotherapeutic agents is a topic of major interest in current oncology research. Advances in the knowledge of molecular pathology of cancer make available strategies by which tumour cells can be profiled for their genetic background in order to select anticancer agents that might selectively kill cells in a molecular context that matches the mechanism of action of drugs. The next generation of anticancer treatments might thus be tailored on the basis of the numerous molecular alterations identified in tumour cells of a particular patient. However, to exploit these alterations, it is necessary to understand how they influence the cellular pathways that control the sensitivity or, conversely, resistance to chemotherapeutic agents. The aim of this article is to outline major genetic abnormalities in non-Hodgkin lymphomas that can be used to streamline anticancer drug selection and to underscore the major role of pharmacogenetics, which studies the interactions between genetic background and drug activity, to the prediction of likelihood of response and identification of potential new targets for pharmacological intervention.

The clinicopathological and biological significance of Hodgkin's disease and non-Hodgkin's lymphoma, which are infrequently encountered in women of childbearing age, remains to be clarified. We recently reviewed 4 cases of non-Hodgkin's lymphoma of the T/natural killer (T/NK)-cell phenotype, all of which were associated with pregnancy and characterized by the expression of the cytotoxic granule-associated proteins T-cell intracellular antigen-1 and/or granzyme B. The 4 cases selected had presented between November 1993 and May 1999. The criteria for selection were that the onset of clinical manifestations occurred during pregnancy or within 6 months after delivery. The patients comprised 1 patient with p80/anaplastic lymphoma kinase (ALK)-positive anaplastic large cell lymphoma (ALCL), 1 with p80/ALK-negative ALCL, and 2 with peripheral T/NK-cell lymphomas of unspecified type. The diseases followed aggressive clinical courses: 3 patients died within 6.5 months after diagnosis, and only 1 was still alive with the disease 17 months after diagnosis. The diseases appeared to progress rapidly after delivery. Maternal immunity and hormonal changes during pregnancy may be closely related to the biological behavior of these unusual tumors. This study is, to the best of our knowledge, the first to address pregnancy-associated cytotoxic lymphoma.

Malignant lymphoma of the female genital tract (FGT) is rare. In this study, 5 peripheral T/natural killer (NK)-cell lymphomas (PTCLs) involving the FGT are reported. They include 2 from the uterus and 1 each from ovary, uterus and ovary, and vagina, and were detected between 1996 and 2000. One of the 2 ovarian tumors was bilateral. In all cases, the FGT was the initial site of clinical presentation of disease. Age at presentation ranged from 21 to 52 years (median, 36 years). One case was stage I disease, 2 were stage II, and 2 were stage IV. All 5 tumors were positive for CD3epsilon, and 3 harbored the Epstein-Barr virus, although the detailed immunophenotypic profiles varied. Three were diagnosed as nasal type T/NK-cell lymphoma, 1 as anaplastic large-cell lymphoma (anaplastic lymphoma kinase [ALK]-positive), and 1 as unspecified PTCL of cytotoxic phenotype, according to the forthcoming World Health Organization classification. Four of 5 patients received laparotomy and chemotherapy. Four patients (in stages II and IV) died of disease within 16 months of the initial diagnosis, whereas only 1 patient (in stage I) is alive without disease at 39 months of follow-up. Our experience in this series provided clinically relevant information on diagnosis, treatment, and outcome for extremely rare tumors of the FGT.

The history of a 28-year-old woman with anaplastic large cell lymphoma (ALCL) in the first trimester of her pregnancy is reported. Investigations allowed to diagnose a T-cell CD30 positive ALCL, which appearance is rare during pregnancy. Moreover, the atypical lymphoid cells were found in the peripheral blood and were predominantly small to medium sized with nuclear irregularities and cytoplasmic azurophilic granules, which allowed the hypothesis of leukaemic presentation of a small cell variant ALCL. A variant of the t(2:5)(p23:q35) was found [del(2)(p22)]. The patient died shortly after diagnosis.

We present here a case of B-cell-type mediastinal malignant lymphoma during pregnancy complicated by placental involvement. In this case, some nodular high-echo patterns were recognized in the placenta by ultrasonography. A cesarean section and resection of the mediastinal tumor were performed at 33 weeks and 6 days of gestation due to the deterioration of the dyspnea. A female infant weighing 1,868 g was delivered and she is now a healthy 2-year-old. The mother, however, died of the disease 1 month after surgery, due to progression of the tumor. The placenta showed numerous white firm nodules varying from 3 mm to 3 cm in diameter. The pathologic findings of both the mediastinal tumor and the placenta indicated primary mediastinal (thymic) B-cell lymphoma.

Lymphoma involving the placenta or fetus remains a very rare event. All cases reported to date have shown the lymphoma cells to be of maternal origin in that the tumor cells have preferentially involved the intervillous spaces with sparing of the villi and fetal circulation. We report a novel case of a monoclonal primary placental Epstein-Barr virus (EBV)-associated B-cell lymphoma of fetal origin. The placenta of a 20-week stillborn fetus born to a 19-year-old gravida 1 para 0 woman, presenting with oligohydramnios, showed a large cell infiltrate confined within villi and sparing the intervillous spaces, indicative of preferential involvement of the fetal circulation. Necropsy did not show any other site of involvement by malignant lymphoma or other abnormalities. Immunophenotypic studies showed the tumor cells to be of B-cell phenotype with a relatively high proliferation rate. EBV EBER1 RNA was identified in more than 95% of tumor cells, and polymerase chain reaction studies showed EBV EBNA1 strain type A and wildtype EBV LMP1. Analysis of the immunoglobulin heavy chain by polymerase chain reaction showed a monoclonal B-cell population. In situ hybridization studies using a commercially available probe directed at repeated sequences on the human Y chromosome showed a single intense signal within trophoblastic epithelium and lymphoma cells, indicative of male origin. The mother remains in good health 11 months after delivery.

Massive chronic intervillositis (MCI) is an infrequently recognized placental lesion thought to be of immunologic origin that has been associated with poor fetal outcome. It is characterized by a prominent inflammatory infiltrate in the intervillous space, composed mainly of monocytes and macrophages that can simulate a maternal malignant disorder involving the placenta. The villi are characteristically spared. We report 74 cases of placental malarial infection with morphologic features of MCI. In all cases, the massive inflammatory infiltrate was limited to the intervillous space, which appeared largely obliterated. Increased fibrin deposition and prominent syncytial knots were frequent associated findings. Inflammatory cells were CD45 and CD68 positive, consistent with a monocyte-macrophage population. Some polymorphonuclear leukocytes and scattered T and B lymphocytes were also present. Villi were not inflamed. Malarial pigment was present in all cases, and parasitized maternal erythrocytes were evident in 73 of 74 patients. The histologic pattern of MCI was observed in 17.6% of placentas with malarial parasites. Malarial MCI affected predominantly primigravida women (77%) and was associated with a reduced birth weight, which in 39 (53%) of the infants was less than 2500 g, and a low gestational age. None of the infants with placentas with MCI died in the early neonatal period. Morphologic changes of MCI are seen in a significant percentage of placentas with malarial infection, especially in primigravida women, and are associated with a low birth weight. Malarial infection should therefore be considered in the differential diagnosis of massive intervillous infiltrates.